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This provides a candidate somatic-cell contribution to the ovarian phenotype, but it is not yet a demonstrated lesion in an intact human ovary and does not exclude a germ-cell-autonomous contribution.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Turner_Syndrome.html#pathophysiology-granulosa-cell-differentiation-and-cell-cycle-dysfunction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ATurner_Syndrome:pathophysiology:Accelerated%20Ovarian%20Germ%20Cell%20Attrition%20and%20Follicular%20Atresia","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Accelerated Ovarian Germ Cell Attrition and Follicular Atresia","description":"Germ cells are laid down in the Turner ovary but are then lost at an accelerated rate through follicular atresia, so the process is depletion rather than failure of germ-cell formation. 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The state has not yet been demonstrated in intact human Turner ovaries and its connection to a specific X-dosage-sensitive gene remains unknown.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Turner_Syndrome.html#pathophysiology-granulosa-cell-apelin-apj-signaling-dysfunction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"}],"edges":[{"id":"model-link:1:model:kb/disorders/Turner_Syndrome.yaml:45,X patient-derived iPSC granulosa-like cells","source_id":"model:kb/disorders/Turner_Syndrome.yaml:45,X patient-derived iPSC granulosa-like cells","target_id":"node:disorder%3ATurner_Syndrome:pathophysiology:Granulosa-Cell%20Differentiation%20and%20Cell-Cycle%20Dysfunction","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[1]","label":"Partially Recapitulates","directed":false,"relationship":"PARTIALLY_RECAPITULATES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"The system reproduces reduced granulosa marker expression and abnormal cell-cycle progression associated with 45,X donor cells.\n","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ATurner_Syndrome:5:0","source_id":"node:disorder%3ATurner_Syndrome:pathophysiology:Granulosa-Cell%20Apelin%2FAPJ%20Signaling%20Dysfunction","target_id":"node:disorder%3ATurner_Syndrome:pathophysiology:Granulosa-Cell%20Differentiation%20and%20Cell-Cycle%20Dysfunction","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[5].downstream[0]","label":"Indirectly causes (known intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_KNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Known Intermediates","description":"Apelin ligands and downstream Akt activation partly restored cell-cycle progression and granulosa marker expression, placing impaired signaling upstream of the model's cellular defect without establishing that it is the only cause.\n","intermediate_mechanisms":["APJ signaling through Akt/PKB and CTPS2 regulation"],"hypothesis_groups":["granulosa_apelin_model"],"evidence_count":1},{"id":"causal:disorder%3ATurner_Syndrome:6:0","source_id":"node:disorder%3ATurner_Syndrome:pathophysiology:Granulosa-Cell%20Differentiation%20and%20Cell-Cycle%20Dysfunction","target_id":"node:disorder%3ATurner_Syndrome:pathophysiology:Accelerated%20Ovarian%20Germ%20Cell%20Attrition%20and%20Follicular%20Atresia","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[6].downstream[0]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"The study proposes that defective granulosa-cell support during ovarian development contributes to early oocyte loss. 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The study frames its own result as suggesting the line \"may serve as a useful model\", which is the appropriate strength.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[],"biological_processes":[],"pathways":[],"genes":[],"chemicals":[],"readouts":[],"evidence":[],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:ALG2-Congenital_Disorder_of_Glycosylation","model_node_id":"model:kb/disorders/ALG2-Congenital_Disorder_of_Glycosylation.yaml:661W photoreceptor cell line expressing ALG2 p.Arg251Leu","focus_node_id":"node:disorder%3AALG2-Congenital_Disorder_of_Glycosylation:pathophysiology:ALG2%20Alpha-1%2C3%2F1%2C6-Mannosyltransferase%20Deficiency","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/ALG2-congenital_disorder_of_glycosylation.html#pathograph","nodes":[{"id":"model:kb/disorders/ALG2-Congenital_Disorder_of_Glycosylation.yaml:661W photoreceptor cell line expressing ALG2 p.Arg251Leu","kind":"experimental_model","kind_label":"NAM model","label":"661W photoreceptor cell line expressing ALG2 p.Arg251Leu","description":"An immortalised mouse retinal cell line transfected with the homozygous p.Arg251Leu allele found in the Argentinean patients, used to test whether that allele reduces ALG2 protein and glycan levels in a photoreceptor-like context.","url":"https://dismech.monarchinitiative.org/pages/disorders/ALG2-congenital_disorder_of_glycosylation.html#experimental-model-661w-photoreceptor-cell-line-expressing-alg2-p-arg251leu","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AALG2-Congenital_Disorder_of_Glycosylation:pathophysiology:ALG2%20Alpha-1%2C3%2F1%2C6-Mannosyltransferase%20Deficiency","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"ALG2 Alpha-1,3/1,6-Mannosyltransferase Deficiency","description":"Biallelic ALG2 variants reduce the abundance or catalytic activity of the ER membrane enzyme that adds both the alpha-1,3- and the alpha-1,6-mannose to Man1GlcNAc2-PP-dolichol. 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p.Arg251Leu), which encodes the enzyme α-1,3-mannosyltransferase.","explanation":"Defines the model and the allele it carries."}],"evidence_text":["In this study, we utilized the 661W cell line to explore the molecular consequences of a homozygous variant in the ALG2 gene (c.752G>T; p.Arg251Leu), which encodes the enzyme α-1,3-mannosyltransferase.","Defines the model and the allele it carries."],"evidence_status":"Evidence recorded","metadata_completeness":50,"metadata_present":["Model category","NAMO class","Modeled mechanism","Publication","Evidence"],"metadata_missing":["Organism","Anatomy","Cell type","Cell source","Culture system"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/ALG2-Congenital_Disorder_of_Glycosylation.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/ALG2-Congenital_Disorder_of_Glycosylation.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/ALG2-congenital_disorder_of_glycosylation.html#experimental-model-661w-photoreceptor-cell-line-expressing-alg2-p-arg251leu","source_anchor":"experimental-model-661w-photoreceptor-cell-line-expressing-alg2-p-arg251leu"},{"id":"model:kb/disorders/Alpers-Huttenlocher_Syndrome.yaml:A449T mouse embryonic fibroblast mtDNA recovery","name":"A449T mouse embryonic fibroblast mtDNA recovery","description":"Baseline mtDNA content was not reduced, but mutant cells accumulated more replicating foci and failed to recover mtDNA during the observed interval after ethidium-bromide depletion. 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their causal sequence is proposed rather than isolated experimentally.","intermediate_mechanisms":[],"hypothesis_groups":["ser348leu_epithelial_clefting"],"evidence_count":1},{"id":"causal:disorder%3ABaraitser-Winter_Cerebrofrontofacial_Syndrome:8:0","source_id":"node:disorder%3ABaraitser-Winter_Cerebrofrontofacial_Syndrome:pathophysiology:Reduced%20Epithelial%20Cell%20Migration","target_id":"node:disorder%3ABaraitser-Winter_Cerebrofrontofacial_Syndrome:phenotype:Orofacial%20Cleft","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[8].downstream[0]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"Impaired epithelial behavior is proposed to contribute to clefting for ACTB Ser348Leu; the cell assay does not directly demonstrate human palatal fusion.","intermediate_mechanisms":[],"hypothesis_groups":["ser348leu_epithelial_clefting"],"evidence_count":1}]}}],"mechanism_names":["Reduced ACTB-PFN1 Association","Impaired Junctional ACTB Localization","Reduced Epithelial Cell Migration"],"relationships":["Recapitulates"],"fidelities":["Not Specified"],"biological_scales":["Molecular","Cellular"],"system_context_sources":["Linked mechanism biological scale"],"modeled_system_labels":["Molecular","Cellular"],"biological_process_terms":[],"biological_processes":[],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":[],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"url:https://ir.library.osaka-u.ac.jp/repo/ouka/all/103591//HumMolGenet_33_22_1975.pdf","reference_url":null,"reference_title":"https://ir.library.osaka-u.ac.jp/repo/ouka/all/103591//HumMolGenet_33_22_1975.pdf","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"MDCK cells (JCRB cell bank: IFO50071) were cultured in αMEM with nucleosides (Gibco) and 10% FBS (Gibco) under standard conditions.","explanation":"The epithelial system is an established canine kidney cell line with transfected human ACTB constructs."},{"reference":"url:https://ir.library.osaka-u.ac.jp/repo/ouka/all/103591//HumMolGenet_33_22_1975.pdf","reference_url":null,"reference_title":"https://ir.library.osaka-u.ac.jp/repo/ouka/all/103591//HumMolGenet_33_22_1975.pdf","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"In contrast, the mutant ACTB (p.S348L) did not show an intense signal at the cell junction but rather showed uniform expression in the cytoplasm","explanation":"This result is specifically from MDCK cells overexpressing GFP-tagged ACTB."},{"reference":"url:https://ir.library.osaka-u.ac.jp/repo/ouka/all/103591//HumMolGenet_33_22_1975.pdf","reference_url":null,"reference_title":"https://ir.library.osaka-u.ac.jp/repo/ouka/all/103591//HumMolGenet_33_22_1975.pdf","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We detected similar expression levels between the mutant (p.S348L) ... while the signal of PFN1 was noticeably reduced in the sample with mutant ACTB (p.S348L)","explanation":"Tsujimoto et al. (2024), Compromised actin dynamics underlie the orofacial cleft in Baraitser-Winter Cerebrofrontofacial Syndrome with a variant in ACTB: GFP pulldown from MDCK extracts mixed with exogenous PFN1 shows reduced association. This is not a measured binding constant."},{"reference":"url:https://ir.library.osaka-u.ac.jp/repo/ouka/all/103591//HumMolGenet_33_22_1975.pdf","reference_url":null,"reference_title":"https://ir.library.osaka-u.ac.jp/repo/ouka/all/103591//HumMolGenet_33_22_1975.pdf","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We observed that the mutant ACTB (p.S348L) -overexpressing cells displayed slower migration over time than the wild-type ACTB-overexpressing cells","explanation":"The MDCK assay measures closure of a defined cell-free gap after removal of a silicone insert. It is a surrogate for epithelial behavior, not direct measurement of patient palatal fusion."}],"evidence_text":["MDCK cells (JCRB cell bank: IFO50071) were cultured in αMEM with nucleosides (Gibco) and 10% FBS (Gibco) under standard conditions.","In contrast, the mutant ACTB (p.S348L) did not show an intense signal at the cell junction but rather showed uniform expression in the cytoplasm","We detected similar expression levels between the mutant (p.S348L) ... while the signal of PFN1 was noticeably reduced in the sample with mutant ACTB (p.S348L)","We observed that the mutant ACTB (p.S348L) -overexpressing cells displayed slower migration over time than the wild-type ACTB-overexpressing cells","The epithelial system is an established canine kidney cell line with transfected human ACTB constructs.","This result is specifically from MDCK cells overexpressing GFP-tagged ACTB.","Tsujimoto et al. (2024), Compromised actin dynamics underlie the orofacial cleft in Baraitser-Winter Cerebrofrontofacial Syndrome with a variant in ACTB: GFP pulldown from MDCK extracts mixed with exogenous PFN1 shows reduced association. This is not a measured binding constant.","The MDCK assay measures closure of a defined cell-free gap after removal of a silicone insert. It is a surrogate for epithelial behavior, not direct measurement of patient palatal fusion."],"evidence_status":"Evidence recorded","metadata_completeness":80,"metadata_present":["Model category","NAMO class","Organism","Cell source","Culture system","Modeled mechanism","Publication","Evidence"],"metadata_missing":["Anatomy","Cell type"],"dataset_context":"Available in same entry","context_dataset_ids":["dataset:https://data.ghga.de/dataset/ghgad98802067102801","dataset:https://www.ebi.ac.uk/biostudies/sourcedata/studies/s-scdt-10_1038-s44319-025-00647-7"],"candidate_dataset_ids":[],"source_path":"kb/disorders/Baraitser-Winter_Cerebrofrontofacial_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Baraitser-Winter_Cerebrofrontofacial_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Baraitser-Winter_Cerebrofrontofacial_Syndrome.html#experimental-model-actb-ser348leu-mdck-epithelial-model","source_anchor":"experimental-model-actb-ser348leu-mdck-epithelial-model"},{"id":"model:kb/disorders/LDLR-Related_Familial_Hypercholesterolemia.yaml:Activity-normalized prime editing saturation screen of LDLR coding variants","name":"Activity-normalized prime editing saturation screen of LDLR coding variants","description":"Pooled prime-editing screen installing 5,184 LDLR coding variants at the endogenous locus in human cells and scoring each for LDL-cholesterol uptake, with a genotypic outcome reporter paired to every guide so scores can be normalized for editing efficiency. It is the saturation counterpart of the one-variant-at-a-time heterologous assay above: instead of ranking a handful of alleles it maps the whole coding series onto a continuous activity scale, and because the variant sits at the endogenous locus it also catches splice-altering coding changes that complementary-DNA constructs cannot express.","notes":"The screen also reports a cluster of gain-of-function variants in ligand-binding repeat 5, at least some of which raise LDL uptake through increased apolipoprotein B interaction. Those alleles are not part of this disease - they are the mirror image of it - and are noted here only because they come from the same experiment and bear on therapeutic genome editing.","context_id":"disorder:LDLR-Related_Familial_Hypercholesterolemia","context_kind":"Disorder","disease_name":"LDLR-Related Familial Hypercholesterolemia","disease_synonyms":["Hypercholesterolemia, familial, 1","FHCL1","Familial hypercholesterolemia type 1","LDL receptor disorder","LDL receptor deficiency","Hyperlipoproteinemia type 2A","Familial hypercholesterolemic xanthomatosis","Autosomal dominant hypercholesterolemia 1"],"disease_term":{"id":"MONDO:0007750","label":"hypercholesterolemia, familial, 1","display_label":"LDLR-Related Familial Hypercholesterolemia","url":"http://purl.obolibrary.org/obo/MONDO_0007750"},"experimental_model_type":"CELL_LINE","experimental_model_type_label":"Cell line","namo_type":"namo:CellLineModel","declared_namo_class_name":null,"namo_class_name":"CellLineModel","namo_class_label":"Cell Line Model","namo_description":"A model system based on immortalized cell lines that can be maintained in culture indefinitely. Examples: HepG2, A549, Caco-2, etc.","namo_docs_url":"https://monarch-initiative.github.io/namo/elements/CellLineModel/","namo_ontology_url":"https://w3id.org/monarch-initiative/namo/CellLineModel","namo_mapping_basis":"Safe mapping from DisMech category","namo_class_in_schema":true,"namo_schema_status":"Defined in NAMO schema used for this build","modality":"Cellular system","organism":{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},"organism_label":"Homo sapiens","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[{"id":"UBERON:0002107","label":"liver","display_label":"liver","url":"http://purl.obolibrary.org/obo/UBERON_0002107"}],"linked_anatomy_labels":["liver"],"anatomy":[{"id":"UBERON:0002107","label":"liver","display_label":"liver","url":"http://purl.obolibrary.org/obo/UBERON_0002107"}],"anatomy_labels":["liver"],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[{"id":"CL:0000182","label":"hepatocyte","display_label":"hepatocyte","url":"http://purl.obolibrary.org/obo/CL_0000182"}],"linked_cell_type_labels":["hepatocyte"],"cell_types":[{"id":"CL:0000182","label":"hepatocyte","display_label":"hepatocyte","url":"http://purl.obolibrary.org/obo/CL_0000182"}],"cell_type_labels":["hepatocyte"],"conditions":[],"cell_source":"Human cells carrying prime-edited LDLR at the endogenous locus","source_category":"Immortalized / cell line","culture_system":"Pooled two-dimensional culture with fluorescence-based LDL uptake sorting","publication":"PMID:42677454","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42677454","mechanisms":[{"target":"Reduced Functional Hepatic LDL Receptor Activity","target_url":"https://dismech.monarchinitiative.org/pages/disorders/LDLR-Related_Familial_Hypercholesterolemia.html#pathophysiology-reduced-functional-hepatic-ldl-receptor-activity","relationship":"MEASURES","relationship_label":"Measures","fidelity":"MODERATE","fidelity_label":"Moderate","description":"Measures residual LDL uptake for each of 5,184 coding variants, turning the receptor-activity axis this node represents into a per-allele quantity that separates known pathogenic from known benign variants and tracks LDL-C in an independent human cohort.","limitations":"Uptake is a single composite readout, so unlike the stepwise flow cytometry assay it does not resolve which step of the receptor itinerary an allele breaks and therefore does not by itself assign a receptor class. It covers coding variants only, leaving promoter changes and exon-level deletions untouched, and the functional score is calibrated as evidence toward classification rather than as a diagnosis in its own right.","biological_scale":"CELLULAR","anatomy":[{"id":"UBERON:0002107","label":"liver","display_label":"liver","url":"http://purl.obolibrary.org/obo/UBERON_0002107"}],"cell_types":[{"id":"CL:0000182","label":"hepatocyte","display_label":"hepatocyte","url":"http://purl.obolibrary.org/obo/CL_0000182"}],"biological_processes":[{"id":"GO:0006898","label":"receptor-mediated endocytosis","display_label":"receptor-mediated endocytosis","url":"http://purl.obolibrary.org/obo/GO_0006898"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Per-variant LDL-cholesterol uptake score","description":null,"target":"Reduced Functional Hepatic LDL Receptor Activity","direction":"DECREASED","interpretation":"A continuous activity score per allele, anchored by the separation of pathogenic from benign ClinVar variants and by concordance with measured LDL-C in carriers.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:42677454","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/42677454","reference_title":"LDLR Variant Classification Through Activity-Normalized Prime Editing Screening.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The resulting scores capture a continuous spectrum of functional effects, robustly separate pathogenic versus benign ClinVar variants, and show concordance with LDL-C levels in UK Biobank participants.","explanation":"Reports both the score itself and the two external anchors that make it interpretable as receptor activity."}],"notes":null}],"evidence":[{"reference":"PMID:42677454","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/42677454","reference_title":"LDLR Variant Classification Through Activity-Normalized Prime Editing Screening.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We developed the first activity-normalized prime editing screening pipeline to measure the impact of 5184 LDLR coding variants on LDL-cholesterol (LDL-C) uptake.","explanation":"Describes the assay and its scale, which is what makes it informative for the receptor-activity node across the allelic series rather than for one allele."},{"reference":"PMID:42677454","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/42677454","reference_title":"LDLR Variant Classification Through Activity-Normalized Prime Editing Screening.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"prime editing uniquely detects splice-altering coding variants missed by cDNA-based screens and pathogenicity predictors, revealing an advantage of endogenous variant installation","explanation":"The specific advantage of editing the endogenous locus, and the reason this model is not redundant with construct-based assays of the same node."},{"reference":"PMID:42677454","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/42677454","reference_title":"LDLR Variant Classification Through Activity-Normalized Prime Editing Screening.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The resulting scores capture a continuous spectrum of functional effects, robustly separate pathogenic versus benign ClinVar variants, and show concordance with LDL-C levels in UK Biobank participants.","explanation":"Reports both the score itself and the two external anchors that make it interpretable as receptor activity."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:LDLR-Related_Familial_Hypercholesterolemia","model_node_id":"model:kb/disorders/LDLR-Related_Familial_Hypercholesterolemia.yaml:Activity-normalized prime editing saturation screen of LDLR coding variants","focus_node_id":"node:disorder%3ALDLR-Related_Familial_Hypercholesterolemia:pathophysiology:Reduced%20Functional%20Hepatic%20LDL%20Receptor%20Activity","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/LDLR-Related_Familial_Hypercholesterolemia.html#pathograph","nodes":[{"id":"model:kb/disorders/LDLR-Related_Familial_Hypercholesterolemia.yaml:Activity-normalized prime editing saturation screen of LDLR coding variants","kind":"experimental_model","kind_label":"NAM model","label":"Activity-normalized prime editing saturation screen of LDLR coding variants","description":"Pooled prime-editing screen installing 5,184 LDLR coding variants at the endogenous locus in human cells and scoring each for LDL-cholesterol uptake, with a genotypic outcome reporter paired to every guide so scores can be normalized for editing efficiency. It is the saturation counterpart of the one-variant-at-a-time heterologous assay above: instead of ranking a handful of alleles it maps the whole coding series onto a continuous activity scale, and because the variant sits at the endogenous locus it also catches splice-altering coding changes that complementary-DNA constructs cannot express.","url":"https://dismech.monarchinitiative.org/pages/disorders/LDLR-Related_Familial_Hypercholesterolemia.html#experimental-model-activity-normalized-prime-editing-saturation-screen-of-ldlr-coding-variants","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALDLR-Related_Familial_Hypercholesterolemia:pathophysiology:Reduced%20Functional%20Hepatic%20LDL%20Receptor%20Activity","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced Functional Hepatic LDL Receptor Activity","description":"The convergence node of the allelic series. Whichever step is broken - synthesis, ER export, ligand binding, internalization, or recycling - the measurable output is the same: fewer LDL particles cleared per unit time by the hepatocyte. Functional assays report this as a single quantity (percentage of wild-type LDL uptake), which is why class assignment and residual activity are recorded separately: the class says *where* the itinerary breaks, the residual activity says *how much* capacity survives. Null alleles are conventionally under about 2% of normal activity, though trial protocols have operationalized \"null\" at thresholds as high as 15%.","url":"https://dismech.monarchinitiative.org/pages/disorders/LDLR-Related_Familial_Hypercholesterolemia.html#pathophysiology-reduced-functional-hepatic-ldl-receptor-activity","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALDLR-Related_Familial_Hypercholesterolemia:pathophysiology:Absent%20LDL%20Receptor%20Synthesis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Absent LDL Receptor Synthesis","description":"The class 1 (null, receptor-negative) branch. No immunodetectable LDL receptor protein is made, because the allele deletes the promoter, produces no mRNA, or produces mRNA that yields no protein. This is the most severe branch and the one with the least therapeutic room: there is no receptor to upregulate. In clinical trials of homozygous disease it is operationalized as \"null-null\" or receptor-negative status.","url":"https://dismech.monarchinitiative.org/pages/disorders/LDLR-Related_Familial_Hypercholesterolemia.html#pathophysiology-absent-ldl-receptor-synthesis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALDLR-Related_Familial_Hypercholesterolemia:pathophysiology:Defective%20Clustering%20in%20Clathrin-Coated%20Pits","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Defective Clustering in Clathrin-Coated Pits","description":"The class 4 (internalization-defective) branch. The cytoplasmic tail of the LDL receptor carries the signal that concentrates it in clathrin-coated pits; a change there leaves a receptor that is expressed and binds LDL normally but is distributed diffusely over the surface and enters the cell slowly. The founding example is patient J.D., whose receptor carries a tyrosine-to-cysteine substitution at residue 807. Because the LDLRAP1/ARH adaptor serves this same step, the recessive LDLRAP1 disease is the phenocopy of this branch acting in trans.","url":"https://dismech.monarchinitiative.org/pages/disorders/LDLR-Related_Familial_Hypercholesterolemia.html#pathophysiology-defective-clustering-in-clathrin-coated-pits","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALDLR-Related_Familial_Hypercholesterolemia:pathophysiology:Defective%20Endosomal%20Ligand%20Release%20and%20Receptor%20Recycling","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Defective Endosomal Ligand Release and Receptor Recycling","description":"The class 5 (recycling-defective) branch. Binding and internalization are intact, but the receptor fails to release LDL when the endosome acidifies, so receptor and ligand traffic together to the lysosome and the receptor is consumed rather than returned to the surface. Each receptor therefore makes one round trip instead of many, and functional clearance capacity collapses even though synthesis is normal. This is also the step that PCSK9 subverts pharmacologically, which is why PCSK9-directed drugs raise receptor abundance in patients who still have recyclable receptor.","url":"https://dismech.monarchinitiative.org/pages/disorders/LDLR-Related_Familial_Hypercholesterolemia.html#pathophysiology-defective-endosomal-ligand-release-and-receptor-recycling","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALDLR-Related_Familial_Hypercholesterolemia:pathophysiology:Defective%20LDL%20Binding%20at%20the%20Hepatocyte%20Surface","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Defective LDL Binding at the Hepatocyte Surface","description":"The class 3 (binding-defective) branch. Receptor reaches the surface in normal numbers but binds apoB-100-containing LDL with reduced affinity. Changes typically fall in the cysteine-rich ligand-binding repeats or in the EGF-precursor homology domain that holds them in a binding-competent conformation. This is the receptor-side mirror of the ligand-side defect curated in Familial_Defective_Apolipoprotein_B-100 - the same handshake fails, from the other side.","url":"https://dismech.monarchinitiative.org/pages/disorders/LDLR-Related_Familial_Hypercholesterolemia.html#pathophysiology-defective-ldl-binding-at-the-hepatocyte-surface","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALDLR-Related_Familial_Hypercholesterolemia:pathophysiology:Impaired%20ER-to-Golgi%20Transport%20of%20the%20LDL%20Receptor","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired ER-to-Golgi Transport of the LDL Receptor","description":"The class 2 (transport-defective) branch. The receptor is synthesized but misfolds and is retained in the endoplasmic reticulum rather than being further glycosylated in the Golgi and delivered to the surface. Retention may be complete (class 2a) or partial (class 2b), and partial retention leaves residual surface receptor - which matters therapeutically, because residual receptor is what receptor-directed drugs act on.","url":"https://dismech.monarchinitiative.org/pages/disorders/LDLR-Related_Familial_Hypercholesterolemia.html#pathophysiology-impaired-er-to-golgi-transport-of-the-ldl-receptor","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALDLR-Related_Familial_Hypercholesterolemia:pathophysiology:Impaired%20Receptor-Mediated%20Clearance%20of%20Plasma%20LDL","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Receptor-Mediated Clearance of Plasma LDL","description":"Reduced hepatic receptor capacity lengthens the residence time of apoB-100-containing LDL and IDL in plasma. The defect is specific to the receptor's ligands: HDL clearance is unaffected, which is why the biochemical phenotype is an isolated elevation of LDL rather than a generalized dyslipidemia.","url":"https://dismech.monarchinitiative.org/pages/disorders/LDLR-Related_Familial_Hypercholesterolemia.html#pathophysiology-impaired-receptor-mediated-clearance-of-plasma-ldl","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALDLR-Related_Familial_Hypercholesterolemia:pathophysiology:Residual%20Receptor%20Activity%20Gates%20Receptor-Dependent%20LDL%20Lowering","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Residual Receptor Activity Gates Receptor-Dependent LDL Lowering","description":"The pharmacogenetic node, and the reason the allelic series is clinically actionable rather than merely descriptive. Statins lower intracellular cholesterol and thereby induce more LDL receptor; PCSK9 antibodies and inclisiran prevent or reduce PCSK9-mediated receptor degradation. Both families of drugs work by putting *more* receptor on the hepatocyte surface, so both require a receptor that can be made and can function. The genotype-stratified evidence below is for a PCSK9 antibody: in the two receptor-negative (null-null) homozygotes studied there was nothing to induce and the response was absent, while in receptor-defective homozygotes there was residual receptor and the response was preserved. Whether statins behave the same way in receptor-negative disease has not been tested here - the two null patients in that trial were already on stable statin therapy at enrolment - and the mechanisms differ (statins act transcriptionally on receptor synthesis, PCSK9-directed agents post-translationally on receptor degradation and recycling), so the statin/PCSK9 asymmetry is carried as an open question in the residual_ldlr_activity_response_threshold discussion rather than asserted. LDLR-independent agents - the MTP inhibitor lomitapide, the ANGPTL3 antibody evinacumab, and lipoprotein apheresis - bypass the receptor entirely and retain effect in null-null disease. 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This experiment does not establish the mechanism of seizures in patients or a temporal ordering with synaptic abnormalities.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Recessive_Spinocerebellar_Ataxia_20.html#pathophysiology-reduced-cortical-neuron-excitability","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3AAutosomal_Recessive_Spinocerebellar_Ataxia_20:pathophysiology:SNX14%20Loss%20of%20Function","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"SNX14 Loss of Function","description":"Biallelic pathogenic variants reduce normal SNX14 function. 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(A1004S)","Intracellular calcium transient"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:28088328","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/28088328","reference_title":"Altered myocyte contractility and calcium homeostasis in alpha-myosin heavy chain point mutations linked to familial dilated cardiomyopathy.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Despite a shared association with DCM, the P830L and A1004S αMHC mutations alter myocyte contractility in completely different ways while at the same preserving peak intracellular calcium.","explanation":"The authors' own conclusion, and the reason this entry declines to curate a single MYH6 contractile defect."},{"reference":"PMID:28088328","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/28088328","reference_title":"Altered myocyte 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Furthermore, PKD1-/- tubules present primary cilia defects when dilated.","explanation":"Supports a restrained mechanistic link between human organoid phenotypes and the ciliary and tubular morphogenesis abnormalities represented in PKD pathophysiology."}]}],"findings_text":["ADPKD kidney organoids reproduce renal cyst formation from genetically relevant human renal epithelium","Tubular epithelial organoids also capture early PKD1-linked morphogenesis and ciliary defects relevant to cyst initiation"],"evidence":[{"reference":"PMID:32819584","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/32819584","reference_title":"A novel ADPKD model using kidney organoids derived from disease-specific human iPSCs.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Here, we report a novel ADPKD model using kidney organoids derived from disease-specific human induced pluripotent stem cells (hiPSCs).","explanation":"Supports this as a first-class human organoid model for ADPKD."},{"reference":"PMID:32819584","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/32819584","reference_title":"A novel ADPKD model using kidney organoids derived from disease-specific human iPSCs.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Importantly, we found that kidney organoids differentiated from gene-edited heterozygous PKD1-mutant as well as ADPKD patient-derived hiPSCs can reproduce renal cysts.","explanation":"Shows that both engineered and patient-derived human iPSC kidney organoids recapitulate the core cystic phenotype of ADPKD."},{"reference":"PMID:40140667","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40140667","reference_title":"PKD1 mutation perturbs morphogenesis in tubular epithelial organoids derived from human pluripotent stem cells.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"PKD1 null (PKD1-/-) organoids spontaneously develop dilated tubules, recapitulating early ADPKD cystogenesis. 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Multiple cellular sources and altered synthesis/regulation contribute. Urinary LTE4 is a systemic readout, not a specific measure of one cell type or a stand-alone diagnostic test.","url":"https://dismech.monarchinitiative.org/pages/disorders/Aspirin-Exacerbated_Respiratory_Disease.html#pathophysiology-increased-cysteinyl-leukotriene-availability","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAspirin-Exacerbated_Respiratory_Disease:pathophysiology:Increased%20Platelet-Leukocyte%20Adherence","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Increased Platelet-Leukocyte Adherence","description":"Increased platelet attachment to circulating myeloid leukocytes and colocalization in nasal polyps are observed in AERD. The platelet-intrinsic LTC4 synthase activity was not higher than in aspirin-tolerant controls. Enhanced adhesion-receptor expression on platelet-associated cells occurred across groups, not uniquely in AERD.","url":"https://dismech.monarchinitiative.org/pages/disorders/Aspirin-Exacerbated_Respiratory_Disease.html#pathophysiology-increased-platelet-leukocyte-adherence","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Aspirin-Exacerbated_Respiratory_Disease.yaml:AERD granulocyte-platelet ex vivo preparations","source_id":"model:kb/disorders/Aspirin-Exacerbated_Respiratory_Disease.yaml:AERD granulocyte-platelet ex vivo preparations","target_id":"node:disorder%3AAspirin-Exacerbated_Respiratory_Disease:pathophysiology:Enhanced%20Transcellular%20Cysteinyl%20Leukotriene%20Synthesis","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Measures","directed":false,"relationship":"MEASURES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"Platelet removal lowers fMLP-stimulated cysteinyl leukotriene release.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AAspirin-Exacerbated_Respiratory_Disease:6:0","source_id":"node:disorder%3AAspirin-Exacerbated_Respiratory_Disease:pathophysiology:Enhanced%20Transcellular%20Cysteinyl%20Leukotriene%20Synthesis","target_id":"node:disorder%3AAspirin-Exacerbated_Respiratory_Disease:pathophysiology:Increased%20Cysteinyl%20Leukotriene%20Availability","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[6].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Increased transcellular synthesis contributes to the available cysteinyl leukotriene pool; 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Re-expression of wild-type TRAPPC12 rescues Golgi fragmentation; rescue of the separate transport and mitotic readouts was not reported.","notes":null,"context_id":"disorder:TRAPPC12-Related_Encephalopathy","context_kind":"Disorder","disease_name":"TRAPPC12-Related Encephalopathy","disease_synonyms":["PEBAS","early-onset progressive encephalopathy-hearing loss-pons hypoplasia-brain atrophy syndrome","early-onset progressive encephalopathy with brain atrophy and spasticity","TRAPPC12-related childhood encephalopathy","TRAPPC12-related disorder","TTC15-related encephalopathy"],"disease_term":{"id":"MONDO:0044696","label":"early-onset progressive encephalopathy-hearing loss-pons hypoplasia-brain atrophy syndrome","display_label":"TRAPPC12-related encephalopathy","url":"http://purl.obolibrary.org/obo/MONDO_0044696"},"experimental_model_type":"PRIMARY_CELL_CULTURE","experimental_model_type_label":"Primary-cell culture","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},"organism_label":"Homo sapiens","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":"Primary dermal fibroblasts from affected individuals and controls","source_category":"Primary / biopsy-derived","culture_system":"Fibroblast monolayer with immunoblotting, Golgi morphology, cargo-transport, complementation, and live-cell mitotic-timing assays","publication":"PMID:28777934","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/28777934","mechanisms":[{"target":"Biallelic TRAPPC12 Dysfunction","target_url":"https://dismech.monarchinitiative.org/pages/disorders/TRAPPC12-Related_Encephalopathy.html#pathophysiology-biallelic-trappc12-dysfunction","relationship":"RECAPITULATES","relationship_label":"Recapitulates","fidelity":"HIGH","fidelity_label":"High","description":"The affected-person lines directly reproduce absence of full-length TRAPPC12 for both the homozygous and compound-heterozygous genotypes.","limitations":"Fibroblast protein abundance does not by itself define the consequences in neural lineages or the residual activity of every allele.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[],"biological_processes":[],"pathways":[],"genes":[{"id":"hgnc:24284","label":"TRAPPC12","display_label":"TRAPPC12","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/24284"}],"chemicals":[],"readouts":[],"evidence":[{"reference":"url:https://pmc.ncbi.nlm.nih.gov/articles/PMC5544387/","reference_url":null,"reference_title":"Mutations in TRAPPC12 Manifest in Progressive Childhood Encephalopathy and Golgi Dysfunction - PMC","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"As expected for the homozygous truncating variant in 1:II-8, western blot analysis failed to detect any full-length...Unexpectedly, the full-length protein was also absent in 2:II-1 and 2:II-4","explanation":"Directly demonstrates the proximal protein-loss phenotype in all three founding fibroblast lines."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:TRAPPC12-Related_Encephalopathy","model_node_id":"model:kb/disorders/TRAPPC12-Related_Encephalopathy.yaml:Affected-person fibroblast Golgi and secretory-transport model","focus_node_id":"node:disorder%3ATRAPPC12-Related_Encephalopathy:pathophysiology:Biallelic%20TRAPPC12%20Dysfunction","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/TRAPPC12-Related_Encephalopathy.html#pathograph","nodes":[{"id":"model:kb/disorders/TRAPPC12-Related_Encephalopathy.yaml:Affected-person fibroblast Golgi and secretory-transport model","kind":"experimental_model","kind_label":"NAM model","label":"Affected-person fibroblast Golgi and secretory-transport model","description":"Primary fibroblasts from all three founding individuals lack full-length TRAPPC12, reproduce fragmented Golgi morphology and delayed ER-to-Golgi transport, and show prolonged prophase-to-anaphase timing. Re-expression of wild-type TRAPPC12 rescues Golgi fragmentation; rescue of the separate transport and mitotic readouts was not reported.","url":"https://dismech.monarchinitiative.org/pages/disorders/TRAPPC12-Related_Encephalopathy.html#experimental-model-affected-person-fibroblast-golgi-and-secretory-transport-model","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ATRAPPC12-Related_Encephalopathy:pathophysiology:Biallelic%20TRAPPC12%20Dysfunction","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Biallelic TRAPPC12 Dysfunction","description":"Biallelic pathogenic variants in TRAPPC12 (also known as TTC15 or TRAMM) perturb protein abundance or function. Full-length protein was absent from fibroblasts of all three founding individuals, who carried homozygous or compound-heterozygous frameshift/missense genotypes. A later homozygous Phe227Val fibroblast study likewise found absent or markedly reduced mature protein but only mild organelle abnormalities. Separately, compound-heterozygous c.954del and c.1677+5G>A variants were found in a family with recurrent fetal hydrocephalus; the former causes premature termination and the latter was shown to alter splicing. A surviving child with a homozygous frameshift means complete loss of detectable full-length protein should not be described as uniformly embryonic lethal.","url":"https://dismech.monarchinitiative.org/pages/disorders/TRAPPC12-Related_Encephalopathy.html#pathophysiology-biallelic-trappc12-dysfunction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ATRAPPC12-Related_Encephalopathy:phenotype:Agenesis%20of%20corpus%20callosum","kind":"phenotype","kind_label":"Phenotype","label":"Agenesis of corpus callosum","description":"One founding individual had complete callosal agenesis; the other two had severe thinning with absent posterior segments.","url":"https://dismech.monarchinitiative.org/pages/disorders/TRAPPC12-Related_Encephalopathy.html#phenotype-agenesis-of-corpus-callosum","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ATRAPPC12-Related_Encephalopathy:phenotype:Cerebellar%20hypoplasia","kind":"phenotype","kind_label":"Phenotype","label":"Cerebellar hypoplasia","description":"Mild cerebellar hypoplasia was recorded in two of three founding individuals; this developmental finding is distinct from later-reported cerebellar atrophy.","url":"https://dismech.monarchinitiative.org/pages/disorders/TRAPPC12-Related_Encephalopathy.html#phenotype-cerebellar-hypoplasia","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ATRAPPC12-Related_Encephalopathy:pathophysiology:Delayed%20ER-to-Golgi%20Transport","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Delayed ER-to-Golgi Transport","description":"Founding affected-person fibroblasts show delayed protein transport from the endoplasmic reticulum to and through the Golgi. 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The 2025 Phe227Val fibroblast study used Nile-red lipid-vesicle distribution rather than a matched ER-to-Golgi cargo assay, so it cannot establish whether this atomic transport phenotype is present or absent for that genotype.","url":"https://dismech.monarchinitiative.org/pages/disorders/TRAPPC12-Related_Encephalopathy.html#pathophysiology-delayed-er-to-golgi-transport","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ATRAPPC12-Related_Encephalopathy:pathophysiology:Golgi%20Fragmentation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Golgi Fragmentation","description":"Fibroblasts from affected individuals show a fragmented Golgi apparatus and re-expression of wild-type TRAPPC12 rescues that morphology in the founding lines. Phe227Val fibroblasts show milder Golgi disorganization, so severity is genotype-dependent. Rescue has not been shown for the separately measured cargo-transport delay.","url":"https://dismech.monarchinitiative.org/pages/disorders/TRAPPC12-Related_Encephalopathy.html#pathophysiology-golgi-fragmentation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ATRAPPC12-Related_Encephalopathy:phenotype:Hydrocephalus","kind":"phenotype","kind_label":"Phenotype","label":"Hydrocephalus","description":"At the most severe (fetal/lethal) end of the TRAPPC12 spectrum, compound heterozygous variants were associated with recurrent fetal hydrocephaly and pregnancy loss; the cited report describes a possible developmental mechanism.","url":"https://dismech.monarchinitiative.org/pages/disorders/TRAPPC12-Related_Encephalopathy.html#phenotype-hydrocephalus","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ATRAPPC12-Related_Encephalopathy:phenotype:Hypoplasia%20of%20the%20corpus%20callosum","kind":"phenotype","kind_label":"Phenotype","label":"Hypoplasia of the corpus callosum","description":"Severe thinning with absence of posterior callosal segments occurred in two founding individuals; complete agenesis is curated separately.","url":"https://dismech.monarchinitiative.org/pages/disorders/TRAPPC12-Related_Encephalopathy.html#phenotype-hypoplasia-of-the-corpus-callosum","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ATRAPPC12-Related_Encephalopathy:phenotype:Hypoplasia%20of%20the%20pons","kind":"phenotype","kind_label":"Phenotype","label":"Hypoplasia of the pons","description":"Pontine (brainstem) hypoplasia is part of the characteristic imaging signature.","url":"https://dismech.monarchinitiative.org/pages/disorders/TRAPPC12-Related_Encephalopathy.html#phenotype-hypoplasia-of-the-pons","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ATRAPPC12-Related_Encephalopathy:phenotype:Hypoplastic%20optic%20chiasm","kind":"phenotype","kind_label":"Phenotype","label":"Hypoplastic optic chiasm","description":"A small optic chiasm was recorded in two of three founding MRIs.","url":"https://dismech.monarchinitiative.org/pages/disorders/TRAPPC12-Related_Encephalopathy.html#phenotype-hypoplastic-optic-chiasm","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ATRAPPC12-Related_Encephalopathy:pathophysiology:Prolonged%20Mitotic%20Progression","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Prolonged Mitotic Progression","description":"Fibroblasts from all three founding individuals took significantly longer from prophase to anaphase than control fibroblasts. 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The abstract reports marker expression and secreted matrix proteins, not deposited fibrillar collagen, matrix stiffening or stellate cell contraction.","biological_scale":"CELLULAR","anatomy":[{"id":"UBERON:0002107","label":"liver","display_label":"Liver","url":"http://purl.obolibrary.org/obo/UBERON_0002107"}],"cell_types":[{"id":"CL:0000632","label":"hepatic stellate cell","display_label":"Hepatic Stellate Cell","url":"http://purl.obolibrary.org/obo/CL_0000632"},{"id":"CL:0000186","label":"myofibroblast cell","display_label":"Myofibroblast","url":"http://purl.obolibrary.org/obo/CL_0000186"}],"biological_processes":[{"id":"GO:0007179","label":"transforming growth factor beta receptor signaling pathway","display_label":"TGF-beta Receptor Signaling","url":"http://purl.obolibrary.org/obo/GO_0007179"},{"id":"GO:0032964","label":"collagen biosynthetic process","display_label":"Collagen 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of the fibrosis marker induction measured in the stellate compartment."}],"notes":null},{"name":"Extracellular matrix remodeling proteins (Pro-Collagen 1A1, CTGF)","description":null,"target":"Hepatic Stellate Cell Activation","direction":"INCREASED","interpretation":"Elevated pro-collagen and CTGF establish that the activated stellate cells produce matrix, the downstream consequence this node feeds.","biological_processes":[{"id":"GO:0030198","label":"extracellular matrix organization","display_label":"extracellular matrix organization","url":"http://purl.obolibrary.org/obo/GO_0030198"}],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:40754287","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40754287","reference_title":"A high-throughput microphysiological system to quantify key events leading to liver fibrosis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Extracellular matrix remodeling was confirmed by elevated Pro-Collagen 1A1 and 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TGF-beta signals through SMAD2/3 phosphorylation to upregulate collagen synthesis and inhibit matrix degradation.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Liver_Cirrhosis.html#pathophysiology-tgf-beta-signaling-in-fibrogenesis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Liver_Cirrhosis.yaml:Akura Twin 384-well liver fibrosis microphysiological system (HepaRG/THP-1 and hTERT-HSC microtissues)","source_id":"model:kb/disorders/Liver_Cirrhosis.yaml:Akura Twin 384-well liver fibrosis microphysiological system (HepaRG/THP-1 and hTERT-HSC microtissues)","target_id":"node:disorder%3ALiver_Cirrhosis:pathophysiology:Hepatic%20Stellate%20Cell%20Activation","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"TGF-beta 1 drives the hTERT-HSC compartment through the defining transition of this node, inducing the myofibroblast marker program and the matrix products that follow from it.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ALiver_Cirrhosis:9:0","source_id":"node:disorder%3ALiver_Cirrhosis:pathophysiology:Hepatic%20Pro-Inflammatory%20Mediator%20Release","target_id":"node:disorder%3ALiver_Cirrhosis:pathophysiology:Hepatic%20Stellate%20Cell%20Activation","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[9].downstream[0]","label":"Causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":null,"causal_link_type_label":null,"description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ALiver_Cirrhosis:3:0","source_id":"node:disorder%3ALiver_Cirrhosis:pathophysiology:Hepatic%20Stellate%20Cell%20Activation","target_id":"node:disorder%3ALiver_Cirrhosis:pathophysiology:Excessive%20Hepatic%20ECM%20Deposition","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[3].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Activated stellate-cell-derived myofibroblasts are the effector cells that synthesize and deposit the excessive extracellular matrix; this edge is the step by which the central fibrogenic event proceeds into matrix accumulation.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ALiver_Cirrhosis:2:0","source_id":"node:disorder%3ALiver_Cirrhosis:pathophysiology:IL-11%20Signalling%20in%20Hepatic%20Stellate%20Cells","target_id":"node:disorder%3ALiver_Cirrhosis:pathophysiology:Hepatic%20Stellate%20Cell%20Activation","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[0]","label":"Causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":null,"causal_link_type_label":null,"description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ALiver_Cirrhosis:7:0","source_id":"node:disorder%3ALiver_Cirrhosis:pathophysiology:TGF-beta%20Signaling%20in%20Fibrogenesis","target_id":"node:disorder%3ALiver_Cirrhosis:pathophysiology:Hepatic%20Stellate%20Cell%20Activation","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[7].downstream[0]","label":"Causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":null,"causal_link_type_label":null,"description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0}]}},{"target":"Kupffer Cell Activation","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Liver_Cirrhosis.html#pathophysiology-kupffer-cell-activation","relationship":"PARTIALLY_RECAPITULATES","relationship_label":"Partially Recapitulates","fidelity":"LOW","fidelity_label":"Low","description":"A monocytic compartment co-cultured with the hepatocyte microtissues supplies the inflammatory arm of the fibrotic cascade and is activated alongside it.","limitations":"THP-1 is a circulating monocytic leukemia line, not a resident Kupffer cell, and the system has no sinusoidal endothelial or lymphocyte compartment. 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PAI-1 is a fibrinolysis inhibitor rather than one of the cytokines (TGF-beta, IL-6, TNF-alpha) this node's description names, so it stands in for the mediator-release event rather than measuring it directly.","biological_scale":"TISSUE","anatomy":[{"id":"UBERON:0002107","label":"liver","display_label":"Liver","url":"http://purl.obolibrary.org/obo/UBERON_0002107"}],"cell_types":[],"biological_processes":[{"id":"GO:0006954","label":"inflammatory response","display_label":"Inflammatory Response","url":"http://purl.obolibrary.org/obo/GO_0006954"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"PAI-1 protein in hepatocyte-monocyte co-culture","description":null,"target":"Hepatic Pro-Inflammatory Mediator Release","direction":"INCREASED","interpretation":"PAI-1 rose most in the co-cultured wells, which is the readout that distinguishes the hepatocyte-monocyte interaction from hepatocytes alone.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:40754287","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40754287","reference_title":"A high-throughput microphysiological system to quantify key events leading to liver fibrosis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"PAI-1 protein levels increased following treatment with TGF-β1, particularly in HepaRG-THP-1 co-cultures.","explanation":"Reports the PAI-1 measurement and that it depended on the presence of the monocytic compartment."}],"notes":null}],"evidence":[{"reference":"PMID:40754287","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40754287","reference_title":"A high-throughput microphysiological system to quantify key events leading to liver fibrosis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We studied fibrosis progression by seeding HepaRG microtissues (MTs), with or without THP-1 cells in alpha wells and hepatic stellate cell (hTERT-HSC) MTs in beta wells.","explanation":"Establishes that a monocytic compartment is present in co-culture, enabling measurement of the mediator-release readout below."},{"reference":"PMID:40754287","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40754287","reference_title":"A high-throughput microphysiological system to quantify key events leading to liver fibrosis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"PAI-1 protein levels increased following treatment with TGF-β1, particularly in HepaRG-THP-1 co-cultures.","explanation":"Reports the PAI-1 measurement and that it depended on the presence of the monocytic compartment."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Liver_Cirrhosis","model_node_id":"model:kb/disorders/Liver_Cirrhosis.yaml:Akura Twin 384-well liver fibrosis microphysiological system (HepaRG/THP-1 and hTERT-HSC microtissues)","focus_node_id":"node:disorder%3ALiver_Cirrhosis:pathophysiology:Hepatic%20Pro-Inflammatory%20Mediator%20Release","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Liver_Cirrhosis.html#pathograph","nodes":[{"id":"model:kb/disorders/Liver_Cirrhosis.yaml:Akura Twin 384-well liver fibrosis microphysiological system (HepaRG/THP-1 and hTERT-HSC microtissues)","kind":"experimental_model","kind_label":"NAM model","label":"Akura Twin 384-well liver fibrosis microphysiological system (HepaRG/THP-1 and hTERT-HSC microtissues)","description":"High-throughput microphysiological system built on a 384-well microplate of 168 interconnected well pairs. 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A non-animal New Approach Methodology built to quantify the key events of the liver fibrosis Adverse Outcome Pathway under TGF-beta 1, methotrexate and acetaminophen challenge.","url":"https://dismech.monarchinitiative.org/pages/disorders/Liver_Cirrhosis.html#experimental-model-akura-twin-384-well-liver-fibrosis-microphysiological-system-heparg-thp-1-and-htert-hsc-microtissues","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALiver_Cirrhosis:pathophysiology:Hepatic%20Pro-Inflammatory%20Mediator%20Release","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Hepatic Pro-Inflammatory Mediator Release","description":"Activated Kupffer cells and recruited macrophages release profibrogenic cytokines and chemokines such as TGF-beta, IL-6, and TNF-alpha that activate hepatic stellate cells and perpetuate the fibrotic response.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Liver_Cirrhosis.html#pathophysiology-hepatic-pro-inflammatory-mediator-release","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALiver_Cirrhosis:pathophysiology:Hepatic%20Stellate%20Cell%20Activation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Hepatic Stellate Cell Activation","description":"Quiescent stellate cells transform into myofibroblasts, producing excessive collagen and extracellular matrix. This is the central event in liver fibrosis.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Liver_Cirrhosis.html#pathophysiology-hepatic-stellate-cell-activation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALiver_Cirrhosis:pathophysiology:Kupffer%20Cell%20Activation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Kupffer Cell Activation","description":"Hepatocyte death triggers activation of Kupffer cells and recruitment of inflammatory cells including macrophages.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Liver_Cirrhosis.html#pathophysiology-kupffer-cell-activation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALiver_Cirrhosis:pathophysiology:TGF-beta%20Signaling%20in%20Fibrogenesis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"TGF-beta Signaling in Fibrogenesis","description":"Transforming growth factor beta is the master profibrogenic cytokine driving hepatic stellate cell activation and extracellular matrix production. TGF-beta signals through SMAD2/3 phosphorylation to upregulate collagen synthesis and inhibit matrix degradation.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Liver_Cirrhosis.html#pathophysiology-tgf-beta-signaling-in-fibrogenesis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:2:model:kb/disorders/Liver_Cirrhosis.yaml:Akura Twin 384-well liver fibrosis microphysiological system (HepaRG/THP-1 and hTERT-HSC microtissues)","source_id":"model:kb/disorders/Liver_Cirrhosis.yaml:Akura Twin 384-well liver fibrosis microphysiological system (HepaRG/THP-1 and hTERT-HSC microtissues)","target_id":"node:disorder%3ALiver_Cirrhosis:pathophysiology:Hepatic%20Pro-Inflammatory%20Mediator%20Release","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[2]","label":"Partially Recapitulates","directed":false,"relationship":"PARTIALLY_RECAPITULATES","fidelity":"LOW","causal_link_type":null,"causal_link_type_label":null,"description":"The same monocytic compartment's secreted PAI-1 is read as an output of the co-culture's mediator-release program, distinct from the marker induction that signals the compartment's own activation.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ALiver_Cirrhosis:9:0","source_id":"node:disorder%3ALiver_Cirrhosis:pathophysiology:Hepatic%20Pro-Inflammatory%20Mediator%20Release","target_id":"node:disorder%3ALiver_Cirrhosis:pathophysiology:Hepatic%20Stellate%20Cell%20Activation","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[9].downstream[0]","label":"Causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":null,"causal_link_type_label":null,"description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ALiver_Cirrhosis:9:1","source_id":"node:disorder%3ALiver_Cirrhosis:pathophysiology:Hepatic%20Pro-Inflammatory%20Mediator%20Release","target_id":"node:disorder%3ALiver_Cirrhosis:pathophysiology:TGF-beta%20Signaling%20in%20Fibrogenesis","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[9].downstream[1]","label":"Causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":null,"causal_link_type_label":null,"description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ALiver_Cirrhosis:8:0","source_id":"node:disorder%3ALiver_Cirrhosis:pathophysiology:Kupffer%20Cell%20Activation","target_id":"node:disorder%3ALiver_Cirrhosis:pathophysiology:Hepatic%20Pro-Inflammatory%20Mediator%20Release","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[8].downstream[0]","label":"Causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":null,"causal_link_type_label":null,"description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0}]}},{"target":"Hepatocyte Injury and Death","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Liver_Cirrhosis.html#pathophysiology-hepatocyte-injury-and-death","relationship":"PARTIALLY_RECAPITULATES","relationship_label":"Partially Recapitulates","fidelity":"MODERATE","fidelity_label":"Moderate","description":"Hepatotoxicant and TGF-beta 1 challenge injures the HepaRG compartment, supplying the initiating injury this node describes.","limitations":"Injury is inferred from loss of albumin synthesis. The abstract reports no direct cell-death measurement - no caspase, LDH release or viability assay - so the death half of this node is not demonstrated.","biological_scale":"CELLULAR","anatomy":[{"id":"UBERON:0002107","label":"liver","display_label":"Liver","url":"http://purl.obolibrary.org/obo/UBERON_0002107"}],"cell_types":[{"id":"CL:0000182","label":"hepatocyte","display_label":"Hepatocyte","url":"http://purl.obolibrary.org/obo/CL_0000182"}],"biological_processes":[],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Albumin production under TGF-beta 1, methotrexate and acetaminophen","description":null,"target":"Hepatocyte Injury and Death","direction":"DECREASED","interpretation":"Falling albumin synthesis is the model's index of hepatocellular injury, and responds to both a profibrogenic cytokine and two hepatotoxic drugs.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:40754287","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40754287","reference_title":"A high-throughput microphysiological system to quantify key events leading to liver fibrosis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Transforming growth factor beta 1 (TGF-β1), methotrexate (MTX) and acetaminophen (APAP) reduced albumin production, indicating hepatocellular injury.","explanation":"Reports the albumin measurement, its direction, and the authors' reading of it as hepatocellular injury."}],"notes":null}],"evidence":[{"reference":"PMID:40754287","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40754287","reference_title":"A high-throughput microphysiological system to quantify key events leading to liver fibrosis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Transforming growth factor beta 1 (TGF-β1), methotrexate (MTX) and acetaminophen (APAP) reduced albumin production, indicating hepatocellular injury.","explanation":"Supports treating the hepatocyte compartment as an injury model, since three separate challenges each reduced its synthetic function."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Liver_Cirrhosis","model_node_id":"model:kb/disorders/Liver_Cirrhosis.yaml:Akura Twin 384-well liver fibrosis microphysiological system (HepaRG/THP-1 and hTERT-HSC microtissues)","focus_node_id":"node:disorder%3ALiver_Cirrhosis:pathophysiology:Hepatocyte%20Injury%20and%20Death","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Liver_Cirrhosis.html#pathograph","nodes":[{"id":"model:kb/disorders/Liver_Cirrhosis.yaml:Akura Twin 384-well liver fibrosis microphysiological system (HepaRG/THP-1 and hTERT-HSC microtissues)","kind":"experimental_model","kind_label":"NAM model","label":"Akura Twin 384-well liver fibrosis microphysiological system (HepaRG/THP-1 and hTERT-HSC microtissues)","description":"High-throughput microphysiological system built on a 384-well microplate of 168 interconnected well pairs. 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The adduction is a measured quantity rather than an asserted step: covalent binding of 14C from labelled CCl4 is quantified against oxygen tension, added glutathione, cytochrome P-450 induction and CCl4 dose, and the protein-bound label localises to the cytochrome P-450 apoprotein mass range.","url":"https://dismech.monarchinitiative.org/pages/disorders/Liver_Cirrhosis.html#pathophysiology-reactive-metabolite-formation-and-covalent-protein-adduction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:3:model:kb/disorders/Liver_Cirrhosis.yaml:Akura Twin 384-well liver fibrosis microphysiological system (HepaRG/THP-1 and hTERT-HSC microtissues)","source_id":"model:kb/disorders/Liver_Cirrhosis.yaml:Akura Twin 384-well liver fibrosis microphysiological system (HepaRG/THP-1 and hTERT-HSC microtissues)","target_id":"node:disorder%3ALiver_Cirrhosis:pathophysiology:Hepatocyte%20Injury%20and%20Death","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[3]","label":"Partially Recapitulates","directed":false,"relationship":"PARTIALLY_RECAPITULATES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"Hepatotoxicant and TGF-beta 1 challenge injures the HepaRG compartment, supplying the initiating injury this node describes.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ALiver_Cirrhosis:1:0","source_id":"node:disorder%3ALiver_Cirrhosis:pathophysiology:Hepatocyte%20Injury%20and%20Death","target_id":"node:disorder%3ALiver_Cirrhosis:pathophysiology:Kupffer%20Cell%20Activation","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[0]","label":"Causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":null,"causal_link_type_label":null,"description":"Dying and stressed hepatocytes are the trigger for the liver's resident-macrophage response; this edge carries that initiating step, separate from the mediator-release event it leads to.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ALiver_Cirrhosis:0:0","source_id":"node:disorder%3ALiver_Cirrhosis:pathophysiology:Reactive%20Metabolite%20Formation%20and%20Covalent%20Protein%20Adduction","target_id":"node:disorder%3ALiver_Cirrhosis:pathophysiology:Hepatocyte%20Injury%20and%20Death","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[0]","label":"Indirectly causes (known intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_KNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Known Intermediates","description":"Covalent adduction is one of several cooperating consequences of radical formation that together kill the hepatocyte; the cited review is explicit that no single one of them is the sole cause, which is why the edge is typed as having known omitted intermediates rather than DIRECT.","intermediate_mechanisms":["Lipid peroxidation of membrane polyunsaturated fatty acids","Loss of cellular calcium sequestration and homeostasis","Reactive aldehyde (4-hydroxynonenal) adduction of functional proteins"],"hypothesis_groups":[],"evidence_count":1}]}},{"target":"TGF-beta Signaling in Fibrogenesis","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Liver_Cirrhosis.html#pathophysiology-tgf-beta-signaling-in-fibrogenesis","relationship":"PERTURBS","relationship_label":"Perturbs","fidelity":"MODERATE","fidelity_label":"Moderate","description":"TGF-beta 1 is applied exogenously as the driving stimulus of the model, so this node is manipulated rather than reproduced.","limitations":"Recombinant TGF-beta 1 is added directly to the medium in place of the endogenous, injury-driven, latent-TGF-beta activation route. The abstract reports downstream marker responses rather than SMAD2/3 phosphorylation, so the signalling step itself is not measured.","biological_scale":"MOLECULAR","anatomy":[{"id":"UBERON:0002107","label":"liver","display_label":"Liver","url":"http://purl.obolibrary.org/obo/UBERON_0002107"}],"cell_types":[{"id":"CL:0000632","label":"hepatic stellate cell","display_label":"Hepatic Stellate Cell","url":"http://purl.obolibrary.org/obo/CL_0000632"}],"biological_processes":[{"id":"GO:0007179","label":"transforming growth factor beta receptor signaling pathway","display_label":"TGF-beta Receptor Signaling","url":"http://purl.obolibrary.org/obo/GO_0007179"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Downstream response to exogenous TGF-beta 1 challenge","description":null,"target":"TGF-beta Signaling in Fibrogenesis","direction":"INCREASED","interpretation":"Applying TGF-beta 1 raises the fibrosis marker program in the stellate compartment, showing the pathway is intact and drivable in this system.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:40754287","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40754287","reference_title":"A high-throughput microphysiological system to quantify key events leading to liver fibrosis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"In hTERT-HSCs, TGF-β1 also induced expression of fibrosis markers (ACTA2, COL1A1, COL3A1 and FN1) and increased stress fibers and fibronectin expression.","explanation":"Shows that exogenous TGF-beta 1 challenge produces the expected downstream fibrogenic response."}],"notes":null}],"evidence":[{"reference":"PMID:40754287","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40754287","reference_title":"A high-throughput microphysiological system to quantify key events leading to liver fibrosis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"In hTERT-HSCs, TGF-β1 also induced expression of fibrosis markers (ACTA2, COL1A1, COL3A1 and FN1) and increased stress fibers and fibronectin expression.","explanation":"Establishes TGF-beta 1 as the applied perturbation whose downstream consequences the model reads out."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Liver_Cirrhosis","model_node_id":"model:kb/disorders/Liver_Cirrhosis.yaml:Akura Twin 384-well liver fibrosis microphysiological system (HepaRG/THP-1 and hTERT-HSC microtissues)","focus_node_id":"node:disorder%3ALiver_Cirrhosis:pathophysiology:TGF-beta%20Signaling%20in%20Fibrogenesis","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Liver_Cirrhosis.html#pathograph","nodes":[{"id":"model:kb/disorders/Liver_Cirrhosis.yaml:Akura Twin 384-well liver fibrosis microphysiological system (HepaRG/THP-1 and hTERT-HSC microtissues)","kind":"experimental_model","kind_label":"NAM model","label":"Akura Twin 384-well liver fibrosis microphysiological system (HepaRG/THP-1 and hTERT-HSC microtissues)","description":"High-throughput microphysiological system built on a 384-well microplate of 168 interconnected well pairs. 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A non-animal New Approach Methodology built to quantify the key events of the liver fibrosis Adverse Outcome Pathway under TGF-beta 1, methotrexate and acetaminophen challenge.","url":"https://dismech.monarchinitiative.org/pages/disorders/Liver_Cirrhosis.html#experimental-model-akura-twin-384-well-liver-fibrosis-microphysiological-system-heparg-thp-1-and-htert-hsc-microtissues","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALiver_Cirrhosis:pathophysiology:TGF-beta%20Signaling%20in%20Fibrogenesis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"TGF-beta Signaling in Fibrogenesis","description":"Transforming growth factor beta is the master profibrogenic cytokine driving hepatic stellate cell activation and extracellular matrix production. 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fibrosis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"enables high-throughput modeling of liver fibrosis, mimicking the key events of the liver fibrosis AOP","explanation":"The authors' own summary claim that the platform reproduces the key events of liver fibrosis, of which stellate activation is the central one."},{"reference":"PMID:40754287","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40754287","reference_title":"A high-throughput microphysiological system to quantify key events leading to liver fibrosis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"In hTERT-HSCs, TGF-β1 also induced expression of fibrosis markers (ACTA2, COL1A1, COL3A1 and FN1) and increased stress fibers and fibronectin expression.","explanation":"Reports the direction and identity of the fibrosis marker induction measured in the stellate compartment."},{"reference":"PMID:40754287","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40754287","reference_title":"A high-throughput microphysiological system to quantify key events leading to liver fibrosis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Extracellular matrix remodeling was confirmed by elevated Pro-Collagen 1A1 and CTGF protein levels upon TGF-β1 treatment.","explanation":"Reports the matrix-remodeling protein measurements and their direction."},{"reference":"PMID:40754287","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40754287","reference_title":"A high-throughput microphysiological system to quantify key events leading to liver fibrosis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We studied fibrosis progression by seeding HepaRG microtissues (MTs), with or without THP-1 cells in alpha wells and hepatic stellate cell (hTERT-HSC) MTs in beta wells.","explanation":"Establishes that a monocytic compartment is deliberately included and can be compared against its absence."},{"reference":"PMID:40754287","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40754287","reference_title":"A high-throughput microphysiological system to quantify key events leading to liver fibrosis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"TGF-β1 activated THP-1, increasing ALOX5AP, TREM2, and TGF-β1 mRNA expression.","explanation":"Names the activation markers measured in the monocytic compartment and their direction."},{"reference":"PMID:40754287","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40754287","reference_title":"A high-throughput microphysiological system to quantify key events leading to liver fibrosis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"PAI-1 protein levels increased following treatment with TGF-β1, particularly in HepaRG-THP-1 co-cultures.","explanation":"Reports the PAI-1 measurement and that it depended on the presence of the monocytic compartment."},{"reference":"PMID:40754287","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40754287","reference_title":"A high-throughput microphysiological system to quantify key events leading to liver fibrosis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Transforming growth factor beta 1 (TGF-β1), methotrexate (MTX) and acetaminophen (APAP) reduced albumin production, indicating hepatocellular injury.","explanation":"Supports treating the hepatocyte compartment as an injury model, since three separate challenges each reduced its synthetic function."}],"evidence_text":["enables high-throughput modeling of liver fibrosis, mimicking the key events of the liver fibrosis AOP","In hTERT-HSCs, TGF-β1 also induced expression of fibrosis markers (ACTA2, COL1A1, COL3A1 and FN1) and increased stress fibers and fibronectin expression.","Extracellular matrix remodeling was confirmed by elevated Pro-Collagen 1A1 and CTGF protein levels upon TGF-β1 treatment.","We studied fibrosis progression by seeding HepaRG microtissues (MTs), with or without THP-1 cells in alpha wells and hepatic stellate cell (hTERT-HSC) MTs in beta wells.","TGF-β1 activated THP-1, increasing ALOX5AP, TREM2, and TGF-β1 mRNA expression.","PAI-1 protein levels increased following treatment with TGF-β1, particularly in HepaRG-THP-1 co-cultures.","Transforming growth factor beta 1 (TGF-β1), methotrexate (MTX) and acetaminophen (APAP) reduced albumin production, indicating hepatocellular injury.","The authors' own summary claim that the platform reproduces the key events of liver fibrosis, of which stellate activation is the central one.","Reports the direction and identity of the fibrosis marker induction measured in the stellate compartment.","Reports the matrix-remodeling protein measurements and their direction.","Establishes that a monocytic compartment is deliberately included and can be compared against its absence.","Names the activation markers measured in the monocytic 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increased glycosylation upon GLM101 treatment, although this increase was subtle compared to PMM2-CDG and ALG2-CDG","explanation":"Documents the partial biochemical response in ALG11 cells."},{"reference":"PMID:38733638","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38733638","reference_title":"Liposome-encapsulated mannose-1-phosphate therapy improves global N-glycosylation in different congenital disorders of glycosylation.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"GLM101 has not been demonstrated to cross the blood-brain barrier","explanation":"Limits translation of the cell result to neurological treatment."},{"reference":"PMID:38733638","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38733638","reference_title":"Liposome-encapsulated mannose-1-phosphate therapy improves global N-glycosylation in different congenital disorders of glycosylation.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Although the change in high mannose glycans bearing peptides in ALG11-CDG was subtle, all the 87 high mannose glycopeptides with more than 1.5-fold change contained Man6 or higher glycan composition.","explanation":"Direct ALG11-specific glycoproteomic result; glycopeptides are measurements, not independent patients."}],"evidence_text":["Finally, we included the fibroblasts of two individuals with ALG11-CDG, who had features of mild to severe developmental delay, speech delay, infantile seizures and progressive microcephaly","| P7 | 10/F | ALG11 | c.932C>T/c.932C>T | p.P311L/p.P311L |","| P8 | 13/F | ALG11 | c.163A>G/c.163A>G | p.T55A/p.T55A |","The ALG11-deficient fibroblasts also exhibited an increased glycosylation upon GLM101 treatment, although this increase was subtle compared to PMM2-CDG and ALG2-CDG","GLM101 has not been demonstrated to cross the blood-brain barrier","Although the change in high mannose glycans bearing peptides in ALG11-CDG was subtle, all the 87 high mannose glycopeptides with more than 1.5-fold change 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The finding is not universal in individual patients — the 2024 Mexican case had normal coagulation tests.","url":"https://dismech.monarchinitiative.org/pages/disorders/ALG2-congenital_disorder_of_glycosylation.html#pathophysiology-hepatic-and-coagulation-glycoprotein-dysfunction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AALG2-Congenital_Disorder_of_Glycosylation:phenotype:Iris%20coloboma","kind":"phenotype","kind_label":"Phenotype","label":"Iris coloboma","description":"Coloboma of the iris was present in the index patient and is listed among the recurrent ophthalmological features of the disorder.","url":"https://dismech.monarchinitiative.org/pages/disorders/ALG2-congenital_disorder_of_glycosylation.html#phenotype-iris-coloboma","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AALG2-Congenital_Disorder_of_Glycosylation:pathophysiology:Neurodevelopmental%20and%20Myelination%20Failure","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Neurodevelopmental and Myelination Failure","description":"The classic multisystem form is dominated by central nervous system disease: global developmental delay with regression, intractable seizures including infantile spasms, and hypomyelination on imaging. 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glycopeptides bearing Man6 and higher glycans and a decrease in Man5 and smaller glycan moieties, suggesting that GLM101 helps in the formation of mature glycoforms.","Establishes that ALG2-CDG patient cells were among those tested.","The measured glycoproteomic shift in ALG2-CDG cells."],"evidence_status":"Evidence recorded","metadata_completeness":40,"metadata_present":["Model category","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Organism","Anatomy","Cell type","Cell source","Culture system"],"dataset_context":"None recorded in same 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The flagship in vivo model of thin-filament HCM and the only model in this entry that reproduces the whole-organ, whole-organism course: early concentric hypertrophy with fibrosis and atrial enlargement, diastolic dysfunction, increased myofilament calcium sensitivity, and death between four and five months.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_3.html#experimental-model-alpha-tm180-transgenic-mouse-tpm1-glu180gly","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_3:pathophysiology:Alpha-Tropomyosin%20Thin%20Filament%20Regulatory%20Defect","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Alpha-Tropomyosin Thin Filament Regulatory Defect","description":"TPM1 encodes alpha-tropomyosin, a rod-shaped coiled-coil dimer that polymerises head-to-tail along the actin thin filament and, in concert with the troponin complex, occupies the blocked, closed, or open azimuthal position that determines whether myosin can engage actin. Disease-associated missense substitutions are scattered along the molecule - in the N-terminal overlap/troponin T binding region (Arg21Leu, Gly3Arg, Glu62Gln, Gln68Arg), in the central period 4/5 region that contacts actin (Asp175Asn, Glu180Gly, Glu192Lys), and in the C-terminal region (Ser215Leu, Asp219Val, Asp254Gly) - and act by altering tropomyosin flexibility, its azimuthal positioning on actin, or its interactions with troponin, rather than by abolishing the protein. This is the primary cardiomyocyte insult of CMH3.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_3.html#pathophysiology-alpha-tropomyosin-thin-filament-regulatory-defect","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_3:pathophysiology:Divergent%20Non-Hypertrophic%20Remodeling%20Phenotypes","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Divergent Non-Hypertrophic Remodeling Phenotypes","description":"Not every TPM1 variant produces hypertrophy. The same gene causes dilated, restrictive, and left ventricular noncompaction cardiomyopathy, and compound-heterozygous TPM1 genotypes have produced restrictive disease in a child whose singly heterozygous relatives had diastolic dysfunction and HCM. Paired mechanistic study of E62Q (hypertrophic) and E54K (dilated) attributes the divergence to which physical property of tropomyosin the substitution perturbs. This node is included because it constrains how a TPM1 finding may be interpreted clinically, not because it is part of the CMH3 causal chain.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_3.html#pathophysiology-divergent-non-hypertrophic-remodeling-phenotypes","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_3:pathophysiology:Increased%20Myofilament%20Calcium%20Buffering%20and%20Calcium-Dependent%20Signaling","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Increased Myofilament Calcium Buffering and Calcium-Dependent Signaling","description":"Because the mutant thin filament binds calcium more tightly, more of the cytosolic calcium transient is sequestered on the myofilaments. Diastolic calcium rises and reuptake slows; compensatory changes in sodium/calcium exchange, SERCA2 activity, and ryanodine-receptor leak follow, driven by CaMKII phosphorylation. The altered calcium environment chronically engages the calcineurin/NFAT and ERK pathways that transcriptionally program cardiomyocyte hypertrophy, and also creates a substrate for triggered arrhythmia.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_3.html#pathophysiology-increased-myofilament-calcium-buffering-and-calcium-dependent-signaling","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_3:pathophysiology:Loss%20of%20Crossbridge%20Inhibition%20and%20Increased%20Myofilament%20Calcium%20Sensitivity","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Loss of Crossbridge Inhibition and Increased Myofilament Calcium Sensitivity","description":"Mutant alpha-tropomyosin is more flexible and sits less stably in the inhibitory (blocked/closed) position on actin, so the thin filament fails to keep myosin switched off. The measurable consequences are a left-shift in the calcium dependence of filament sliding, residual actomyosin activity at low calcium, and loss of the normal inhibition of sliding in relaxing conditions. Different alleles reach this end state by different routes - S215L and D219V principally by destabilizing the blocked state, E192K by permitting residual crossbridge activity even while overall calcium sensitivity falls - which is why calcium sensitivity alone is an incomplete description of the lesion.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_3.html#pathophysiology-loss-of-crossbridge-inhibition-and-increased-myofilament-calcium-sensitivity","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Hypertrophic_Cardiomyopathy_3.yaml:Alpha-TM180 transgenic mouse (TPM1 Glu180Gly)","source_id":"model:kb/disorders/Hypertrophic_Cardiomyopathy_3.yaml:Alpha-TM180 transgenic mouse (TPM1 Glu180Gly)","target_id":"node:disorder%3AHypertrophic_Cardiomyopathy_3:pathophysiology:Alpha-Tropomyosin%20Thin%20Filament%20Regulatory%20Defect","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Not 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noncompaction remodeling instead of hypertrophy, and the determinants are not established.","intermediate_mechanisms":[],"hypothesis_groups":["tpm1_variant_specific_phenotype_divergence"],"evidence_count":0},{"id":"causal:disorder%3AHypertrophic_Cardiomyopathy_3:0:1","source_id":"node:disorder%3AHypertrophic_Cardiomyopathy_3:pathophysiology:Alpha-Tropomyosin%20Thin%20Filament%20Regulatory%20Defect","target_id":"node:disorder%3AHypertrophic_Cardiomyopathy_3:pathophysiology:Increased%20Myofilament%20Calcium%20Buffering%20and%20Calcium-Dependent%20Signaling","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[1]","label":"Directly 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ventricle","url":"http://purl.obolibrary.org/obo/UBERON_0002084"}],"cell_types":[{"id":"CL:0000746","label":"cardiac muscle cell","display_label":"Cardiomyocyte","url":"http://purl.obolibrary.org/obo/CL_0000746"},{"id":"CL:0002548","label":"fibroblast of cardiac tissue","display_label":"Cardiac Fibroblast","url":"http://purl.obolibrary.org/obo/CL_0002548"}],"biological_processes":[{"id":"GO:0014898","label":"cardiac muscle hypertrophy in response to stress","display_label":"Cardiac muscle hypertrophy in response to stress","url":"http://purl.obolibrary.org/obo/GO_0014898"},{"id":"GO:0045214","label":"sarcomere organization","display_label":"Sarcomere organization","url":"http://purl.obolibrary.org/obo/GO_0045214"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[],"evidence":[],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Hypertrophic_Cardiomyopathy_3","model_node_id":"model:kb/disorders/Hypertrophic_Cardiomyopathy_3.yaml:Alpha-TM180 transgenic mouse (TPM1 Glu180Gly)","focus_node_id":"node:disorder%3AHypertrophic_Cardiomyopathy_3:pathophysiology:Cardiomyocyte%20Hypertrophy%20with%20Myofiber%20Disarray%20and%20Interstitial%20Fibrosis","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_3.html#pathograph","nodes":[{"id":"model:kb/disorders/Hypertrophic_Cardiomyopathy_3.yaml:Alpha-TM180 transgenic mouse (TPM1 Glu180Gly)","kind":"experimental_model","kind_label":"NAM model","label":"Alpha-TM180 transgenic mouse (TPM1 Glu180Gly)","description":"Cardiac-restricted transgenic mouse expressing alpha-tropomyosin carrying the founding CMH3 allele Glu180Gly. The flagship in vivo model of thin-filament HCM and the only model in this entry that reproduces the whole-organ, whole-organism course: early concentric hypertrophy with fibrosis and atrial enlargement, diastolic dysfunction, increased myofilament calcium sensitivity, and death between four and five months.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_3.html#experimental-model-alpha-tm180-transgenic-mouse-tpm1-glu180gly","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_3:pathophysiology:Cardiomyocyte%20Hypertrophy%20with%20Myofiber%20Disarray%20and%20Interstitial%20Fibrosis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Cardiomyocyte Hypertrophy with Myofiber Disarray and Interstitial Fibrosis","description":"Sustained hypercontractility and calcium-dependent hypertrophic signaling remodel the myocardium into the classic hypertrophic pattern: myocyte hypertrophy, loss of the normal parallel myofibre architecture (disarray), and replacement/interstitial fibrosis, producing wall thickening with a small cavity. Histology in TPM1-mutation hearts is indistinguishable from that of other sarcomeric causes, so the node is a faithful specialization of the generic ventricular-remodeling node rather than a TPM1-specific pathology. Human cardiac biopsies carrying TPM1 variants show loss of sarcomeric structure.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_3.html#pathophysiology-cardiomyocyte-hypertrophy-with-myofiber-disarray-and-interstitial-fibrosis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_3:pathophysiology:Arrhythmogenic%20Substrate%20and%20Sudden%20Cardiac%20Death","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Arrhythmogenic Substrate and Sudden Cardiac Death","description":"Myofibre disarray, interstitial and replacement fibrosis, and abnormal calcium handling together create a substrate for reentrant and triggered ventricular arrhythmia. Sudden cardiac death is the outcome that dominates risk stratification in CMH3, and several TPM1 pedigrees have been ascertained through a sudden death. Risk is markedly allele-dependent: sudden-death risk was low in most p.Arg21Leu carriers, whereas other alleles - and digenic thin-plus-thick-filament genotypes - have been associated with severe disease and sudden death.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_3.html#pathophysiology-arrhythmogenic-substrate-and-sudden-cardiac-death","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_3:pathophysiology:Cardiomyocyte%20Hypercontractility%20and%20Impaired%20Relaxation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Cardiomyocyte Hypercontractility and Impaired Relaxation","description":"At the level of the working myocyte the regulatory defect presents as hypercontractility with a relaxation deficit: three-dimensional engineered heart tissues carrying TPM1 HCM variants generate excess force, relax slowly, and show diastolic dysfunction, together with induction of hypertrophic gene markers and cellular hypertrophy. Patient-derived hiPSC-cardiomyocytes carrying the classic Asp175Asn allele reproduce the cellular phenotype with increased cell size and altered calcium handling and electrophysiology. Hypercontractility is the pathophysiological abnormality that myosin-inhibitor therapy is designed to reverse.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_3.html#pathophysiology-cardiomyocyte-hypercontractility-and-impaired-relaxation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_3:pathophysiology:Diastolic%20Dysfunction%20and%20Left%20Ventricular%20Outflow%20Tract%20Obstruction","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Diastolic Dysfunction and Left Ventricular Outflow Tract Obstruction","description":"The stiffened, hypertrophied, fibrotic ventricle fills poorly, and when hypertrophy is asymmetric and septal it can also obstruct the left ventricular outflow tract dynamically. The clinical result is exertional dyspnoea, chest pain, and reduced exercise capacity with preserved or supranormal ejection fraction. Thin-filament HCM as a class tends to produce relatively less hypertrophy and less outflow obstruction than thick-filament HCM while carrying more heart-failure morbidity, so the obstructive presentation should not be assumed in a TPM1 carrier.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_3.html#pathophysiology-diastolic-dysfunction-and-left-ventricular-outflow-tract-obstruction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_3:pathophysiology:Increased%20Myofilament%20Calcium%20Buffering%20and%20Calcium-Dependent%20Signaling","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Increased Myofilament Calcium Buffering and Calcium-Dependent Signaling","description":"Because the mutant thin filament binds calcium more tightly, more of the cytosolic calcium transient is sequestered on the myofilaments. Diastolic calcium rises and reuptake slows; compensatory changes in sodium/calcium exchange, SERCA2 activity, and ryanodine-receptor leak follow, driven by CaMKII phosphorylation. The altered calcium environment chronically engages the calcineurin/NFAT and ERK pathways that transcriptionally program cardiomyocyte hypertrophy, and also creates a substrate for triggered arrhythmia.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_3.html#pathophysiology-increased-myofilament-calcium-buffering-and-calcium-dependent-signaling","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:1:model:kb/disorders/Hypertrophic_Cardiomyopathy_3.yaml:Alpha-TM180 transgenic mouse (TPM1 Glu180Gly)","source_id":"model:kb/disorders/Hypertrophic_Cardiomyopathy_3.yaml:Alpha-TM180 transgenic mouse (TPM1 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cardiac muscle","url":"http://purl.obolibrary.org/obo/GO_0055119"},{"id":"GO:0060047","label":"heart contraction","display_label":"Heart contraction","url":"http://purl.obolibrary.org/obo/GO_0060047"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[],"evidence":[],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Hypertrophic_Cardiomyopathy_3","model_node_id":"model:kb/disorders/Hypertrophic_Cardiomyopathy_3.yaml:Alpha-TM180 transgenic mouse (TPM1 Glu180Gly)","focus_node_id":"node:disorder%3AHypertrophic_Cardiomyopathy_3:pathophysiology:Diastolic%20Dysfunction%20and%20Left%20Ventricular%20Outflow%20Tract%20Obstruction","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_3.html#pathograph","nodes":[{"id":"model:kb/disorders/Hypertrophic_Cardiomyopathy_3.yaml:Alpha-TM180 transgenic mouse (TPM1 Glu180Gly)","kind":"experimental_model","kind_label":"NAM 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The flagship in vivo model of thin-filament HCM and the only model in this entry that reproduces the whole-organ, whole-organism course: early concentric hypertrophy with fibrosis and atrial enlargement, diastolic dysfunction, increased myofilament calcium sensitivity, and death between four and five months.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_3.html#experimental-model-alpha-tm180-transgenic-mouse-tpm1-glu180gly","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_3:pathophysiology:Diastolic%20Dysfunction%20and%20Left%20Ventricular%20Outflow%20Tract%20Obstruction","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Diastolic Dysfunction and Left Ventricular Outflow Tract Obstruction","description":"The stiffened, hypertrophied, fibrotic ventricle fills poorly, and when hypertrophy is asymmetric and septal it can also obstruct the left ventricular outflow tract dynamically. The clinical result is exertional dyspnoea, chest pain, and reduced exercise capacity with preserved or supranormal ejection fraction. Thin-filament HCM as a class tends to produce relatively less hypertrophy and less outflow obstruction than thick-filament HCM while carrying more heart-failure morbidity, so the obstructive presentation should not be assumed in a TPM1 carrier.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_3.html#pathophysiology-diastolic-dysfunction-and-left-ventricular-outflow-tract-obstruction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_3:pathophysiology:Cardiomyocyte%20Hypercontractility%20and%20Impaired%20Relaxation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Cardiomyocyte Hypercontractility and Impaired Relaxation","description":"At the level of the working myocyte the regulatory defect presents as hypercontractility with a relaxation deficit: three-dimensional engineered heart tissues carrying TPM1 HCM variants generate excess force, relax slowly, and show diastolic dysfunction, together with induction of hypertrophic gene markers and cellular hypertrophy. Patient-derived hiPSC-cardiomyocytes carrying the classic Asp175Asn allele reproduce the cellular phenotype with increased cell size and altered calcium handling and electrophysiology. Hypercontractility is the pathophysiological abnormality that myosin-inhibitor therapy is designed to reverse.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_3.html#pathophysiology-cardiomyocyte-hypercontractility-and-impaired-relaxation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_3:pathophysiology:Cardiomyocyte%20Hypertrophy%20with%20Myofiber%20Disarray%20and%20Interstitial%20Fibrosis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Cardiomyocyte Hypertrophy with Myofiber Disarray and Interstitial Fibrosis","description":"Sustained hypercontractility and calcium-dependent hypertrophic signaling remodel the myocardium into the classic hypertrophic pattern: myocyte hypertrophy, loss of the normal parallel myofibre architecture (disarray), and replacement/interstitial fibrosis, producing wall thickening with a small cavity. Histology in TPM1-mutation hearts is indistinguishable from that of other sarcomeric causes, so the node is a faithful specialization of the generic ventricular-remodeling node rather than a TPM1-specific pathology. Human cardiac biopsies carrying TPM1 variants show loss of sarcomeric structure.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_3.html#pathophysiology-cardiomyocyte-hypertrophy-with-myofiber-disarray-and-interstitial-fibrosis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_3:pathophysiology:Progressive%20Heart%20Failure","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Progressive Heart Failure","description":"A minority of CMH3 patients progress to symptomatic heart failure, and thin-filament HCM as a class carries higher heart-failure morbidity than thick-filament HCM. Outcome nonetheless remains strongly allele-dependent: survival free of cardiovascular death or transplant was 87.5% at 50 years in the p.Arg21Leu founder series, and near-normal life expectancy was reported for Asp175Asn.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_3.html#pathophysiology-progressive-heart-failure","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:2:model:kb/disorders/Hypertrophic_Cardiomyopathy_3.yaml:Alpha-TM180 transgenic mouse (TPM1 Glu180Gly)","source_id":"model:kb/disorders/Hypertrophic_Cardiomyopathy_3.yaml:Alpha-TM180 transgenic mouse (TPM1 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Hypertrophy with Myofiber Disarray and Interstitial Fibrosis","Diastolic Dysfunction and Left Ventricular Outflow Tract Obstruction"],"relationships":["Not Specified"],"fidelities":["Not Specified"],"biological_scales":["Molecular","Tissue","Organism"],"system_context_sources":["Model-level cell type","Linked mechanism anatomy","Linked mechanism cell type","Linked mechanism biological scale"],"modeled_system_labels":["myocardium","interventricular septum","heart left ventricle","cardiac muscle cell","fibroblast of cardiac tissue","Molecular","Tissue","Organism"],"biological_process_terms":[{"id":"GO:0006937","label":"regulation of muscle contraction","display_label":"Regulation of muscle contraction","url":"http://purl.obolibrary.org/obo/GO_0006937"},{"id":"GO:0014898","label":"cardiac muscle hypertrophy in response to stress","display_label":"Cardiac muscle hypertrophy in response to stress","url":"http://purl.obolibrary.org/obo/GO_0014898"},{"id":"GO:0045214","label":"sarcomere organization","display_label":"Sarcomere organization","url":"http://purl.obolibrary.org/obo/GO_0045214"},{"id":"GO:0055119","label":"relaxation of cardiac muscle","display_label":"Relaxation of cardiac muscle","url":"http://purl.obolibrary.org/obo/GO_0055119"},{"id":"GO:0060047","label":"heart contraction","display_label":"Heart contraction","url":"http://purl.obolibrary.org/obo/GO_0060047"}],"biological_processes":["regulation of muscle contraction","cardiac muscle hypertrophy in response to stress","sarcomere organization","relaxation of cardiac muscle","heart contraction"],"pathway_terms":[],"pathways":[],"gene_terms":[{"id":"hgnc:12010","label":"TPM1","display_label":"TPM1","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/12010"}],"genes":["TPM1"],"chemical_terms":[],"chemicals":[],"readout_names":[],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[{"statement":"Ventricular concentric hypertrophy, fibrosis, and atrial enlargement within one month; progressive worsening with death between four and five months; diastolic dysfunction and increased myofilament calcium sensitivity.","evidence":[]}],"findings_text":["Ventricular concentric hypertrophy, fibrosis, and atrial enlargement within one month; progressive worsening with death between four and five months; diastolic dysfunction and increased myofilament calcium sensitivity."],"evidence":[{"reference":"PMID:11603924","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/11603924","reference_title":"A familial hypertrophic cardiomyopathy alpha-tropomyosin mutation causes severe cardiac hypertrophy and death in mice.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"This study developed transgenic mouse lines that encode an FHC mutation in alpha-tropomyosin","explanation":"Describes construction of the model."},{"reference":"PMID:11603924","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/11603924","reference_title":"A familial hypertrophic cardiomyopathy alpha-tropomyosin mutation causes severe cardiac hypertrophy and death in mice.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"The disease-associated changes progressively increase and result in death between 4 and 5 months.","explanation":"Gives the model's natural history and endpoint."}],"evidence_text":["This study developed transgenic mouse lines that encode an FHC mutation in alpha-tropomyosin","The disease-associated changes progressively increase and result in death between 4 and 5 months.","Describes construction of the model.","Gives the model's natural history and endpoint."],"evidence_status":"Evidence recorded","metadata_completeness":70,"metadata_present":["Model category","Organism","Anatomy","Cell type","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Cell source","Culture system"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Hypertrophic_Cardiomyopathy_3.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hypertrophic_Cardiomyopathy_3.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_3.html#experimental-model-alpha-tm180-transgenic-mouse-tpm1-glu180gly","source_anchor":"experimental-model-alpha-tm180-transgenic-mouse-tpm1-glu180gly"},{"id":"model:kb/disorders/Platelet-type_Bleeding_Disorder_16.yaml:alphaIIb-W995/beta3-transduced mouse fetal liver-derived megakaryocytes","name":"alphaIIb-W995/beta3-transduced mouse fetal liver-derived megakaryocytes","description":"Megakaryocytes differentiated from mouse fetal liver cells after transduction with the human alphaIIb R995W allele together with beta3. This is the model that connects the receptor lesion to the platelet count: it puts the patient's allele into a cell that actually makes platelets, and asks what the proplatelets look like.\n","notes":null,"context_id":"disorder:Platelet-type_Bleeding_Disorder_16","context_kind":"Disorder","disease_name":"Platelet-type Bleeding Disorder 16","disease_synonyms":["BDPLT16","bleeding disorder, platelet-type, 16","bleeding disorder, platelet-type, 16, autosomal dominant","autosomal dominant Glanzmann thrombasthenia","Glanzmann thrombasthenia, autosomal dominant","thrombasthenia of Glanzmann and Naegeli, autosomal dominant","autosomal dominant thrombasthenia of Glanzmann and Naegeli","Glanzmann thrombasthenia-like syndrome","ITGA2B-related macrothrombocytopenia","ITGA2B/ITGB3-related thrombocytopenia"],"disease_term":{"id":"MONDO:0008552","label":"platelet-type bleeding disorder 16","display_label":"platelet-type bleeding disorder 16","url":"http://purl.obolibrary.org/obo/MONDO_0008552"},"experimental_model_type":"PRIMARY_CELL_CULTURE","experimental_model_type_label":"Primary-cell culture","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"},"organism_label":"Mus musculus","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[{"id":"CL:0000556","label":"megakaryocyte","display_label":"megakaryocyte","url":"http://purl.obolibrary.org/obo/CL_0000556"}],"model_cell_type_labels":["megakaryocyte"],"linked_cell_types":[{"id":"CL:0000556","label":"megakaryocyte","display_label":"megakaryocyte","url":"http://purl.obolibrary.org/obo/CL_0000556"}],"linked_cell_type_labels":["megakaryocyte"],"cell_types":[{"id":"CL:0000556","label":"megakaryocyte","display_label":"megakaryocyte","url":"http://purl.obolibrary.org/obo/CL_0000556"}],"cell_type_labels":["megakaryocyte"],"conditions":[],"cell_source":"Mouse fetal liver haematopoietic cells, retrovirally transduced","source_category":"Primary / biopsy-derived","culture_system":null,"publication":"PMID:21454453","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/21454453","mechanisms":[{"target":"Abnormal Proplatelet Formation by Megakaryocytes","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Platelet-type_Bleeding_Disorder_16.html#pathophysiology-abnormal-proplatelet-formation-by-megakaryocytes","relationship":"RECAPITULATES","relationship_label":"Recapitulates","fidelity":"MODERATE","fidelity_label":"Moderate","description":"Transduced megakaryocytes form proplatelets with fewer and larger tips, which is the cellular defect this node asserts.","limitations":"The human allele is expressed in a mouse megakaryocyte alongside the endogenous mouse integrin and at a transduced rather than heterozygous level, so the gene dosage is not the patient's. Proplatelet tips in culture are a surrogate for platelet release in the marrow, and no platelet count or bleeding phenotype is measured.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[{"id":"CL:0000556","label":"megakaryocyte","display_label":"megakaryocyte","url":"http://purl.obolibrary.org/obo/CL_0000556"}],"biological_processes":[{"id":"GO:0030220","label":"platelet formation","display_label":"platelet formation","url":"http://purl.obolibrary.org/obo/GO_0030220"},{"id":"GO:0030036","label":"actin cytoskeleton organization","display_label":"actin cytoskeleton organization","url":"http://purl.obolibrary.org/obo/GO_0030036"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Proplatelet tip number and size","description":null,"target":"Abnormal Proplatelet Formation by Megakaryocytes","direction":"ALTERED","interpretation":"Fewer tips of larger size is the culture correlate of releasing fewer and larger platelets.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:21454453","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/21454453","reference_title":"Heterozygous ITGA2B R995W mutation inducing constitutive activation of the αIIbβ3 receptor affects proplatelet formation and causes congenital macrothrombocytopenia.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The increased size and decreased number of proplatelet tips in αIIb-W995/β3-transduced mouse fetal liver-derived megakaryocytes indicate defective pro-platelet formation.","explanation":"The measurement and the authors' reading of it."}],"notes":null}],"evidence":[{"reference":"PMID:21454453","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/21454453","reference_title":"Heterozygous ITGA2B R995W mutation inducing constitutive activation of the αIIbβ3 receptor affects proplatelet formation and causes congenital macrothrombocytopenia.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"We propose that activating mutations in ITGA2B and ITGB3 represent the etiology of a subset of congenital macrothrombocytopenias.","explanation":"The inference this model licenses, and the reason it is treated as informative for the production defect."},{"reference":"PMID:21454453","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/21454453","reference_title":"Heterozygous ITGA2B R995W mutation inducing constitutive activation of the αIIbβ3 receptor affects proplatelet formation and causes congenital macrothrombocytopenia.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The increased size and decreased number of proplatelet tips in αIIb-W995/β3-transduced mouse fetal liver-derived megakaryocytes indicate defective pro-platelet formation.","explanation":"The measurement and the authors' reading of it."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Platelet-type_Bleeding_Disorder_16","model_node_id":"model:kb/disorders/Platelet-type_Bleeding_Disorder_16.yaml:alphaIIb-W995/beta3-transduced mouse fetal liver-derived megakaryocytes","focus_node_id":"node:disorder%3APlatelet-type_Bleeding_Disorder_16:pathophysiology:Abnormal%20Proplatelet%20Formation%20by%20Megakaryocytes","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Platelet-type_Bleeding_Disorder_16.html#pathograph","nodes":[{"id":"model:kb/disorders/Platelet-type_Bleeding_Disorder_16.yaml:alphaIIb-W995/beta3-transduced mouse fetal liver-derived megakaryocytes","kind":"experimental_model","kind_label":"NAM model","label":"alphaIIb-W995/beta3-transduced mouse fetal liver-derived megakaryocytes","description":"Megakaryocytes differentiated from mouse fetal liver cells after transduction with the human alphaIIb R995W allele together with beta3. 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This is the quantitative arm of the disorder, which the primary_hemostatic_plug_failure module deliberately does not model, so no node here conforms to it.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Platelet-type_Bleeding_Disorder_16.html#pathophysiology-abnormal-proplatelet-formation-by-megakaryocytes","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APlatelet-type_Bleeding_Disorder_16:phenotype:Abnormal%20Platelet%20Alpha-Granules","kind":"phenotype","kind_label":"Phenotype","label":"Abnormal Platelet Alpha-Granules","description":"Enlarged alpha-granules, some giant and showing signs of fusion, on electron microscopy of large round platelets. 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Plasma thrombopoietin is normal, and in one patient the count rose transiently after an influenza infection, both arguing against a profound global failure of thrombopoiesis.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Platelet-type_Bleeding_Disorder_16.html#pathophysiology-reduced-output-of-enlarged-circulating-platelets","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Platelet-type_Bleeding_Disorder_16.yaml:alphaIIb-W995/beta3-transduced mouse fetal liver-derived megakaryocytes","source_id":"model:kb/disorders/Platelet-type_Bleeding_Disorder_16.yaml:alphaIIb-W995/beta3-transduced mouse fetal liver-derived 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When the cotransfection of the two plasmids was conducted, the concentration of each plasmid is 1.5 μg/ml.","explanation":"Dose difference limits a clean interaction interpretation."}],"evidence_text":["The cells lysates were used to analyze the AR protein expression by Western blot.","The transfection concentration of a single plasmid was 2.5 μg/ml. 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androgen-elicited growth inhibition of KCs in a dose-dependent manner.","The growth effect occurs in the receptor-transfected preparation.","Androgen increased secreted TGF-beta1 in AR-transfected dermal papilla culture.","Neutralization supports a TGF-beta1-dependent component."],"evidence_status":"Evidence recorded","metadata_completeness":60,"metadata_present":["Model category","NAMO class","Cell type","Cell source","Modeled mechanism","Evidence"],"metadata_missing":["Organism","Anatomy","Culture system","Publication"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Androgenetic_Alopecia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Androgenetic_Alopecia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Androgenetic_Alopecia.html#experimental-model-ar-transfected-human-dermal-papilla-and-keratinocyte-coculture","source_anchor":"experimental-model-ar-transfected-human-dermal-papilla-and-keratinocyte-coculture"},{"id":"model:kb/disorders/BEST1_Bestrophinopathies.yaml:ARB p.Arg141His/p.Ile366fsTer18 family iPSC-RPE model","name":"ARB p.Arg141His/p.Ile366fsTer18 family iPSC-RPE model","description":"Multiple clones from one affected donor, her heterozygous parents and three unrelated controls were studied using RNA assays, immunoblotting, localization and outer-segment uptake assays. 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The causal contribution of reduced BEST1 abundance versus mutant-protein dysfunction was unresolved.","url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathophysiology-impaired-photoreceptor-outer-segment-internalization","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:BEST1%20Channel%20Dysfunction","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"BEST1 Channel Dysfunction","description":"BEST1 encodes a pentameric calcium-activated anion channel of the RPE basolateral membrane. 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The allelic disorder HSN1D shows that ATL1 variants can injure long peripheral axons on their own.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hereditary_Spastic_Paraplegia_3A.html#pathophysiology-distal-axonal-degeneration-of-peripheral-motor-and-sensory-nerves","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHereditary_Spastic_Paraplegia_3A:pathophysiology:Disrupted%20Tubular%20ER%20Network%20in%20Neurons","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Disrupted Tubular ER Network in Neurons","description":"Without atlastin-1-mediated fusion the peripheral ER of the neuron becomes long, unbranched and poorly interconnected: three-way junctions are lost, the network retracts from distal neurites, and ER-microtubule coordination through the atlastin-1, spastin and REEP1 complex is disturbed. In the corticospinal axons of the Atl1 K80A knock-in, Reep1-null mouse the axonal ER instead expands transversely into a periodic ladder-like structure, dosage-dependently, with fragmented mitochondria and hypophosphorylated neurofilaments in lockstep. Whether the ER of patient corticospinal axons shows either change is not known.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hereditary_Spastic_Paraplegia_3A.html#pathophysiology-disrupted-tubular-er-network-in-neurons","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHereditary_Spastic_Paraplegia_3A:phenotype:Distal%20amyotrophy","kind":"phenotype","kind_label":"Phenotype","label":"Distal amyotrophy","description":"Lower motor neuron involvement in the complicated (Silver syndrome) phenotype produces distal muscle wasting, most often in the lower limbs; wasting in the lower limbs is more frequent in SPG3A than in SPG4.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hereditary_Spastic_Paraplegia_3A.html#phenotype-distal-amyotrophy","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHereditary_Spastic_Paraplegia_3A:pathophysiology:Impaired%20Axonal%20ER%20Distribution%2C%20Organelle%20Transport%20and%20Axon%20Growth","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Axonal ER Distribution, Organelle Transport and Axon Growth","description":"Atlastin-1 is enriched in growth cones, axonal varicosities and branch points of cortical neurons, and its knockdown or mutation reduces axon formation and elongation. 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Every other model here is either a mouse or a patient: the mouse matches the dosage but not the species, and the patients match the species but cannot separate the BACH2 lesion from everything else in their genomes and histories. Knocking BACH2 down by about half in healthy donor cells does both at once - human cells, human gene dosage, one variable changed - and it reproduces the patients' phenotype in both lineages: PRDM1 rises, CD4+ T cells proliferate less, and class switching to IgG and IgA is suppressed.","url":"https://dismech.monarchinitiative.org/pages/disorders/Immunodeficiency_60.html#experimental-model-bach2-rnai-knockdown-in-primary-human-t-and-b-cells","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AImmunodeficiency_60:pathophysiology:BACH2%20Haploinsufficiency","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"BACH2 Haploinsufficiency","description":"Loss of one functional BACH2 allele leaves insufficient BACH2 protein to specify lymphocyte lineage decisions. IUIS characterises the defect as haploinsufficiency for a critical lineage specification transcription factor, which is a dosage statement rather than a dominant-negative one: the residual wild-type allele is not poisoned, it is simply not enough. BACH2 is required in both lymphoid lineages, which is why one dosage lesion produces a T-cell and a B-cell defect at once.","url":"https://dismech.monarchinitiative.org/pages/disorders/Immunodeficiency_60.html#pathophysiology-bach2-haploinsufficiency","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AImmunodeficiency_60:pathophysiology:BACH2%20Protein%20Destabilization","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"BACH2 Protein Destabilization","description":"The step that explains why one mutant allele yields half-dosage rather than a poisoned pathway. The reported BRIDA mutations do not produce a dominant-negative protein; they destabilize BACH2 itself, either by interfering with homodimerization through the BTB/POZ domain or by driving the protein into aggregates. The mutant product is therefore lost rather than interfering, which is what makes the downstream defect a pure gene-dosage problem.","url":"https://dismech.monarchinitiative.org/pages/disorders/Immunodeficiency_60.html#pathophysiology-bach2-protein-destabilization","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AImmunodeficiency_60:pathophysiology:Gut-Homing%20Receptor%20Upregulation%20on%20CD4%2B%20T%20Cells","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Gut-Homing Receptor Upregulation on CD4+ T Cells","description":"The addressing half, and what makes the tissue infiltration land in the gut. A Treg deficit on its own predicts autoimmunity without predicting where it will appear; in BRIDA the CD4+ compartment carries raised levels of the two receptors that direct a T cell to intestinal tissue, CCR9 and beta-7 integrin. The same shift is reproduced at matched gene dosage in the heterozygous mouse, which is what makes it a consequence of halving BACH2 rather than a reaction to established colitis.","url":"https://dismech.monarchinitiative.org/pages/disorders/Immunodeficiency_60.html#pathophysiology-gut-homing-receptor-upregulation-on-cd4-t-cells","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AImmunodeficiency_60:pathophysiology:Impaired%20Memory%20B%20Cell%20Development","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Memory B Cell Development","description":"The B-cell arm of the defect. IUIS records impaired memory B-cell development as the circulating B-cell finding in BACH2 deficiency. Mechanistically BACH2 sits upstream of the memory-versus-plasma-cell decision: in normal human memory B cells, differentiation to plasma cells is driven by PRDM1/BLIMP1 induction with reciprocal downregulation of BACH2, so BACH2 is the repressor that holds the memory programme open. Insufficient BACH2 leaves that programme unable to be established, and the memory B-cell compartment that supplies durable mucosal and respiratory antibody does not accumulate.\nThe founding report's full text resolves how far the defect goes, which earlier versions of this entry left open. The loss in patients is not only of memory B cells but specifically of class-switched ones, and activating patient naive B cells in vitro reproduces the failure directly: class-switch recombination, plasmablast generation and class-switched antibody secretion are all impaired. Isotype switching is therefore annotated here as a patient-level defect rather than a mouse inference.","url":"https://dismech.monarchinitiative.org/pages/disorders/Immunodeficiency_60.html#pathophysiology-impaired-memory-b-cell-development","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AImmunodeficiency_60:pathophysiology:Impaired%20Regulatory%20T%20Cell%20Differentiation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Regulatory T Cell Differentiation","description":"BACH2 is one of the transcription factors whose loss defines the monogenic \"Tregopathies\" - inborn errors of immunity that act through the regulatory T-cell compartment rather than through effector immunity. Insufficient BACH2 impairs regulatory T-cell differentiation, and the resulting failure of peripheral tolerance is the arm of the disease that produces lymphocytic tissue infiltration rather than infection.","url":"https://dismech.monarchinitiative.org/pages/disorders/Immunodeficiency_60.html#pathophysiology-impaired-regulatory-t-cell-differentiation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AImmunodeficiency_60:phenotype:Progressive%20T-cell%20lymphopenia","kind":"phenotype","kind_label":"Phenotype","label":"Progressive T-cell lymphopenia","description":"IUIS records the circulating T-cell finding in BACH2 deficiency as progressive T-cell lymphopenia. The qualifier matters: the count falls over time rather than being low from the outset, so a normal T-cell count early does not exclude the diagnosis.","url":"https://dismech.monarchinitiative.org/pages/disorders/Immunodeficiency_60.html#phenotype-progressive-t-cell-lymphopenia","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AImmunodeficiency_60:pathophysiology:TH1%20Effector%20Skewing","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"TH1 Effector Skewing","description":"The effector half of the T-cell lesion. Insufficient BACH2 releases the repression that normally restrains effector lineage commitment, and the patients' CD4+ compartment is pushed towards the TH1 programme, marked by raised T-bet. This says what the surviving cells become; where they go is the separate node below.","url":"https://dismech.monarchinitiative.org/pages/disorders/Immunodeficiency_60.html#pathophysiology-th1-effector-skewing","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Immunodeficiency_60.yaml:BACH2 RNAi knockdown in primary human T and B cells","source_id":"model:kb/disorders/Immunodeficiency_60.yaml:BACH2 RNAi knockdown in primary human T and B 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Healthy donor cells, so it says what BACH2 dosage does and not what the specific BRIDA alleles do.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[{"id":"CL:0000787","label":"memory B cell","display_label":"memory B cell","url":"http://purl.obolibrary.org/obo/CL_0000787"},{"id":"CL:0000979","label":"IgG memory B cell","display_label":"IgG class-switched memory B cell","url":"http://purl.obolibrary.org/obo/CL_0000979"}],"biological_processes":[{"id":"GO:0002319","label":"memory B cell differentiation","display_label":"memory B cell differentiation","url":"http://purl.obolibrary.org/obo/GO_0002319"},{"id":"GO:0045190","label":"isotype switching","display_label":"immunoglobulin class switch recombination","url":"http://purl.obolibrary.org/obo/GO_0045190"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"In vitro class switch recombination to IgG and IgA after BACH2 knockdown","description":null,"target":"Impaired Memory B Cell Development","direction":"DECREASED","interpretation":"The isotype-switching step of this node, shown to depend on BACH2 dosage in human cells.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:28530713","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/28530713","reference_title":"BACH2 immunodeficiency illustrates an association between super-enhancers and haploinsufficiency.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"silencing BACH2 in healthy control B cells, significantly suppressed in vitro class switch recombination towards the IgG and IgA isotypes","explanation":"Reports the measurement behind this readout."}],"notes":null}],"evidence":[{"reference":"PMID:28530713","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/28530713","reference_title":"BACH2 immunodeficiency illustrates an association between super-enhancers and haploinsufficiency.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"silencing BACH2 in healthy control B cells, significantly suppressed in vitro class switch recombination towards the IgG and IgA isotypes","explanation":"Supports treating the knockdown as informative for the class-switch arm of this node, in human cells at approximately the human heterozygous dosage."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Immunodeficiency_60","model_node_id":"model:kb/disorders/Immunodeficiency_60.yaml:BACH2 RNAi knockdown in primary human T and B cells","focus_node_id":"node:disorder%3AImmunodeficiency_60:pathophysiology:Impaired%20Memory%20B%20Cell%20Development","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Immunodeficiency_60.html#pathograph","nodes":[{"id":"model:kb/disorders/Immunodeficiency_60.yaml:BACH2 RNAi knockdown in primary human T and B cells","kind":"experimental_model","kind_label":"NAM model","label":"BACH2 RNAi knockdown in primary human T and B cells","description":"The dose-matched human system, and the strongest causal evidence in this entry. 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IUIS records impaired memory B-cell development as the circulating B-cell finding in BACH2 deficiency. Mechanistically BACH2 sits upstream of the memory-versus-plasma-cell decision: in normal human memory B cells, differentiation to plasma cells is driven by PRDM1/BLIMP1 induction with reciprocal downregulation of BACH2, so BACH2 is the repressor that holds the memory programme open. Insufficient BACH2 leaves that programme unable to be established, and the memory B-cell compartment that supplies durable mucosal and respiratory antibody does not accumulate.\nThe founding report's full text resolves how far the defect goes, which earlier versions of this entry left open. The loss in patients is not only of memory B cells but specifically of class-switched ones, and activating patient naive B cells in vitro reproduces the failure directly: class-switch recombination, plasmablast generation and class-switched antibody secretion are all impaired. Isotype switching is therefore annotated here as a patient-level defect rather than a mouse inference.","url":"https://dismech.monarchinitiative.org/pages/disorders/Immunodeficiency_60.html#pathophysiology-impaired-memory-b-cell-development","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AImmunodeficiency_60:pathophysiology:BACH2%20Haploinsufficiency","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"BACH2 Haploinsufficiency","description":"Loss of one functional BACH2 allele leaves insufficient BACH2 protein to specify lymphocyte lineage decisions. 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Both founding families and the later R576L family show it, including in the two individuals whose other isotypes are normal or raised, which makes IgA the most consistent single humoral marker in this disorder and the reason a normal total IgG should not close the question.","url":"https://dismech.monarchinitiative.org/pages/disorders/Immunodeficiency_60.html#phenotype-decreased-circulating-iga-concentration","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AImmunodeficiency_60:phenotype:Decreased%20class-switched%20memory%20B%20cell%20proportion","kind":"phenotype","kind_label":"Phenotype","label":"Decreased class-switched memory B cell proportion","description":"The switched subset is depleted specifically, not merely in proportion to the memory compartment as a whole. That is the finding that points at class-switch recombination rather than at memory formation in general, and it is curated separately from the memory B-cell phenotype for that reason.","url":"https://dismech.monarchinitiative.org/pages/disorders/Immunodeficiency_60.html#phenotype-decreased-class-switched-memory-b-cell-proportion","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AImmunodeficiency_60:phenotype:Decreased%20memory%20B%20cell%20proportion","kind":"phenotype","kind_label":"Phenotype","label":"Decreased memory B cell proportion","description":"Reduction of the CD27+ memory B-cell compartment, measured directly in the founding patients. It is the cellular counterpart of the antibody deficiency and, in the second reported family, was present in a clinically unaffected carrier - so it may be the earliest detectable sign in a relative.","url":"https://dismech.monarchinitiative.org/pages/disorders/Immunodeficiency_60.html#phenotype-decreased-memory-b-cell-proportion","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AImmunodeficiency_60:phenotype:Decreased%20specific%20antibody%20response%20to%20vaccination","kind":"phenotype","kind_label":"Phenotype","label":"Decreased specific antibody response to vaccination","description":"Failure to mount protective antibody after immunization, reported in all three founding subjects. It is the functional test that converts a low immunoglobulin concentration into a demonstrated antibody deficiency, and it is what the authors rest their common-variable-immunodeficiency characterisation on.","url":"https://dismech.monarchinitiative.org/pages/disorders/Immunodeficiency_60.html#phenotype-decreased-specific-antibody-response-to-vaccination","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AImmunodeficiency_60:phenotype:Immunoglobulin%20deficiency","kind":"phenotype","kind_label":"Phenotype","label":"Immunoglobulin deficiency","description":"The humoral consequence of the failed B-cell maturation programme, and the finding that makes the disorder look like a predominantly antibody deficiency at the bedside.\nWhich isotypes fall is now curated from the founding report's full text, and the answer is that it varies between patients rather than tracking the variant. Two of the three founding subjects - the L24P proband and the E788K father - were low in IgM, IgG, IgA and IgE together. The third, the father's daughter and so a carrier of the same E788K allele, had low IgA against raised IgM and raised IgG. IgA is the only isotype low in all three. A later, unrelated family carrying R576L again showed IgA deficiency. So a normal or high IgG does not exclude the diagnosis, and the humoral phenotype should be read per isotype rather than as a single grade.\nWhat is still not curated is how far each isotype falls. The concentrations are reported in a supplementary table that is not part of the retrievable article, so this entry records direction and not values, and carries no reference ranges.","url":"https://dismech.monarchinitiative.org/pages/disorders/Immunodeficiency_60.html#phenotype-immunoglobulin-deficiency","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:1:model:kb/disorders/Immunodeficiency_60.yaml:BACH2 RNAi knockdown in primary human T and B cells","source_id":"model:kb/disorders/Immunodeficiency_60.yaml:BACH2 RNAi knockdown in primary human T and B 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after BACH2 knockdown"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:28530713","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/28530713","reference_title":"BACH2 immunodeficiency illustrates an association between super-enhancers and haploinsufficiency.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"we silenced BACH2 expression in healthy control T and B cells using RNAi by ~50% and carried out functional phenotyping","explanation":"States the system and the knockdown depth, which is what makes it dose-matched to a heterozygous human and therefore informative for this node."},{"reference":"PMID:28530713","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/28530713","reference_title":"BACH2 immunodeficiency illustrates an association between super-enhancers and 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entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Immunodeficiency_60.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Immunodeficiency_60.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Immunodeficiency_60.html#experimental-model-bach2-rnai-knockdown-in-primary-human-t-and-b-cells","source_anchor":"experimental-model-bach2-rnai-knockdown-in-primary-human-t-and-b-cells"},{"id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_13.yaml:Baculovirus complementation of patient fibroblasts","name":"Baculovirus complementation of patient fibroblasts","description":"The rescue experiment from the founding study. Patient fibroblasts carrying the homozygous splice allele were transduced with a baculovirus expressing wild-type NDUFA2, and complex I expression, complex I activity and the mitochondrial membrane potential all improved. The rescue is described as partial, which the entry keeps - complementation establishes causality without establishing that the defect is fully correctable.","notes":null,"context_id":"disorder:Mitochondrial_Complex_I_Deficiency_Nuclear_Type_13","context_kind":"Disorder","disease_name":"Mitochondrial Complex I Deficiency, Nuclear Type 13","disease_synonyms":["MC1DN13","NDUFA2-related mitochondrial complex I deficiency","NDUFA2 deficiency"],"disease_term":{"id":"MONDO:0032618","label":"mitochondrial complex I deficiency, nuclear type 13","display_label":"Mitochondrial complex I deficiency, nuclear type 13","url":"http://purl.obolibrary.org/obo/MONDO_0032618"},"experimental_model_type":"PRIMARY_CELL_CULTURE","experimental_model_type_label":"Primary-cell culture","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":null,"source_category":"Primary / biopsy-derived","culture_system":null,"publication":null,"publication_url":null,"mechanisms":[{"target":"Isolated Complex I Deficiency","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_13.html#pathophysiology-isolated-complex-i-deficiency","relationship":"RESCUES","relationship_label":"Rescues","fidelity":"HIGH","fidelity_label":"High","description":"Supplying wild-type NDUFA2 to the patient's own cells restores what the variant took away, which is the standard demonstration that a candidate variant is causal.","limitations":"The rescue is partial rather than complete, and the reason is not resolved - transduction efficiency, expression level and the possibility of an irreversible component are all consistent with the result. The system is a patient fibroblast, so it says nothing about brain or heart, and only the null allele has been tested; the three missense patients have had no complementation experiment. Baculovirus-driven expression is also non-physiological in level and timing.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0006120","label":"mitochondrial electron transport, NADH to ubiquinone","display_label":"mitochondrial electron transport, NADH to ubiquinone","url":"http://purl.obolibrary.org/obo/GO_0006120"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Complex I expression, complex I activity and mitochondrial membrane potential","description":null,"target":"Isolated Complex I Deficiency","direction":"RESTORED","interpretation":"All three measures improve when wild-type NDUFA2 is supplied, and the source qualifies the restoration as partial.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:18513682","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/18513682","reference_title":"NDUFA2 complex I mutation leads to Leigh disease.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The expression and activity of complex I and the depolarization was (partially) rescued with a baculovirus system expressing the NDUFA2 gene.","explanation":"The three readouts and the qualifier the authors put on them."}],"notes":null}],"evidence":[{"reference":"PMID:18513682","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/18513682","reference_title":"NDUFA2 complex I mutation leads to Leigh disease.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"The mutation in this accessory subunit causes reduced activity and disturbed assembly of complex I.","explanation":"The defect the rescue reverses, which is what makes this model informative for the node. Graded HUMAN_CLINICAL rather than IN_VITRO because the sentence attributes the activity and assembly deficit to the patient's mutation and the deficiency was demonstrated in muscle as well as in cultured fibroblasts; the rescue experiment itself, quoted on the readout, is the in-vitro half."},{"reference":"PMID:18513682","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/18513682","reference_title":"NDUFA2 complex I mutation leads to Leigh disease.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The expression and activity of complex I and the depolarization was (partially) rescued with a baculovirus system expressing the NDUFA2 gene.","explanation":"The three readouts and the qualifier the authors put on them."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Mitochondrial_Complex_I_Deficiency_Nuclear_Type_13","model_node_id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_13.yaml:Baculovirus complementation of patient fibroblasts","focus_node_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_13:pathophysiology:Isolated%20Complex%20I%20Deficiency","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_13.html#pathograph","nodes":[{"id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_13.yaml:Baculovirus complementation of patient fibroblasts","kind":"experimental_model","kind_label":"NAM model","label":"Baculovirus complementation of patient fibroblasts","description":"The rescue experiment from the founding study. 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The rescue is described as partial, which the entry keeps - complementation establishes causality without establishing that the defect is fully correctable.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_13.html#experimental-model-baculovirus-complementation-of-patient-fibroblasts","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_13:pathophysiology:Isolated%20Complex%20I%20Deficiency","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Isolated Complex I Deficiency","description":"The measured biochemical endpoint, and the phenotype the entity is named for. The founding patient's deficiency was expressed in both skin fibroblasts and muscle, and it was isolated - the other respiratory chain complexes were spared, which is what a subunit dedicated to complex I predicts and what distinguishes this from the combined deficiencies caused by defects of mitochondrial gene expression. Transducing the patient's cells with a baculovirus expressing wild-type NDUFA2 partially restored complex I expression and activity, which is the experiment that makes the gene causal rather than merely associated.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_13.html#pathophysiology-isolated-complex-i-deficiency","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_13:phenotype:Decreased%20Activity%20of%20Mitochondrial%20Complex%20I","kind":"phenotype","kind_label":"Phenotype","label":"Decreased Activity of Mitochondrial Complex I","description":"The defining biochemical finding, demonstrated in fibroblasts and in muscle in the founding patient and in the two leukoencephalopathy patients. 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GBP1 expression is not specific to BARD1 loss."}],"evidence_text":["We demonstrate that PSaRC318 cells, a novel patient-derived cell line harboring a pathogenic BARD1 variant, are sensitive to PARP inhibition and by testing the effect of BARD1 depletion in additional Ewing sarcoma cell lines, we confirm that BARD1 loss enhances cell sensitivity to PARP inhibition plus radiation.","Here, we demonstrate that GBP1 contributes to the enhanced sensitivity of BARD1 deficient Ewing cells to DNA damage.","Patient-derived and BARD1-depleted cell models support an experimental modifier, not a validated patient biomarker or a ten-percent BARD1 frequency.","GBP1 knockdown reduced radiation- and niraparib-associated apoptosis in PSaRC318 cells; GBP1 expression is not specific to BARD1 loss."],"evidence_status":"Evidence recorded","metadata_completeness":80,"metadata_present":["Model category","NAMO class","Organism","Cell source","Culture system","Modeled mechanism","Publication","Evidence"],"metadata_missing":["Anatomy","Cell type"],"dataset_context":"Available in same entry","context_dataset_ids":["dataset:dbgap:phs000804","dataset:dbgap:phs001549","dataset:ega:egas00001000839","dataset:ega:egas00001000855","dataset:ega:egas00001002161","dataset:massive:msv000082954"],"candidate_dataset_ids":[],"source_path":"kb/disorders/Ewing_Sarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ewing_Sarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#experimental-model-bard1-variant-psarc318-and-bard1-depleted-ewing-cells","source_anchor":"experimental-model-bard1-variant-psarc318-and-bard1-depleted-ewing-cells"},{"id":"model:kb/disorders/Primary_Ciliary_Dyskinesia.yaml:BCi-NS1.1 dyskinetic airway epithelial cell line","name":"BCi-NS1.1 dyskinetic airway epithelial cell line","description":"The reported BCi-NS1.1 culture had slow circular ciliary beating and a central-microtubule defect confirmed by electron microscopy. 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This beat-dysfunction route is distinct from reduced multiciliogenesis and transport failure despite apparently normal routine beat measurements.","url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Ciliary_Dyskinesia.html#pathophysiology-ciliary-dysfunction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APrimary_Ciliary_Dyskinesia:pathophysiology:CCDC39-CCDC40%20Axonemal%20Scaffold%20Loss","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"CCDC39-CCDC40 Axonemal Scaffold Loss","description":"The CCDC39/CCDC40 heterodimer organizes inner dynein arms, nexin-dynein regulatory and other axonemal structures. Its absence removes a network of over 90 structural proteins, including ciliary address-recognition proteins. This disrupts motility and triggers cellular effects beyond beating; these experiments support a candidate explanation for excess clinical severity without establishing longitudinal clinical mediation.","url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Ciliary_Dyskinesia.html#pathophysiology-ccdc39-ccdc40-axonemal-scaffold-loss","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3APrimary_Ciliary_Dyskinesia:pathophysiology:Impaired%20Mucociliary%20Clearance","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Mucociliary Clearance","description":"Ineffective propulsion by airway cilia, insufficient cilia number and impaired epithelial transport retain mucus and inhaled material. Radioaerosol clearance was absent in most of 69 measured patients spanning 26 genotypes, with a residual-clearance exception in CCDC103-related disease. Voluntary cough improved clearance and represents a partly compensating mechanism; regional deposition and cough complicate interpretation of whole-lung tracer measurements.","url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Ciliary_Dyskinesia.html#pathophysiology-impaired-mucociliary-clearance","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Primary_Ciliary_Dyskinesia.yaml:BCi-NS1.1 dyskinetic airway epithelial cell line","source_id":"model:kb/disorders/Primary_Ciliary_Dyskinesia.yaml:BCi-NS1.1 dyskinetic airway epithelial cell 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with outer doublet transposition.","Supports a dyskinetic ciliary phenotype in BCi-NS1.1, without establishing a PCD patient genotype."],"evidence_status":"Evidence recorded","metadata_completeness":100,"metadata_present":["Model category","NAMO class","Organism","Anatomy","Cell type","Cell source","Culture system","Modeled mechanism","Publication","Evidence"],"metadata_missing":[],"dataset_context":"Available in same 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RT-PCR of PBMC RNA from two patients corroborated c.1101-491A>G and c.867+97G>A findings. Normal retina, normal iPSC-RPE and control PBMCs established that the intron-7-retaining isoform also occurs without either variant.","notes":null,"context_id":"disorder:BEST1_Bestrophinopathies","context_kind":"Disorder","disease_name":"BEST1 Bestrophinopathies","disease_synonyms":[],"disease_term":{"id":null,"label":"BEST1 bestrophinopathy spectrum","display_label":"BEST1 bestrophinopathy spectrum","url":null},"experimental_model_type":"CELL_LINE","experimental_model_type_label":"Cell line","namo_type":"namo:CellLineModel","declared_namo_class_name":null,"namo_class_name":"CellLineModel","namo_class_label":"Cell Line Model","namo_description":"A model system based on immortalized cell lines that can be maintained in culture indefinitely. Examples: HepG2, A549, Caco-2, etc.","namo_docs_url":"https://monarch-initiative.github.io/namo/elements/CellLineModel/","namo_ontology_url":"https://w3id.org/monarch-initiative/namo/CellLineModel","namo_mapping_basis":"Safe mapping from DisMech category","namo_class_in_schema":true,"namo_schema_status":"Defined in NAMO schema used for this build","modality":"Cellular system","organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":null,"source_category":"Immortalized / cell line","culture_system":null,"publication":"PMID:37747403","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37747403","mechanisms":[{"target":"BEST1 Deep-Intronic Splice Alteration","target_url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathophysiology-best1-deep-intronic-splice-alteration","relationship":"PERTURBS","relationship_label":"Perturbs","fidelity":"NOT_SPECIFIED","fidelity_label":"Not Specified","description":null,"limitations":"Exon trapping and blood-cell RNA do not establish the quantitative splice defect in patient RPE. 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Both the canonical and longer transcripts occur in normal tissues; the variants shift their relative abundance. Minigene and patient PBMC RNA assays support splice alteration, while the predicted premature termination products and nonsense-mediated decay were not directly demonstrated at the protein or RNA-decay level. Patient RPE splice proportions remain uncertain.","url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathophysiology-best1-deep-intronic-splice-alteration","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:BEST1%20Channel%20Dysfunction","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"BEST1 Channel Dysfunction","description":"BEST1 encodes a pentameric calcium-activated anion channel of the RPE basolateral membrane. Variant effects differ: selected dominant patient-derived RPE lines have greatly reduced calcium-activated chloride currents, whereas p.Pro77Ser RPE shows increased halide permeability in a fluorescent biosensor assay. Reduced protein abundance, altered localization and channel-gating defects are allele-dependent. Dominant inheritance does not imply a uniform dominant-negative loss of channel activity.","url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathophysiology-best1-channel-dysfunction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"}],"edges":[{"id":"model-link:0:model:kb/disorders/BEST1_Bestrophinopathies.yaml:BEST1 deep-intronic variant minigenes and patient PBMC RNA","source_id":"model:kb/disorders/BEST1_Bestrophinopathies.yaml:BEST1 deep-intronic variant minigenes and patient PBMC RNA","target_id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:BEST1%20Deep-Intronic%20Splice%20Alteration","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Perturbs","directed":false,"relationship":"PERTURBS","fidelity":"NOT_SPECIFIED","causal_link_type":null,"causal_link_type_label":null,"description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ABEST1_Bestrophinopathies:6:0","source_id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:BEST1%20Deep-Intronic%20Splice%20Alteration","target_id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:BEST1%20Channel%20Dysfunction","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[6].downstream[0]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"Splice changes are expected to reduce functional BEST1 output; channel activity was not measured for these deep-intronic alleles in this study.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0}]}}],"mechanism_names":["BEST1 Deep-Intronic Splice Alteration"],"relationships":["Perturbs"],"fidelities":["Not Specified"],"biological_scales":["Molecular"],"system_context_sources":["Linked mechanism biological scale"],"modeled_system_labels":["Molecular"],"biological_process_terms":[],"biological_processes":[],"pathway_terms":[],"pathways":[],"gene_terms":[{"id":"hgnc:12703","label":"BEST1","display_label":"BEST1","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/12703"}],"genes":["BEST1"],"chemical_terms":[],"chemicals":[],"readout_names":[],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:37747403","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/37747403","reference_title":"Comprehensive Genetic Analysis Unraveled the Missing Heritability and a Founder Variant of BEST1 in a Chinese Cohort With Autosomal Recessive Bestrophinopathy.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"the aberrant products embraced an insertion of a 204-nt PE due to triggering a cryptic donor site.","explanation":"c.1101-491A>G produced a pseudoexon-containing transcript in the minigene assay, with corroboration in patient PBMC RNA; protein truncation and NMD were predicted."},{"reference":"PMID:37747403","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/37747403","reference_title":"Comprehensive Genetic Analysis Unraveled the Missing Heritability and a Founder Variant of BEST1 in a Chinese Cohort With Autosomal Recessive Bestrophinopathy.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Densitometric analysis of the minigene results (semiquantitative analysis) showed ratios of the abnormal transcript in total transcripts of 67.7%, 50.0%, and 37.5% for the DIV c.867+97G>A, c.867+97G>T, and WT constructs, respectively.","explanation":"c.867+97G>A/T increased the proportion of an intron-retaining product also produced by the wild-type construct. These semiquantitative HEK293T results are not measurements in patient RPE."}],"evidence_text":["the aberrant products embraced an insertion of a 204-nt PE due to triggering a cryptic donor site.","Densitometric analysis of the minigene results (semiquantitative analysis) showed ratios of the abnormal transcript in total transcripts of 67.7%, 50.0%, and 37.5% for the DIV c.867+97G>A, c.867+97G>T, and WT constructs, respectively.","c.1101-491A>G produced a pseudoexon-containing transcript in the minigene assay, with corroboration in patient PBMC RNA; protein truncation and NMD were predicted.","c.867+97G>A/T increased the proportion of an intron-retaining product also produced by the wild-type construct. 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Dominant inheritance does not imply a uniform dominant-negative loss of channel activity.","url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathophysiology-best1-channel-dysfunction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"}],"edges":[{"id":"model-link:1:model:kb/disorders/BEST1_Bestrophinopathies.yaml:BEST1 p.Pro233Leu and p.Pro346His polarized MDCK II model","source_id":"model:kb/disorders/BEST1_Bestrophinopathies.yaml:BEST1 p.Pro233Leu and p.Pro346His polarized MDCK II model","target_id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:Reduced%20BEST1%20Membrane%20Localization","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[1]","label":"Measures","directed":false,"relationship":"MEASURES","fidelity":"NOT_SPECIFIED","causal_link_type":null,"causal_link_type_label":null,"description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ABEST1_Bestrophinopathies:14:0","source_id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:Accelerated%20Mutant%20BEST1%20Degradation","target_id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:Reduced%20BEST1%20Membrane%20Localization","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[14].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Increased turnover reduces the pool available for membrane localization.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ABEST1_Bestrophinopathies:12:0","source_id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:Reduced%20BEST1%20Membrane%20Localization","target_id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:BEST1%20Channel%20Dysfunction","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[12].downstream[0]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"Reduced membrane abundance can impair channel activity; 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this is not a ubiquitin-chain linkage designation."},{"reference":"PMID:41456629","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41456629","reference_title":"Hsp70/CHIP E3 ligase complex triggers K149-linked ubiquitination and degradation of BEST1 mutants p.P233L and p.P346H, impairing chloride channel function and retinal integrity.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Mutant bestrophin-1 proteins p.P346H and p.P233L undergo ubiquitination and degradation, preventing their localization to the cell membrane of MDCK II cells and the RPE of zebrafish, thereby reducing chloride channel activity.","explanation":"The abstract reports degradation and mislocalization in polarized cells and zebrafish; no universal degradation mechanism across BEST1 alleles is inferred."}],"evidence_text":["Lys149 was identified as the site responsible for ubiquitination of p.P346H- and p.P233L-bestrophin-1, mediated by Hsp70 and the C-terminal Hsp70-interacting protein (CHIP).","Mutant bestrophin-1 proteins p.P346H and p.P233L undergo ubiquitination and degradation, preventing their localization to the cell membrane of MDCK II cells and the RPE of zebrafish, thereby reducing chloride channel activity.","The study identifies BEST1 residue Lys149 as the modified site for these two mutants; this is not a ubiquitin-chain linkage designation.","The abstract reports degradation and mislocalization in polarized cells and zebrafish; no universal degradation mechanism across BEST1 alleles is inferred."],"evidence_status":"Evidence recorded","metadata_completeness":50,"metadata_present":["Model category","NAMO class","Modeled mechanism","Publication","Evidence"],"metadata_missing":["Organism","Anatomy","Cell type","Cell source","Culture system"],"dataset_context":"Available in same entry","context_dataset_ids":["dataset:bioproject:prjna633668"],"candidate_dataset_ids":[],"source_path":"kb/disorders/BEST1_Bestrophinopathies.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/BEST1_Bestrophinopathies.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#experimental-model-best1-p-pro233leu-and-p-pro346his-polarized-mdck-ii-model","source_anchor":"experimental-model-best1-p-pro233leu-and-p-pro346his-polarized-mdck-ii-model"},{"id":"model:kb/disorders/BEST1_Bestrophinopathies.yaml:BEST1 p.Pro77Ser iPSC-RPE lipoplex-mediated precise editing","name":"BEST1 p.Pro77Ser iPSC-RPE lipoplex-mediated precise editing","description":"FRIMOi006-A patient-derived RPE carrying c.229C>T underwent Cas9 or Cas12 editing with a repair template, HDR enhancer and NHEJ inhibitor. Single-cell cloning and Sanger sequencing detected corrected alleles but also conversion to homozygous pathogenic sequence following wild-type allele cleavage. Morphology and RPE markers were preserved; chloride-channel rescue was not measured. Retinal-organoid delivery experiments had very low or undetectable cleavage under the tested conditions.","notes":null,"context_id":"disorder:BEST1_Bestrophinopathies","context_kind":"Disorder","disease_name":"BEST1 Bestrophinopathies","disease_synonyms":[],"disease_term":{"id":null,"label":"BEST1 bestrophinopathy spectrum","display_label":"BEST1 bestrophinopathy spectrum","url":null},"experimental_model_type":"IPSC_DERIVED_MODEL","experimental_model_type_label":"iPSC-derived model","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[{"id":"CL:0002586","label":"retinal pigment epithelial cell","display_label":"Retinal Pigment Epithelial Cell","url":"http://purl.obolibrary.org/obo/CL_0002586"}],"linked_cell_type_labels":["retinal pigment epithelial cell"],"cell_types":[{"id":"CL:0002586","label":"retinal pigment epithelial cell","display_label":"Retinal Pigment Epithelial Cell","url":"http://purl.obolibrary.org/obo/CL_0002586"}],"cell_type_labels":["retinal pigment epithelial cell"],"conditions":[],"cell_source":null,"source_category":"iPSC-derived","culture_system":null,"publication":"PMID:41827889","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41827889","mechanisms":[{"target":"BEST1 Channel Dysfunction","target_url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathophysiology-best1-channel-dysfunction","relationship":"PERTURBS","relationship_label":"Perturbs","fidelity":"NOT_SPECIFIED","fidelity_label":"Not Specified","description":null,"limitations":"The intervention changes the causal allele; the study reports DNA correction rather than functional channel rescue. Clone survival/selection affects the editing-efficiency denominator.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[{"id":"CL:0002586","label":"retinal pigment epithelial cell","display_label":"Retinal Pigment Epithelial Cell","url":"http://purl.obolibrary.org/obo/CL_0002586"}],"biological_processes":[{"id":"GO:0006821","label":"chloride transport","display_label":"Chloride Transport","url":"http://purl.obolibrary.org/obo/GO_0006821"}],"pathways":[],"genes":[{"id":"hgnc:12703","label":"BEST1","display_label":"BEST1","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/12703"}],"chemicals":[],"readouts":[],"evidence":[],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:BEST1_Bestrophinopathies","model_node_id":"model:kb/disorders/BEST1_Bestrophinopathies.yaml:BEST1 p.Pro77Ser iPSC-RPE lipoplex-mediated precise editing","focus_node_id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:BEST1%20Channel%20Dysfunction","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathograph","nodes":[{"id":"model:kb/disorders/BEST1_Bestrophinopathies.yaml:BEST1 p.Pro77Ser iPSC-RPE lipoplex-mediated precise editing","kind":"experimental_model","kind_label":"NAM model","label":"BEST1 p.Pro77Ser iPSC-RPE lipoplex-mediated precise editing","description":"FRIMOi006-A patient-derived RPE carrying c.229C>T underwent Cas9 or Cas12 editing with a repair template, HDR enhancer and NHEJ inhibitor. 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Retinal-organoid delivery experiments had very low or undetectable cleavage under the tested conditions.","url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#experimental-model-best1-p-pro77ser-ipsc-rpe-lipoplex-mediated-precise-editing","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:BEST1%20Channel%20Dysfunction","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"BEST1 Channel Dysfunction","description":"BEST1 encodes a pentameric calcium-activated anion channel of the RPE basolateral membrane. Variant effects differ: selected dominant patient-derived RPE lines have greatly reduced calcium-activated chloride currents, whereas p.Pro77Ser RPE shows increased halide permeability in a fluorescent biosensor assay. Reduced protein abundance, altered localization and channel-gating defects are allele-dependent. Dominant inheritance does not imply a uniform dominant-negative loss of channel activity.","url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathophysiology-best1-channel-dysfunction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:BEST1%20Deep-Intronic%20Splice%20Alteration","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"BEST1 Deep-Intronic Splice Alteration","description":"On NM_004183.4, c.1101-491A>G activates a cryptic donor and yields a 204-nucleotide pseudoexon. c.867+97G>A and c.867+97G>T increase use of an alternative intron-7 donor, producing a 203-nucleotide intron-retaining transcript. Both the canonical and longer transcripts occur in normal tissues; the variants shift their relative abundance. Minigene and patient PBMC RNA assays support splice alteration, while the predicted premature termination products and nonsense-mediated decay were not directly demonstrated at the protein or RNA-decay level. Patient RPE splice proportions remain uncertain.","url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathophysiology-best1-deep-intronic-splice-alteration","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:Delayed%20Photoreceptor%20Outer-Segment%20Protein%20Degradation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Delayed Photoreceptor Outer-Segment Protein Degradation","description":"Selected dominant BEST1 patient-derived iPSC-RPE models show delayed degradation of rhodopsin after photoreceptor outer-segment feeding. Wild-type BEST1 augmentation improved this endpoint in p.Arg218Cys and p.Asn296His cells but not p.Ala146Lys cells. This is a post-feeding protein-clearance readout and does not by itself measure outer-segment internalization or prove the composition of human vitelliform lesions.","url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathophysiology-delayed-photoreceptor-outer-segment-protein-degradation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:Impaired%20Photoreceptor%20Outer-Segment%20Internalization","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Photoreceptor Outer-Segment Internalization","description":"RPE differentiated from one ARB donor carrying p.Arg141His and p.Ile366fsTer18 internalized photoreceptor outer segments less efficiently than parental and unrelated control RPE. After three hours, two ARB clones internalized approximately 24% and 31% of associated outer segments versus approximately 42% in controls. This measures uptake, distinct from subsequent rhodopsin degradation. The causal contribution of reduced BEST1 abundance versus mutant-protein dysfunction was unresolved.","url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathophysiology-impaired-photoreceptor-outer-segment-internalization","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:Reduced%20BEST1%20Membrane%20Localization","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced BEST1 Membrane Localization","description":"Selected BEST1 mutants fail to accumulate normally at the membrane. This can reduce anion-channel activity, but other pathogenic alleles retain basolateral localization; preserved localization alone does not establish normal function.","url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathophysiology-reduced-best1-membrane-localization","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:Reduced%20RPE%20Transepithelial%20Fluid%20Transport","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced RPE Transepithelial Fluid Transport","description":"Patient-derived ARB iPSC-RPE monolayers showed reduced apical-to-basal fluid transport despite preserved epithelial morphology and no significant change in transepithelial electrical resistance. In a study of one ARB donor, one dominant Best disease donor and two controls, fluid flow was 0.12, 0.29 and 0.35 microliters/hour/cm2, respectively. This cellular transport defect provides a candidate explanation for fluid accumulation; the small donor sample does not establish its magnitude across BEST1 genotypes or demonstrate that epithelial barrier breakdown is required.","url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathophysiology-reduced-rpe-transepithelial-fluid-transport","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:Retinal%20Pigment%20Epithelium%20Atrophy","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Retinal Pigment Epithelium Atrophy","description":"Imaging can demonstrate loss of RPE at the macula and, in ARB, peripheral patches. Atrophy is distinct from persistent fluid and from fibrosis. The route from altered channel function and outer-segment handling to RPE cell loss remains incompletely resolved, and atrophy is not present at every disease stage.","url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathophysiology-retinal-pigment-epithelium-atrophy","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:RPE%20Apical%20Microvillar%20Underdevelopment","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"RPE Apical Microvillar Underdevelopment","description":"Recessive canine BEST1 disease shows fewer and shorter RPE apical microvilli before visible retinal lesions, with loss of cone outer-segment ensheathment and compromised interphotoreceptor matrix in established disease. These structural defects were absent in the comparator CNGB3 cone-channelopathy model. 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These are not percentages of all treated retinal cells."},{"reference":"PMID:41827889","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41827889","reference_title":"Precise CRISPR/Cas9 and Cas12 Correction Using Lipoplexes in Retinal Models Derived from Patients with Inherited Retinal Dystrophies.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"we found no off-target effects in edited clones, except in one clone in which we observed a single-nucleotide change in the experiment performed using Cas9","explanation":"Targeted Sanger screening of a few predicted sites detected one Cas9-associated off-target change; this does not exclude genome-wide off-target effects."}],"evidence_text":["the assay performed with CRISPRMAX rendered the best ratios of HDR correction and gene editing of the mutant allele resulting in 10.53% properly repaired clones, whereas only 2.63% harbored the pathogenic variant in homozygosis","we found no off-target effects in edited clones, except in one clone in which we observed a single-nucleotide change in the experiment performed using Cas9","Cas12/CRISPRMAX corrected 10.53% of screened surviving clones but also generated homozygous pathogenic clones. These are not percentages of all treated retinal cells.","Targeted Sanger screening of a few predicted sites detected one Cas9-associated off-target change; this does not exclude genome-wide off-target effects."],"evidence_status":"Evidence recorded","metadata_completeness":50,"metadata_present":["Model category","Cell type","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Organism","Anatomy","Cell source","Culture system"],"dataset_context":"Available in same entry","context_dataset_ids":["dataset:bioproject:prjna633668"],"candidate_dataset_ids":[],"source_path":"kb/disorders/BEST1_Bestrophinopathies.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/BEST1_Bestrophinopathies.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#experimental-model-best1-p-pro77ser-ipsc-rpe-lipoplex-mediated-precise-editing","source_anchor":"experimental-model-best1-p-pro77ser-ipsc-rpe-lipoplex-mediated-precise-editing"},{"id":"model:kb/disorders/BEST1_Bestrophinopathies.yaml:BEST1 p.Pro77Ser patient-derived RPE halide-permeability model","name":"BEST1 p.Pro77Ser patient-derived RPE halide-permeability model","description":"One BVMD donor was compared with two non-isogenic control lines, including a RHO-associated RP donor whose causal gene is not expressed in RPE. 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Premo halide-sensitive YFP measured iodide influx with and without A23187. BEST1 abundance/localization, short-term synthetic-bead uptake and TUNEL labeling were not significantly altered; patient cells were less pigmented.","url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#experimental-model-best1-p-pro77ser-patient-derived-rpe-halide-permeability-model","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:BEST1%20Channel%20Dysfunction","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"BEST1 Channel Dysfunction","description":"BEST1 encodes a pentameric calcium-activated anion channel of the RPE basolateral membrane. Variant effects differ: selected dominant patient-derived RPE lines have greatly reduced calcium-activated chloride currents, whereas p.Pro77Ser RPE shows increased halide permeability in a fluorescent biosensor assay. Reduced protein abundance, altered localization and channel-gating defects are allele-dependent. Dominant inheritance does not imply a uniform dominant-negative loss of channel activity.","url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathophysiology-best1-channel-dysfunction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:BEST1%20Deep-Intronic%20Splice%20Alteration","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"BEST1 Deep-Intronic Splice Alteration","description":"On NM_004183.4, c.1101-491A>G activates a cryptic donor and yields a 204-nucleotide pseudoexon. c.867+97G>A and c.867+97G>T increase use of an alternative intron-7 donor, producing a 203-nucleotide intron-retaining transcript. Both the canonical and longer transcripts occur in normal tissues; the variants shift their relative abundance. Minigene and patient PBMC RNA assays support splice alteration, while the predicted premature termination products and nonsense-mediated decay were not directly demonstrated at the protein or RNA-decay level. Patient RPE splice proportions remain uncertain.","url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathophysiology-best1-deep-intronic-splice-alteration","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:Delayed%20Photoreceptor%20Outer-Segment%20Protein%20Degradation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Delayed Photoreceptor Outer-Segment Protein Degradation","description":"Selected dominant BEST1 patient-derived iPSC-RPE models show delayed degradation of rhodopsin after photoreceptor outer-segment feeding. Wild-type BEST1 augmentation improved this endpoint in p.Arg218Cys and p.Asn296His cells but not p.Ala146Lys cells. This is a post-feeding protein-clearance readout and does not by itself measure outer-segment internalization or prove the composition of human vitelliform lesions.","url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathophysiology-delayed-photoreceptor-outer-segment-protein-degradation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:Impaired%20Photoreceptor%20Outer-Segment%20Internalization","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Photoreceptor Outer-Segment Internalization","description":"RPE differentiated from one ARB donor carrying p.Arg141His and p.Ile366fsTer18 internalized photoreceptor outer segments less efficiently than parental and unrelated control RPE. After three hours, two ARB clones internalized approximately 24% and 31% of associated outer segments versus approximately 42% in controls. This measures uptake, distinct from subsequent rhodopsin degradation. The causal contribution of reduced BEST1 abundance versus mutant-protein dysfunction was unresolved.","url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathophysiology-impaired-photoreceptor-outer-segment-internalization","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:Reduced%20BEST1%20Membrane%20Localization","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced BEST1 Membrane Localization","description":"Selected BEST1 mutants fail to accumulate normally at the membrane. This can reduce anion-channel activity, but other pathogenic alleles retain basolateral localization; preserved localization alone does not establish normal function.","url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathophysiology-reduced-best1-membrane-localization","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:Reduced%20RPE%20Transepithelial%20Fluid%20Transport","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced RPE Transepithelial Fluid Transport","description":"Patient-derived ARB iPSC-RPE monolayers showed reduced apical-to-basal fluid transport despite preserved epithelial morphology and no significant change in transepithelial electrical resistance. In a study of one ARB donor, one dominant Best disease donor and two controls, fluid flow was 0.12, 0.29 and 0.35 microliters/hour/cm2, respectively. This cellular transport defect provides a candidate explanation for fluid accumulation; the small donor sample does not establish its magnitude across BEST1 genotypes or demonstrate that epithelial barrier breakdown is required.","url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathophysiology-reduced-rpe-transepithelial-fluid-transport","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:Retinal%20Pigment%20Epithelium%20Atrophy","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Retinal Pigment Epithelium Atrophy","description":"Imaging can demonstrate loss of RPE at the macula and, in ARB, peripheral patches. Atrophy is distinct from persistent fluid and from fibrosis. The route from altered channel function and outer-segment handling to RPE cell loss remains incompletely resolved, and atrophy is not present at every disease stage.","url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathophysiology-retinal-pigment-epithelium-atrophy","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:RPE%20Apical%20Microvillar%20Underdevelopment","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"RPE Apical Microvillar Underdevelopment","description":"Recessive canine BEST1 disease shows fewer and shorter RPE apical microvilli before visible retinal lesions, with loss of cone outer-segment ensheathment and compromised interphotoreceptor matrix in established disease. 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This was a biosensor assay rather than patch-clamp chloride-current measurement."},{"reference":"PMID:35806438","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/35806438","reference_title":"Impaired Bestrophin Channel Activity in an iPSC-RPE Model of Best Vitelliform Macular Dystrophy (BVMD) from an Early Onset Patient Carrying the P77S Dominant Mutation.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We observed that the rate of phagocytosis was increased over time and there were no differences between the patient line and the control lines (Figure 6b).","explanation":"Uptake of synthetic microspheres over 4-24 hours was unchanged; this does not test long-term photoreceptor outer-segment degradation."}],"evidence_text":["These results pointed to an increased halide entrance in Fi21/01 cells both in a resting state and after calcium release by A23187.","We observed that the rate of phagocytosis was increased over time and there were no differences between the patient line and the control lines (Figure 6b).","Patient-derived p.Pro77Ser RPE showed increased iodide-sensitive YFP quenching, consistent with increased anion permeability. This was a biosensor assay rather than patch-clamp chloride-current measurement.","Uptake of synthetic microspheres over 4-24 hours was unchanged; this does not test long-term photoreceptor outer-segment degradation."],"evidence_status":"Evidence recorded","metadata_completeness":50,"metadata_present":["Model category","Cell type","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Organism","Anatomy","Cell source","Culture system"],"dataset_context":"Available in same entry","context_dataset_ids":["dataset:bioproject:prjna633668"],"candidate_dataset_ids":[],"source_path":"kb/disorders/BEST1_Bestrophinopathies.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/BEST1_Bestrophinopathies.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#experimental-model-best1-p-pro77ser-patient-derived-rpe-halide-permeability-model","source_anchor":"experimental-model-best1-p-pro77ser-patient-derived-rpe-halide-permeability-model"},{"id":"model:kb/disorders/BEST1_Bestrophinopathies.yaml:BEST1 patient-derived iPSC-RPE augmentation and allele-selective editing","name":"BEST1 patient-derived iPSC-RPE augmentation and allele-selective editing","description":"Three dominant lines carried p.Arg218Cys, p.Asn296His or p.Ala146Lys; the ARB line carried p.Arg141His/p.Ala195Val. Controls included unaffected RPE and an isogenic corrected p.Arg218Cys line. Lentiviral VMD2-driven BEST1 augmentation restored chloride currents in the ARB line and two dominant lines, but not p.Ala146Lys. Mutant-allele-selective CRISPR-Cas9 disruption restored currents in all three dominant lines. Transcriptomic testing found no adverse RPE program changes, but targeted sequencing detected an off-target noncoding chromosome 7 alteration with the p.Arg218Cys guide.","notes":null,"context_id":"disorder:BEST1_Bestrophinopathies","context_kind":"Disorder","disease_name":"BEST1 Bestrophinopathies","disease_synonyms":[],"disease_term":{"id":null,"label":"BEST1 bestrophinopathy spectrum","display_label":"BEST1 bestrophinopathy spectrum","url":null},"experimental_model_type":"IPSC_DERIVED_MODEL","experimental_model_type_label":"iPSC-derived model","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[{"id":"CL:0002586","label":"retinal pigment epithelial cell","display_label":"Retinal Pigment Epithelial Cell","url":"http://purl.obolibrary.org/obo/CL_0002586"}],"linked_cell_type_labels":["retinal pigment epithelial cell"],"cell_types":[{"id":"CL:0002586","label":"retinal pigment epithelial cell","display_label":"Retinal Pigment Epithelial Cell","url":"http://purl.obolibrary.org/obo/CL_0002586"}],"cell_type_labels":["retinal pigment epithelial cell"],"conditions":[],"cell_source":null,"source_category":"iPSC-derived","culture_system":null,"publication":"PMID:32707085","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32707085","mechanisms":[{"target":"BEST1 Channel Dysfunction","target_url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathophysiology-best1-channel-dysfunction","relationship":"PERTURBS","relationship_label":"Perturbs","fidelity":"NOT_SPECIFIED","fidelity_label":"Not Specified","description":null,"limitations":"Lentiviral gene delivery in cultured RPE, not the AAV clinical-trial construct; rescue is allele- and assay-specific. 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Transcriptomic testing found no adverse RPE program changes, but targeted sequencing detected an off-target noncoding chromosome 7 alteration with the p.Arg218Cys guide.","url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#experimental-model-best1-patient-derived-ipsc-rpe-augmentation-and-allele-selective-editing","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:BEST1%20Channel%20Dysfunction","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"BEST1 Channel Dysfunction","description":"BEST1 encodes a pentameric calcium-activated anion channel of the RPE basolateral membrane. Variant effects differ: selected dominant patient-derived RPE lines have greatly reduced calcium-activated chloride currents, whereas p.Pro77Ser RPE shows increased halide permeability in a fluorescent biosensor assay. Reduced protein abundance, altered localization and channel-gating defects are allele-dependent. Dominant inheritance does not imply a uniform dominant-negative loss of channel activity.","url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathophysiology-best1-channel-dysfunction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:BEST1%20Deep-Intronic%20Splice%20Alteration","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"BEST1 Deep-Intronic Splice Alteration","description":"On NM_004183.4, c.1101-491A>G activates a cryptic donor and yields a 204-nucleotide pseudoexon. c.867+97G>A and c.867+97G>T increase use of an alternative intron-7 donor, producing a 203-nucleotide intron-retaining transcript. Both the canonical and longer transcripts occur in normal tissues; the variants shift their relative abundance. Minigene and patient PBMC RNA assays support splice alteration, while the predicted premature termination products and nonsense-mediated decay were not directly demonstrated at the protein or RNA-decay level. Patient RPE splice proportions remain uncertain.","url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathophysiology-best1-deep-intronic-splice-alteration","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:Delayed%20Photoreceptor%20Outer-Segment%20Protein%20Degradation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Delayed Photoreceptor Outer-Segment Protein Degradation","description":"Selected dominant BEST1 patient-derived iPSC-RPE models show delayed degradation of rhodopsin after photoreceptor outer-segment feeding. Wild-type BEST1 augmentation improved this endpoint in p.Arg218Cys and p.Asn296His cells but not p.Ala146Lys cells. This is a post-feeding protein-clearance readout and does not by itself measure outer-segment internalization or prove the composition of human vitelliform lesions.","url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathophysiology-delayed-photoreceptor-outer-segment-protein-degradation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:Impaired%20Photoreceptor%20Outer-Segment%20Internalization","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Photoreceptor Outer-Segment Internalization","description":"RPE differentiated from one ARB donor carrying p.Arg141His and p.Ile366fsTer18 internalized photoreceptor outer segments less efficiently than parental and unrelated control RPE. After three hours, two ARB clones internalized approximately 24% and 31% of associated outer segments versus approximately 42% in controls. This measures uptake, distinct from subsequent rhodopsin degradation. The causal contribution of reduced BEST1 abundance versus mutant-protein dysfunction was unresolved.","url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathophysiology-impaired-photoreceptor-outer-segment-internalization","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:Reduced%20BEST1%20Membrane%20Localization","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced BEST1 Membrane Localization","description":"Selected BEST1 mutants fail to accumulate normally at the membrane. This can reduce anion-channel activity, but other pathogenic alleles retain basolateral localization; preserved localization alone does not establish normal function.","url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathophysiology-reduced-best1-membrane-localization","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:Reduced%20RPE%20Transepithelial%20Fluid%20Transport","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced RPE Transepithelial Fluid Transport","description":"Patient-derived ARB iPSC-RPE monolayers showed reduced apical-to-basal fluid transport despite preserved epithelial morphology and no significant change in transepithelial electrical resistance. In a study of one ARB donor, one dominant Best disease donor and two controls, fluid flow was 0.12, 0.29 and 0.35 microliters/hour/cm2, respectively. This cellular transport defect provides a candidate explanation for fluid accumulation; the small donor sample does not establish its magnitude across BEST1 genotypes or demonstrate that epithelial barrier breakdown is required.","url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathophysiology-reduced-rpe-transepithelial-fluid-transport","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:Retinal%20Pigment%20Epithelium%20Atrophy","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Retinal Pigment Epithelium Atrophy","description":"Imaging can demonstrate loss of RPE at the macula and, in ARB, peripheral patches. Atrophy is distinct from persistent fluid and from fibrosis. The route from altered channel function and outer-segment handling to RPE cell loss remains incompletely resolved, and atrophy is not present at every disease stage.","url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathophysiology-retinal-pigment-epithelium-atrophy","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:RPE%20Apical%20Microvillar%20Underdevelopment","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"RPE Apical Microvillar Underdevelopment","description":"Recessive canine BEST1 disease shows fewer and shorter RPE apical microvilli before visible retinal lesions, with loss of cone outer-segment ensheathment and compromised interphotoreceptor matrix in established disease. 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It does not establish that these changes cause ciliary dysfunction or characterize all PCD genotypes."}]}],"findings_text":["BMI1-expanded DNAH5 cultures show altered ion-channel activity relative to non-PCD cultures; its relationship to immotility remains exploratory."],"evidence":[{"reference":"PMID:41064994","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41064994","reference_title":"Characterisation of a primary ciliary dyskinesia model generated from BMI1-transduced basal epithelial cells.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We report that the cells retain their proliferation and differentiation capacity for at least 19 passages and recapitulate the disease phenotype with immotile cilia lacking DNAH5 and other outer dynein arm proteins.","explanation":"Supports prolonged expansion and retention of the DNAH5 outer-dynein-arm defect; it does not establish fidelity for motile, normal-TEM PCD genotypes."},{"reference":"PMID:41064994","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41064994","reference_title":"Characterisation of a primary ciliary dyskinesia model generated from BMI1-transduced basal epithelial cells.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Characterisation of the ion transport properties of these PCD cells grown at an air-liquid interface showed lower activity of the Na+ channel ENaC and enhanced CFTR activity compared to non-PCD cells, which might be linked to ciliary immotility.","explanation":"The two-donor model study reports lower ENaC and higher CFTR activity. 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splicing.","Differentiation to induced neural crest cells is defective, with a delay in undergoing the epithelial-to-mesenchymal transition."],"evidence":[{"reference":"PMID:32735620","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/32735620","reference_title":"Modelling the developmental spliceosomal craniofacial disorder Burn-McKeown syndrome using induced pluripotent stem cells.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Here we reprogrammed peripheral mononuclear blood cells from a BMKS patient and her unaffected mother into induced pluripotent stem cells (iPSCs) and differentiated the iPSCs into induced neural crest cells (iNCCs), the key cell type required for correct craniofacial development.","explanation":"Describes the patient-derived cellular model and its maternal control, the principal experimental system for BMKS mechanism."},{"reference":"PMID:32735620","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/32735620","reference_title":"Modelling the developmental spliceosomal craniofacial disorder Burn-McKeown syndrome using induced pluripotent stem cells.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"rMATS identified 2991 differential splicing events in 2029 different genes","explanation":"Neural crest-stage result."},{"reference":"PMID:32735620","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/32735620","reference_title":"Modelling the developmental spliceosomal craniofacial disorder Burn-McKeown syndrome using induced pluripotent stem cells.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The patient iNCCs had a score of -5, while the mother iNCCs had an EMT score of +5 and the unrelated controls had an EMT score of +8","explanation":"EMT state differs among these lines."},{"reference":"PMID:32735620","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/32735620","reference_title":"Modelling the developmental spliceosomal craniofacial disorder Burn-McKeown syndrome using induced pluripotent stem 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crest-stage result.","EMT state differs among these lines.","Measured response in the induction protocol."],"evidence_status":"Evidence recorded","metadata_completeness":80,"metadata_present":["Model category","Organism","Cell type","Cell source","Culture system","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Anatomy"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Burn-McKeown_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Burn-McKeown_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Burn-McKeown_Syndrome.html#experimental-model-bmks-patient-derived-ipsc-induced-neural-crest-cells","source_anchor":"experimental-model-bmks-patient-derived-ipsc-induced-neural-crest-cells"},{"id":"model:kb/disorders/Botulism.yaml:BoNT/A-exposed human iPSC-derived 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BoNT/A and E target SNAP-25, whereas BoNT/B and several other serotypes target VAMP/synaptobrevin; substrate and cleavage-site specificity vary by toxin.","url":"https://dismech.monarchinitiative.org/pages/disorders/Botulism.html#pathophysiology-serotype-specific-snare-proteolysis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ABotulism:pathophysiology:Alternative%20retrograde%20Golgi-ER%20trafficking%20in%20RenVM%20neurons","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Alternative retrograde Golgi-ER trafficking in RenVM neurons","description":"In genetically engineered RenVM neurons, BoNT/A activity first appeared in the soma; perturbation and complementation experiments supported retromer-dependent trafficking through Golgi and ER and an apparent Sec61-associated cytosolic exit. 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analysis the effects of BoNT/A and a catalytically inactive derivative (BoNT/A ad) on the transcriptome of human induced pluripotent stem cell (hiPSC)-derived neurons at 2 days and 2 weeks after exposure.","The flaccid paralysis is due to specific cleavage of neuronal SNAREs by BoNTs.","The source directly describes the human neuronal exposure model and time points.","The publication explicitly situates its exposure model in the SNARE-cleavage mechanism."],"evidence_status":"Evidence recorded","metadata_completeness":80,"metadata_present":["Model category","Organism","Cell type","Cell source","Culture system","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Anatomy"],"dataset_context":"Available in same 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This is the standard ex vivo preparation in the ergot-alkaloid vascular literature, and the study cited here uses it to establish which serotonin receptor subtypes the vessel carries and what each does - the receptor repertoire that the ergoline agonism node acts on.","notes":"Cited for the vessel's receptor pharmacology, not for ergot action. The study's agonists are serotonin itself and subtype-selective 5-HT agonists; no ergot alkaloid was applied. The deep-research report listed this preparation among ergot-alkaloid model systems, which overstates what this particular paper shows, and the `divergences` block below records that rather than repeating it.","context_id":"disorder:Ergotism","context_kind":"Disorder","disease_name":"Ergotism","disease_synonyms":["ergot poisoning","ergot alkaloid toxicity","ergotoxicosis","St Anthony's Fire","Saint Anthony's Fire","ignis sacer","holy fire"],"disease_term":{"id":"MONDO:0042496","label":"ergotism","display_label":"ergotism","url":"http://purl.obolibrary.org/obo/MONDO_0042496"},"experimental_model_type":"OTHER","experimental_model_type_label":"Other","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":{"id":"NCBITaxon:9913","label":"Bos taurus","display_label":"cattle","url":"http://purl.obolibrary.org/obo/NCBITaxon_9913"},"organism_label":"Bos taurus","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":null,"source_category":null,"culture_system":null,"publication":"PMID:38946059","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38946059","mechanisms":[{"target":"Ergoline Agonism at Vascular 5-HT and Alpha-Adrenergic Receptors","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Ergotism.html#pathophysiology-ergoline-agonism-at-vascular-5-ht-and-alpha-adrenergic-receptors","relationship":"MEASURES","relationship_label":"Measures","fidelity":"LOW","fidelity_label":"Low","description":"Establishes which 5-HT receptor subtypes are present and functional in a peripheral vein, and that most of the relaxing response runs through 5-HT4 - the pharmacological background against which an ergoline's mixed agonism at this node has to be read.","limitations":"No ergot alkaloid was applied in this study, so it cannot show ergoline action at these receptors; it characterises the receptors. It also reads out vasorelaxation, the opposite direction from the contraction this entry's chain runs through, and it is a vein rather than the peripheral artery where the human lesion forms.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0007210","label":"serotonin receptor signaling pathway","display_label":"serotonin receptor signaling driven by ergot alkaloid agonism","url":"http://purl.obolibrary.org/obo/GO_0007210"},{"id":"GO:0071875","label":"adrenergic receptor signaling pathway","display_label":"adrenergic receptor signaling driven by ergot alkaloid agonism","url":"http://purl.obolibrary.org/obo/GO_0071875"}],"pathways":[],"genes":[],"chemicals":[{"id":"CHEBI:64318","label":"ergotamine","display_label":"ergotamine","url":"http://purl.obolibrary.org/obo/CHEBI_64318"}],"readouts":[],"evidence":[{"reference":"PMID:38946059","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38946059","reference_title":"Serotonin receptor-mediated vasorelaxation occurs primarily through 5-HT(4) activation in bovine lateral saphenous vein.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Approximately 94% of the vasorelaxation occurring in response to 5-HT could be accounted for through 5-HT4, providing strong evidence that 5-HT-mediated vasorelaxation occurs through 5-HT4 activation in bovine peripheral vasculature.","explanation":"The receptor-subtype result this preparation contributes, which is what it is cited for."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Ergotism","model_node_id":"model:kb/disorders/Ergotism.yaml:Bovine lateral saphenous vein myography","focus_node_id":"node:disorder%3AErgotism:pathophysiology:Ergoline%20Agonism%20at%20Vascular%205-HT%20and%20Alpha-Adrenergic%20Receptors","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Ergotism.html#pathograph","nodes":[{"id":"model:kb/disorders/Ergotism.yaml:Bovine lateral saphenous vein myography","kind":"experimental_model","kind_label":"NAM model","label":"Bovine lateral saphenous vein myography","description":"Isolated lateral saphenous vein rings from cattle mounted for myography. 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Dihydroergotamine binds serotonin receptors in the dorsal horn of the spinal cord, which is where the neuropathological changes of convulsive ergotism are found. The clinical picture - twitching, spasm, altered mental state, hallucination, sweating and fever over weeks - is the picture of serotonergic overstimulation, and dihydroergotamine given to people can produce serotonin syndrome outright.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ergotism.html#pathophysiology-central-serotonergic-overstimulation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AErgotism:pathophysiology:CYP3A4%20Inhibition%20Raising%20Systemic%20Ergotamine%20Concentration","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"CYP3A4 Inhibition Raising Systemic Ergotamine Concentration","description":"The step that makes ergotism a live problem in countries with clean grain. Ergotamine is destroyed on first pass through the liver by CYP3A4, leaving under 5% oral bioavailability - which is why an ordinary migraine dose is tolerated at all. A strong CYP3A4 inhibitor removes that first-pass barrier, and the same tablet delivers a toxic plasma concentration. The inhibitors implicated are the HIV protease inhibitors, the pharmacokinetic booster cobicistat, and the macrolide antibiotics.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ergotism.html#pathophysiology-cyp3a4-inhibition-raising-systemic-ergotamine-concentration","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AErgotism:pathophysiology:Ergot%20Alkaloid%20Entry%20into%20the%20Circulation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Ergot Alkaloid Entry into the Circulation","description":"The exposure event, reached by two routes that differ in everything except what arrives in the blood. Contaminated grain delivers a mixture of the alkaloids a particular Claviceps strain happens to make; a prescription delivers one purified alkaloid at a known dose. The alkaloid composition of the mixture is not constant, which matters because it is what decided whether a historical epidemic was gangrenous or convulsive.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ergotism.html#pathophysiology-ergot-alkaloid-entry-into-the-circulation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AErgotism:pathophysiology:Sustained%20Vascular%20Smooth%20Muscle%20Contraction","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Sustained Vascular Smooth Muscle Contraction","description":"What separates ergot vasoconstriction from ordinary vasoconstriction is how long it lasts. In an arterial tissue bath a single dose of ergocristine produced contraction sustained across a three-hour incubation, and the response persists well beyond the point at which the alkaloid would have been cleared. That persistence is why the clinical syndrome is a spasm that resists reversal rather than a transient squeeze, and why case reports describe failure of first-line vasodilators.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ergotism.html#pathophysiology-sustained-vascular-smooth-muscle-contraction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Ergotism.yaml:Bovine lateral saphenous vein myography","source_id":"model:kb/disorders/Ergotism.yaml:Bovine lateral saphenous vein myography","target_id":"node:disorder%3AErgotism:pathophysiology:Ergoline%20Agonism%20at%20Vascular%205-HT%20and%20Alpha-Adrenergic%20Receptors","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Measures","directed":false,"relationship":"MEASURES","fidelity":"LOW","causal_link_type":null,"causal_link_type_label":null,"description":"Establishes which 5-HT receptor subtypes are present and functional in a peripheral vein, and that most of the relaxing response runs through 5-HT4 - the pharmacological background against which an ergoline's mixed agonism at this node has to be read.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AErgotism:1:0","source_id":"node:disorder%3AErgotism:pathophysiology:CYP3A4%20Inhibition%20Raising%20Systemic%20Ergotamine%20Concentration","target_id":"node:disorder%3AErgotism:pathophysiology:Ergoline%20Agonism%20at%20Vascular%205-HT%20and%20Alpha-Adrenergic%20Receptors","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"The raised plasma concentration is what drives receptor occupancy high enough to be toxic. 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Human anemia and thrombocytopenia have been observed without establishing this severe stem-cell failure mechanism.","url":"https://dismech.monarchinitiative.org/pages/disorders/BRPF1-Related_Intellectual_Disability.html#pathophysiology-impaired-hematopoietic-stem-and-progenitor-cell-maintenance","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ABRPF1-Related_Intellectual_Disability:pathophysiology:Altered%20Developmental%20Transcriptional%20Programs","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Altered Developmental Transcriptional Programs","description":"BRPF1 perturbation changes developmental gene expression in a context-dependent manner. Human embryonic stem-cell deletion suppresses stemness genes and activates lineage genes. 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In zebrafish mutants, anterior Hox expression is initiated normally but subsequently lost in cranial neural crest; this contrasts with elevated Hox expression after mouse forebrain deletion and illustrates tissue-dependent directionality.","url":"https://dismech.monarchinitiative.org/pages/disorders/BRPF1-Related_Intellectual_Disability.html#pathophysiology-altered-developmental-transcriptional-programs","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ABRPF1-Related_Intellectual_Disability:phenotype:Anemia","kind":"phenotype","kind_label":"Phenotype","label":"Anemia","description":"Anemia was reported in a family with a BRPF1 nonsense variant and subsequently in one of 25 assessed patients in the 2025 cohort. The latter report found no evidence of bone marrow damage. 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In the hESC knockout study, H3K4me3 persisted and H3K14ac was initially preserved before declining with differentiation; direct H3K4me3 recognition by BRPF1 was not biochemically resolved.","url":"https://dismech.monarchinitiative.org/pages/disorders/BRPF1-Related_Intellectual_Disability.html#pathophysiology-deficient-histone-h3k23-acetylation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ABRPF1-Related_Intellectual_Disability:pathophysiology:Altered%20Chromatin%20Accessibility","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Altered Chromatin Accessibility","description":"Complete BRPF1 deletion in human H1 embryonic stem cells reduces ATAC-seq accessibility at stemness genes while increasing accessibility at lineage-associated genes. H3K4me3 remains substantially present despite loss of H3K23ac and pluripotency. 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Developmental transcript changes accompany these abnormalities, but specific transcriptional mediators have not been isolated by rescue. The severe conditional-null model is not equivalent to heterozygous human disease.","url":"https://dismech.monarchinitiative.org/pages/disorders/BRPF1-Related_Intellectual_Disability.html#pathophysiology-aberrant-cortical-neurogenesis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ABRPF1-Related_Intellectual_Disability:pathophysiology:Abnormal%20Corpus%20Callosum%20Development","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Abnormal Corpus Callosum Development","description":"Conditional homozygous Brpf1 loss in the embryonic forebrain produces partial callosal agenesis in mice. Conditional heterozygotes in a separate study have a modest reduction in callosal thickness. These zygosity-dependent anatomical changes provide model evidence, while the route to rare human agenesis or hypoplasia remains unproven.","url":"https://dismech.monarchinitiative.org/pages/disorders/BRPF1-Related_Intellectual_Disability.html#pathophysiology-abnormal-corpus-callosum-development","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ABRPF1-Related_Intellectual_Disability:pathophysiology:Altered%20Chromatin%20Accessibility","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Altered Chromatin Accessibility","description":"Complete BRPF1 deletion in human H1 embryonic stem cells reduces ATAC-seq accessibility at stemness genes while increasing accessibility at lineage-associated genes. H3K4me3 remains substantially present despite loss of H3K23ac and pluripotency. Co-occupancy and rescue support BRPF1-dependent chromatin regulation, but the biochemical route from H3K23ac loss to accessibility change and its applicability to heterozygous patient neurons remain unresolved.","url":"https://dismech.monarchinitiative.org/pages/disorders/BRPF1-Related_Intellectual_Disability.html#pathophysiology-altered-chromatin-accessibility","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ABRPF1-Related_Intellectual_Disability:phenotype:Congenital%20Cardiac%20Anomalies","kind":"phenotype","kind_label":"Phenotype","label":"Congenital Cardiac Anomalies","description":"Cardiac malformations occur in a minority of BRPF1 patients. Reported anomalies include patent ductus arteriosus and atrial or ventricular septal defects.","url":"https://dismech.monarchinitiative.org/pages/disorders/BRPF1-Related_Intellectual_Disability.html#phenotype-congenital-cardiac-anomalies","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ABRPF1-Related_Intellectual_Disability:pathophysiology:Deficient%20Histone%20H3K23%20Propionylation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Deficient Histone H3K23 Propionylation","description":"BRPF1-KAT6 complexes propionylate H3K23. Several patient variants impair this activity, and the mark is reduced in Pro370Ser lymphoblastoid cells and Arg455Ter lymphoblastoid cells and fibroblasts. Complete Brpf1 deletion abolishes detectable H3K23 propionylation in mouse embryos and cultured fibroblasts. Effects are allele- and assay-dependent: Pro76Leu retained stimulation in the biochemical assay, and some truncating products also retained activity. The independent contribution of propionylation loss to the human phenotype is unresolved.","url":"https://dismech.monarchinitiative.org/pages/disorders/BRPF1-Related_Intellectual_Disability.html#pathophysiology-deficient-histone-h3k23-propionylation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ABRPF1-Related_Intellectual_Disability:pathophysiology:Deregulated%20Ocular%20and%20Periocular%20Developmental%20Transcription%20Factor%20Programs","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Deregulated Ocular and Periocular Developmental Transcription Factor Programs","description":"BRPF1-dependent regulation of Pitx2, Hmx1 and Pax6 has been proposed as a route to the ocular and periocular phenotype. The cited clinical cohort extrapolates from developmental-model literature; it does not directly test these transcription factors in human periocular tissue. The connection to ptosis, blepharophimosis and ocular alignment remains hypothetical.","url":"https://dismech.monarchinitiative.org/pages/disorders/BRPF1-Related_Intellectual_Disability.html#pathophysiology-deregulated-ocular-and-periocular-developmental-transcription-factor-programs","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"HYPOTHETICAL","mechanism_confidence_label":"Hypothetical"},{"id":"node:disorder%3ABRPF1-Related_Intellectual_Disability:phenotype:Global%20Developmental%20Delay","kind":"phenotype","kind_label":"Phenotype","label":"Global Developmental Delay","description":"Global developmental delay affecting motor, language and adaptive domains is the presenting feature in most reported individuals, and was the reason for ascertainment in the founding series.","url":"https://dismech.monarchinitiative.org/pages/disorders/BRPF1-Related_Intellectual_Disability.html#phenotype-global-developmental-delay","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ABRPF1-Related_Intellectual_Disability:pathophysiology:Impaired%20Axonal%20Outgrowth","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Axonal Outgrowth","description":"Primary cortical neurons from E16.5 Emx1-lineage Brpf1 conditional heterozygotes have shorter Tau-positive axons at DIV5; conditional homozygous deletion produces a larger reduction. This culture phenotype does not by itself explain callosal anatomy or human cognitive impairment.","url":"https://dismech.monarchinitiative.org/pages/disorders/BRPF1-Related_Intellectual_Disability.html#pathophysiology-impaired-axonal-outgrowth","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ABRPF1-Related_Intellectual_Disability:pathophysiology:Impaired%20Dendritic%20Arborization","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Dendritic Arborization","description":"Emx1-lineage conditional Brpf1 heterozygous mice have reduced dendritic branching in dentate granule cells and layer V cortical pyramidal neurons. E16.5 cortical cultures also show shorter and less complex dendrites at DIV14. Conditional homozygous loss produces more severe changes. These observations concern mouse neurons; they do not establish a human neuronal phenotype or a transcriptional mediator.","url":"https://dismech.monarchinitiative.org/pages/disorders/BRPF1-Related_Intellectual_Disability.html#pathophysiology-impaired-dendritic-arborization","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ABRPF1-Related_Intellectual_Disability:pathophysiology:Impaired%20Hematopoietic%20Stem%20and%20Progenitor%20Cell%20Maintenance","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Hematopoietic Stem and Progenitor Cell Maintenance","description":"Hematopoietic Vav1-iCre Brpf1 homozygous deletion impairs fetal stem/progenitor function and causes progressive postnatal marrow failure in mice. The phenotype includes loss of repopulating capacity despite preserved marrow homing, reduced neonatal LSK proliferation, and increased apoptosis, oxidative stress and senescence. Fetal LSK proliferation is initially preserved. Conditional heterozygotes have unchanged survival and neonatal LSK-cell numbers in the reported tests. Human anemia and thrombocytopenia have been observed without establishing this severe stem-cell failure mechanism.","url":"https://dismech.monarchinitiative.org/pages/disorders/BRPF1-Related_Intellectual_Disability.html#pathophysiology-impaired-hematopoietic-stem-and-progenitor-cell-maintenance","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ABRPF1-Related_Intellectual_Disability:phenotype:Infantile%20Hypotonia","kind":"phenotype","kind_label":"Phenotype","label":"Infantile Hypotonia","description":"Hypotonia with infantile onset is a core feature, contributing to early motor delay and to feeding difficulty. The cited cohort documents improvement in motor delay, but does not separately establish the course of hypotonia.","url":"https://dismech.monarchinitiative.org/pages/disorders/BRPF1-Related_Intellectual_Disability.html#phenotype-infantile-hypotonia","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ABRPF1-Related_Intellectual_Disability:pathophysiology:Reduced%20Dendritic%20Spine%20Density%20and%20Altered%20Spine%20Morphology","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced Dendritic Spine Density and Altered Spine Morphology","description":"Conditional Emx1-lineage Brpf1 heterozygous mice have fewer and longer spines on cortical pyramidal-neuron apical dendrites. Homozygous conditional loss has a more severe effect. Hippocampal CA3 electron microscopy separately shows lower synaptic density, smaller postsynaptic densities and narrower synaptic clefts. Spine and synaptic measurements accompany electrophysiological changes but were not selectively rescued to demonstrate mediation.","url":"https://dismech.monarchinitiative.org/pages/disorders/BRPF1-Related_Intellectual_Disability.html#pathophysiology-reduced-dendritic-spine-density-and-altered-spine-morphology","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ABRPF1-Related_Intellectual_Disability:pathophysiology:Reduced%20Inhibitory%20Neurotransmission%20in%20GABAergic%20Interneurons","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced Inhibitory Neurotransmission in GABAergic Interneurons","description":"Partial Brpf1 knockdown in cultured mouse MGE-derived GABAergic interneurons reduced miniature inhibitory postsynaptic current amplitude without a significant change in frequency. This synaptic readout is distinct from the intrinsic excitability changes measured in the same cultures. Dendritic morphology and transplanted-cell cortical distribution were not significantly altered under the tested conditions. The findings do not establish a human circuit-level excitation/inhibition ratio or a causal route to seizures.","url":"https://dismech.monarchinitiative.org/pages/disorders/BRPF1-Related_Intellectual_Disability.html#pathophysiology-reduced-inhibitory-neurotransmission-in-gabaergic-interneurons","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ABRPF1-Related_Intellectual_Disability:pathophysiology:Reduced%20Intrinsic%20Excitability%20of%20Hippocampal%20Pyramidal%20Neurons","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced Intrinsic Excitability of Hippocampal Pyramidal Neurons","description":"CA1 pyramidal neurons in acute slices from Emx1-lineage conditional Brpf1 heterozygotes have lower input resistance, a higher current threshold for firing and fewer spikes at selected current steps, while resting membrane potential is unchanged. These effects are distinct from mEPSC changes and were not observed in the separate mild hippocampal shRNA culture study.","url":"https://dismech.monarchinitiative.org/pages/disorders/BRPF1-Related_Intellectual_Disability.html#pathophysiology-reduced-intrinsic-excitability-of-hippocampal-pyramidal-neurons","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ABRPF1-Related_Intellectual_Disability:pathophysiology:Reduced%20Intrinsic%20Excitability%20of%20MGE-Derived%20GABAergic%20Interneurons","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced Intrinsic Excitability of MGE-Derived GABAergic Interneurons","description":"In cultured mouse MGE-derived interneurons, partial Brpf1 knockdown increased the injected-current threshold required to evoke action potentials and reduced spike counts at selected current steps. Resting membrane potential and maximum evoked firing frequency were unchanged. These cell-intrinsic responses are experimentally distinct from the reduced mIPSC amplitude and have not been tested as a cause of human cognitive or seizure phenotypes.","url":"https://dismech.monarchinitiative.org/pages/disorders/BRPF1-Related_Intellectual_Disability.html#pathophysiology-reduced-intrinsic-excitability-of-mge-derived-gabaergic-interneurons","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ABRPF1-Related_Intellectual_Disability:phenotype:Speech%20and%20Language%20Disorder","kind":"phenotype","kind_label":"Phenotype","label":"Speech and Language Disorder","description":"Speech and language difficulties are prominent but variably recorded. The dedicated speech-language study found mostly mild-to-moderate deficits across receptive, expressive, written and social-pragmatic domains; phonological delay and disorder were common speech diagnoses. Formal assessment of language disorder and a history of delayed speech milestones are related but distinct endpoints.","url":"https://dismech.monarchinitiative.org/pages/disorders/BRPF1-Related_Intellectual_Disability.html#phenotype-speech-and-language-disorder","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:3:model:kb/disorders/BRPF1-Related_Intellectual_Disability.yaml:BRPF1-null human H1 embryonic stem cells with inducible rescue","source_id":"model:kb/disorders/BRPF1-Related_Intellectual_Disability.yaml:BRPF1-null human H1 embryonic stem cells with inducible 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human neuronal causation is untested."}],"evidence_text":["CARP2 interacts and mono-ubiquitinates STUB1.","pathogenic mutants of STUB1 are more prone than the wild-type to CARP2-mediated aggregate assembly.","Experimental interaction and modification of CHIP by CARP2.","CARP2 modifies mutant CHIP and promotes aggregate assembly in experimental systems; human neuronal causation is untested."],"evidence_status":"Evidence recorded","metadata_completeness":50,"metadata_present":["Model category","NAMO class","Modeled mechanism","Publication","Evidence"],"metadata_missing":["Organism","Anatomy","Cell type","Cell source","Culture system"],"dataset_context":"Available in same entry","context_dataset_ids":["dataset:geo:gse310700","dataset:https://ngdc.cncb.ac.cn/omix/release/omix008238"],"candidate_dataset_ids":[],"source_path":"kb/disorders/Autosomal_Recessive_Spinocerebellar_Ataxia_16.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autosomal_Recessive_Spinocerebellar_Ataxia_16.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Recessive_Spinocerebellar_Ataxia_16.html#experimental-model-carp-dependent-chip-sequestration-in-hek293t-and-n2a-cells","source_anchor":"experimental-model-carp-dependent-chip-sequestration-in-hek293t-and-n2a-cells"},{"id":"model:kb/disorders/RAB23-Related_Carpenter_Syndrome.yaml:Carpenter syndrome patient-derived iPSC neural lineage","name":"Carpenter syndrome patient-derived iPSC neural lineage","description":"Induced pluripotent stem cells from Carpenter syndrome patients, differentiated down the neural lineage. This is the only human-cell system in the entry, and it is what turns \"Carpenter syndrome resembles a ciliopathy\" into a measurement in patient cells rather than an inference from mouse work.\nIts most useful result is a dissociation within one genotype. Neurons differentiated from these lines show a marked drop in the proportion of ciliated cells, while the same patients' fibroblasts, undifferentiated iPSCs and neural progenitors keep a normal ciliation rate and show only shortened cilia. A study that had sampled fibroblasts alone would have concluded the ciliary defect was mild.","notes":null,"context_id":"disorder:RAB23-Related_Carpenter_Syndrome","context_kind":"Disorder","disease_name":"RAB23-related Carpenter Syndrome","disease_synonyms":["Carpenter syndrome 1","CRPT1","Carpenter syndrome","acrocephalopolysyndactyly type II","RAB23-associated Carpenter syndrome"],"disease_term":{"id":"MONDO:0008710","label":"RAB23-related Carpenter syndrome","display_label":"RAB23-related Carpenter syndrome","url":"http://purl.obolibrary.org/obo/MONDO_0008710"},"experimental_model_type":"IPSC_DERIVED_MODEL","experimental_model_type_label":"iPSC-derived model","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":null,"source_category":"iPSC-derived","culture_system":null,"publication":null,"publication_url":null,"mechanisms":[{"target":"Impaired Ciliary Protein Trafficking","target_url":"https://dismech.monarchinitiative.org/pages/disorders/RAB23-related_Carpenter_Syndrome.html#pathophysiology-impaired-ciliary-protein-trafficking","relationship":"RECAPITULATES","relationship_label":"Recapitulates","fidelity":"HIGH","fidelity_label":"High","description":"Patient cells carrying patient alleles, assayed for the ciliary phenotype this node asserts, with the cell-type dependence measured rather than assumed.","limitations":"Differentiated cells in culture, not developing tissue. The lineages assayed are neural, so nothing here speaks to the cranial suture or limb bud, which are where the defining features of the disease arise.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0061512","label":"protein localization to cilium","display_label":"protein localization to cilium","url":"http://purl.obolibrary.org/obo/GO_0061512"},{"id":"GO:0060271","label":"cilium assembly","display_label":"cilium assembly","url":"http://purl.obolibrary.org/obo/GO_0060271"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Ciliation frequency in iPSC-derived neurons","description":null,"target":"Impaired Ciliary Protein Trafficking","direction":"DECREASED","interpretation":"The proportion of ciliated cells falls in patient-derived neurons specifically.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:40825043","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40825043","reference_title":"RAB23 loss-of-function mutation causes context-dependent ciliopathy in Carpenter syndrome.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"A profound reduction in ciliation frequency was observed specifically in neurons differentiated from CS patient iPSCs","explanation":"The measurement, in cells from patients with the disease this entry describes."}],"notes":null},{"name":"Cilium length in patient fibroblasts and neural progenitors","description":null,"target":"Impaired Ciliary Protein Trafficking","direction":"DECREASED","interpretation":"In the non-neuronal patient cells the defect is a shorter cilium at a normal ciliation rate, which is a milder and qualitatively different abnormality.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:40825043","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40825043","reference_title":"RAB23 loss-of-function mutation causes context-dependent ciliopathy in Carpenter syndrome.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"the patients' fibroblasts, iPSCs and neural progenitor cells maintained normal ciliation percentages but shortened cilia length","explanation":"The contrasting result in the same patients' other cell types, which is what establishes the dependence on cell type rather than on genotype."}],"notes":null}],"evidence":[{"reference":"PMID:40825043","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40825043","reference_title":"RAB23 loss-of-function mutation causes context-dependent ciliopathy in Carpenter syndrome.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Through the use of patient-derived iPSCs differentiated cells, we present direct evidence of primary cilia anomalies in CS, thereby confirming CS as a ciliopathy disorder.","explanation":"The authors' statement of what this system establishes: that the ciliary defect is present in human patient cells and not only in animal models."},{"reference":"PMID:40825043","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40825043","reference_title":"RAB23 loss-of-function mutation causes context-dependent ciliopathy in Carpenter syndrome.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"A profound reduction in ciliation frequency was observed specifically in neurons differentiated from CS patient iPSCs","explanation":"The measurement, in cells from patients with the disease this entry describes."},{"reference":"PMID:40825043","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40825043","reference_title":"RAB23 loss-of-function mutation causes context-dependent ciliopathy in Carpenter syndrome.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"the patients' fibroblasts, iPSCs and neural progenitor cells maintained normal ciliation percentages but shortened cilia length","explanation":"The contrasting result in the same patients' other cell types, which is what establishes the dependence on cell type rather than on genotype."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:RAB23-Related_Carpenter_Syndrome","model_node_id":"model:kb/disorders/RAB23-Related_Carpenter_Syndrome.yaml:Carpenter syndrome patient-derived iPSC neural lineage","focus_node_id":"node:disorder%3ARAB23-Related_Carpenter_Syndrome:pathophysiology:Impaired%20Ciliary%20Protein%20Trafficking","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/RAB23-related_Carpenter_Syndrome.html#pathograph","nodes":[{"id":"model:kb/disorders/RAB23-Related_Carpenter_Syndrome.yaml:Carpenter syndrome patient-derived iPSC neural lineage","kind":"experimental_model","kind_label":"NAM model","label":"Carpenter syndrome patient-derived iPSC neural lineage","description":"Induced pluripotent stem cells from Carpenter syndrome patients, differentiated down the neural lineage. 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A study that had sampled fibroblasts alone would have concluded the ciliary defect was mild.","url":"https://dismech.monarchinitiative.org/pages/disorders/RAB23-related_Carpenter_Syndrome.html#experimental-model-carpenter-syndrome-patient-derived-ipsc-neural-lineage","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ARAB23-Related_Carpenter_Syndrome:pathophysiology:Impaired%20Ciliary%20Protein%20Trafficking","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Ciliary Protein Trafficking","description":"RAB23 participates in protein delivery to the primary cilium, the organelle in which vertebrate Hedgehog signal transduction is organised. This places Carpenter syndrome adjacent to the ciliopathies, which it partly resembles clinically, though RAB23 also has functions independent of cilia and of Hedgehog.\nTwo ciliary cargoes have been identified, and the specificity of the first is the informative part. Depleting RAB23 lowers the ciliary steady-state level of Smoothened - the Hedgehog transducer - while leaving the control proteins EB1 and Kim1 untouched, so this is not a general collapse of ciliary import but a defect in turnover of a particular cargo. The second is Kif17, a kinesin-2 motor: RAB23 sits in a complex with Kif17 and importin beta-2, and Kif17 fails to reach the cilium in RAB23-depleted cells.\nWhether the cilium is affected at all depends on the cell type. Across a conditional knockout mouse, patient-derived iPSCs and zebrafish morphants, ciliary defects appear in chondrocytes, fibroblasts, neural progenitors and neocortical neurons but not in epithelial cells, cerebellar granule cells or hippocampal neurons - and the defect itself differs, being reduced ciliation frequency in patient-derived neurons but merely shortened cilia in the same patients' fibroblasts and progenitors. That cell-type dependence is a candidate explanation for why a lesion in a ubiquitous trafficking GTPase produces a phenotype concentrated in skull and limb.","url":"https://dismech.monarchinitiative.org/pages/disorders/RAB23-related_Carpenter_Syndrome.html#pathophysiology-impaired-ciliary-protein-trafficking","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ARAB23-Related_Carpenter_Syndrome:pathophysiology:Hedgehog%20Signalling%20Dysregulation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Hedgehog Signalling Dysregulation","description":"RAB23 antagonises Sonic hedgehog signalling, so its loss releases the pathway from negative regulation. This was the first mechanism proposed for Carpenter syndrome and was itself surprising, because craniosynostosis is not typically caused by variants in other Hedgehog pathway components. Mouse work later showed that the Hedgehog change in the suture is one arm of a broader signalling imbalance rather than the whole story.\nThe classical genetics says de-repression, and the cell biology does not straightforwardly agree. Two results point the other way: depleting RAB23 lowers ciliary Smoothened, and RAB23-knockout neural progenitors are desensitized to cilium-dependent Hedgehog activation. Smoothened is the pathway's transducer, so less of it in the cilium and a blunted response to ligand are reduced output, not release from repression. This node is named for the dysregulation rather than for a direction because of that: an earlier name asserting de-repression would have contradicted the node's own modifier.\nThe proposed reconciliation is that RAB23 does two separable things. It represses basal pathway activity, and it also facilitates activation by ligand through the cilium. Both were measured in one cell population: Rab23-depleted cerebellar granule cell precursors have a raised basal Shh signal and a blunted response to Shh ligand and to a Smoothened agonist. Losing RAB23 therefore raises the floor and lowers the ceiling, and the classical genetics and the trafficking work are each reporting one of those.\nThis is why the pathway modifier is DYSREGULATED rather than INCREASED. On the dual-function reading that is not a refusal to commit but the accurate description: the pathway is deranged in two directions at once, and which one dominates in the cranial suture has not been measured.","url":"https://dismech.monarchinitiative.org/pages/disorders/RAB23-related_Carpenter_Syndrome.html#pathophysiology-hedgehog-signalling-dysregulation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ARAB23-Related_Carpenter_Syndrome:pathophysiology:RAB23%20Loss%20of%20Function","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"RAB23 Loss of Function","description":"Biallelic RAB23 variants abolish or impair a small GTPase that cycles between GDP-bound inactive and GTP-bound active states. The reported allele spectrum is dominated by truncating changes, with a recurrent founder nonsense allele; the point mutations that have been characterised structurally fall within the GTPase domain, and the Y79 deletion distorts the switch II region, which is the surface through which an activated Rab engages its effectors. The consequence is loss of function rather than a gain or a change of specificity.\nThree molecular routes to that loss have been demonstrated, and they are not variations on one theme. Most truncating alleles never make a protein at all: their transcripts are degraded by nonsense-mediated decay, shown experimentally rather than inferred from the premature stop codon. A frameshift late enough to escape that fate reaches the same endpoint differently, by deleting the C-terminal prenylatable cysteine, so a protein is made but cannot be lipid-anchored to the membranes it must work on. The missense and in-frame alleles leave a full-length, membrane-competent protein whose effector surface is distorted. All three converge on absent RAB23 activity, which is why the entry treats the allele spectrum as functionally uniform despite its structural variety - and is consistent with the absence of any reported genotype-phenotype correlation.","url":"https://dismech.monarchinitiative.org/pages/disorders/RAB23-related_Carpenter_Syndrome.html#pathophysiology-rab23-loss-of-function","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/RAB23-Related_Carpenter_Syndrome.yaml:Carpenter syndrome patient-derived iPSC neural lineage","source_id":"model:kb/disorders/RAB23-Related_Carpenter_Syndrome.yaml:Carpenter syndrome patient-derived iPSC neural 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What is well supported is that exposure alone is insufficient, since only a minority of people living in identical conditions develop the disease.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Endomyocardial_Fibrosis.html#pathophysiology-chronic-antigenic-or-toxic-stimulus-in-a-susceptible-host","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEndomyocardial_Fibrosis:pathophysiology:Sustained%20eosinophilia%20and%20Th2-skewed%20immune%20activation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Sustained eosinophilia and Th2-skewed immune activation","description":"Persistent eosinophilia is the pivot of the accepted model. 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That asymmetry is real and is curated as such rather than smoothed over.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Endomyocardial_Fibrosis.html#pathophysiology-sustained-eosinophilia-and-th2-skewed-immune-activation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Endomyocardial_Fibrosis.yaml:Cassava-fed Cercopithecus aethiops with protein deprivation","source_id":"model:kb/disorders/Endomyocardial_Fibrosis.yaml:Cassava-fed Cercopithecus aethiops with protein deprivation","target_id":"node:disorder%3AEndomyocardial_Fibrosis:pathophysiology:Chronic%20antigenic%20or%20toxic%20stimulus%20in%20a%20susceptible%20host","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Not Specified","directed":false,"relationship":"NOT_SPECIFIED","fidelity":"NOT_SPECIFIED","causal_link_type":null,"causal_link_type_label":null,"description":"The model instantiates the proposed dietary toxic exposure directly.\n","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3AEndomyocardial_Fibrosis:0:0","source_id":"node:disorder%3AEndomyocardial_Fibrosis:pathophysiology:Chronic%20antigenic%20or%20toxic%20stimulus%20in%20a%20susceptible%20host","target_id":"node:disorder%3AEndomyocardial_Fibrosis:pathophysiology:Sustained%20eosinophilia%20and%20Th2-skewed%20immune%20activation","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[0]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"A chronic antigenic stimulus in a susceptible host is proposed to drive persistent eosinophilia, which is the first step of the mechanistic model.\n","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1}]}},{"target":"Dense endocardial fibrous scar","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Endomyocardial_Fibrosis.html#pathophysiology-dense-endocardial-fibrous-scar","relationship":"NOT_SPECIFIED","relationship_label":"Not Specified","fidelity":"NOT_SPECIFIED","fidelity_label":"Not Specified","description":"The model reproduces the defining endocardial lesion, including its apical and papillary distribution.\n","limitations":null,"biological_scale":"TISSUE","anatomy":[{"id":"UBERON:0002165","label":"endocardium","display_label":"Endocardium","url":"http://purl.obolibrary.org/obo/UBERON_0002165"}],"cell_types":[],"biological_processes":[{"id":"GO:0030198","label":"extracellular matrix organization","display_label":"extracellular matrix organization","url":"http://purl.obolibrary.org/obo/GO_0030198"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[],"evidence":[],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Endomyocardial_Fibrosis","model_node_id":"model:kb/disorders/Endomyocardial_Fibrosis.yaml:Cassava-fed Cercopithecus aethiops with protein deprivation","focus_node_id":"node:disorder%3AEndomyocardial_Fibrosis:pathophysiology:Dense%20endocardial%20fibrous%20scar","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Endomyocardial_Fibrosis.html#pathograph","nodes":[{"id":"model:kb/disorders/Endomyocardial_Fibrosis.yaml:Cassava-fed Cercopithecus aethiops with protein deprivation","kind":"experimental_model","kind_label":"NAM model","label":"Cassava-fed Cercopithecus aethiops with protein deprivation","description":"The only animal model that reproduces the human lesion from a proposed natural exposure rather than from a laboratory insult. 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distinguishes a cassava-specific effect from protein deprivation alone, and the single most informative result in the model."}],"evidence_text":["By the 160th day, the former exhibited marked thickening of the endocardium, interstitial fibrosis, fibrous septa formation, pappillary muscle fibrosis as well as apical fibrosis of the left ventricle, which findings occur in the human disease.","the animals on bananas, which also lacked protein did not develop similar changes","Documents recapitulation of the specific human lesion, including its apical and papillary distribution.","The control that distinguishes a cassava-specific effect from protein deprivation alone, and the single most informative result in the model."],"evidence_status":"Evidence recorded","metadata_completeness":60,"metadata_present":["Model category","Organism","Anatomy","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Cell type","Cell source","Culture system"],"dataset_context":"None 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These model findings do not establish global absence of T-cell activation in patients; PHA and anti-CD3/CD28 responses can be preserved in particular patients or assay conditions.","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_immunodeficiency_due_to_CD3gamma_deficiency.html#pathophysiology-attenuated-t-cell-receptor-signaling","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACombined_Immunodeficiency_Due_To_CD3gamma_Deficiency:pathophysiology:Distorted%20Thymic%20Selection%20and%20Self-Reactive%20Repertoire","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Distorted Thymic Selection and Self-Reactive Repertoire","description":"Reduced TCR signaling is proposed to alter thymic selection and the fate of self-reactive CD4 cells. 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The 2026 count of 11/11 abnormal responses to at least one mitogen does not establish universal impairment of PHA-induced transformation or predict clinical severity.","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_immunodeficiency_due_to_CD3gamma_deficiency.html#pathophysiology-impaired-t-cell-proliferative-response","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACombined_Immunodeficiency_Due_To_CD3gamma_Deficiency:pathophysiology:Impaired%20TCR%2FCD3%20Complex%20Assembly%20and%20Surface%20Expression","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired TCR/CD3 Complex Assembly and Surface Expression","description":"CD3gamma deficiency lowers, without invariably abolishing, surface TCR/CD3 expression in human T cells. 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Human gamma-delta receptors can incorporate CD3delta, providing a supported explanation for partial compensation in that lineage.","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_immunodeficiency_due_to_CD3gamma_deficiency.html#pathophysiology-impaired-tcr-cd3-complex-assembly-and-surface-expression","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACombined_Immunodeficiency_Due_To_CD3gamma_Deficiency:pathophysiology:Reduced%20Thymic%20Output%20and%20Altered%20T-Cell%20Homeostasis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced Thymic Output and Altered T-Cell Homeostasis","description":"Human CD3G case studies infer reduced thymic output from low TRECs and naive-cell numbers despite preservation or later accumulation of peripheral polyclonal memory T cells. 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The highest levels of aberrant splicing and cilia defects were observed in optic cups, explaining the retinal-specific manifestation of this CEP290 mutation.","explanation":"Cilia defects tracking aberrant CEP290 splicing in photoreceptor-containing optic cups is the node's lesion in a human model."},{"reference":"PMID:27151457","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/27151457","reference_title":"Identification and Correction of Mechanisms Underlying Inherited Blindness in Human iPSC-Derived Optic Cups.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The highest levels of aberrant splicing and cilia defects were observed in optic cups","explanation":"Reports the splicing measurement."},{"reference":"PMID:27151457","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/27151457","reference_title":"Identification and Correction of Mechanisms Underlying Inherited Blindness in Human iPSC-Derived Optic Cups.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Treating optic cups with an antisense morpholino effectively blocked aberrant splicing and restored expression of full-length CEP290","explanation":"Reports the antisense rescue measurement."},{"reference":"PMID:27151457","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/27151457","reference_title":"Identification and Correction of Mechanisms Underlying Inherited Blindness in Human iPSC-Derived Optic Cups.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Treating optic cups with an antisense morpholino effectively blocked aberrant splicing and restored expression of full-length CEP290, restoring normal cilia-based protein trafficking.","explanation":"Restoration of normal trafficking implies it was abnormal in untreated mutant cups; the inference runs through the rescue."},{"reference":"PMID:27151457","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/27151457","reference_title":"Identification and Correction of Mechanisms Underlying Inherited Blindness in Human iPSC-Derived Optic Cups.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"restoring normal cilia-based protein trafficking","explanation":"Reports the trafficking measurement in the rescue arm."}],"evidence_text":["we generated differentiated photoreceptors in three-dimensional optic cups and retinal pigment epithelium (RPE) from iPSCs with this common CEP290 mutation to investigate disease mechanisms and evaluate candidate therapies.","iPSCs differentiated normally into RPE and optic cups, despite abnormal CEP290 splicing and cilia defects. The highest levels of aberrant splicing and cilia defects were observed in optic cups, explaining the retinal-specific manifestation of this CEP290 mutation.","The highest levels of aberrant splicing and cilia defects were observed in optic cups","Treating optic cups with an antisense morpholino effectively blocked aberrant splicing and restored expression of full-length CEP290","Treating optic cups with an antisense morpholino effectively blocked aberrant splicing and restored expression of full-length CEP290, restoring normal cilia-based protein trafficking.","restoring normal cilia-based protein trafficking","Establishes the patient optic-cup model.","Cilia defects tracking aberrant CEP290 splicing in photoreceptor-containing optic cups is the node's lesion in a human model.","Reports the splicing measurement.","Reports the antisense rescue measurement.","Restoration of normal trafficking implies it was abnormal in untreated mutant cups; the inference runs through the 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The zebrafish knockout adds a candidate effector, upregulated canonical Wnt/beta-catenin signalling, which is pharmacologically reversible in that model; it is recorded here as a model-organism lead rather than an established human mechanism.","url":"https://dismech.monarchinitiative.org/pages/disorders/Cartilage-hair_hypoplasia.html#pathophysiology-growth-plate-chondrocyte-differentiation-failure","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACartilage-Hair_Hypoplasia:pathophysiology:Hair%20Follicle%20Hypoplasia","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Hair Follicle Hypoplasia","description":"Hair hypoplasia gives the disease the second half of its name and is one of the phenotypes that tracks the messenger-RNA cleavage arm rather than the ribosomal one. 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defects in Lec5 and Lec9 Chinese hamster ovary cells.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"N-glycan synthesis and changes in polyisoprenoid levels were corrected by complementation with human DHRSX but not with SRD5A3","explanation":"Reports the discriminating complementation result."}],"notes":null}],"evidence":[{"reference":"PMID:39395802","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39395802","reference_title":"Absence of the dolichol synthesis gene DHRSX leads to N-glycosylation defects in Lec5 and Lec9 Chinese hamster ovary cells.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Long-read whole genome sequencing of Lec5 and Lec9 cells did not reveal mutations in the ORF of SRD5A3, but the genomic region containing DHRSX was absent.","explanation":"Establishes that these long-studied mutants are DHRSX-deficient, making them a valid model of the human lesion."},{"reference":"PMID:39395802","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39395802","reference_title":"Absence of the dolichol synthesis gene DHRSX leads to N-glycosylation defects in Lec5 and Lec9 Chinese hamster ovary cells.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"the typical polyprenol dehydrogenase and dolichal reductase activities of DHRSX were absent in membrane preparations derived from Lec5 and Lec9 cells, while the reduction of polyprenal to dolichal, catalyzed by SRD5A3, was unaffected","explanation":"Reports the enzyme activity measurements distinguishing the DHRSX steps from the SRD5A3 step."},{"reference":"PMID:39395802","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39395802","reference_title":"Absence of the dolichol synthesis gene DHRSX leads to N-glycosylation defects in Lec5 and Lec9 Chinese hamster ovary cells.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"N-glycan synthesis and changes in polyisoprenoid levels were corrected by complementation with human DHRSX but not with SRD5A3","explanation":"Reports the discriminating complementation result."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:DHRSX-Congenital_Disorder_of_Glycosylation","model_node_id":"model:kb/disorders/DHRSX-Congenital_Disorder_of_Glycosylation.yaml:CHO Lec5 and Lec9 glycosylation mutants","focus_node_id":"node:disorder%3ADHRSX-Congenital_Disorder_of_Glycosylation:pathophysiology:Impaired%20Dolichol%20Synthesis%20from%20Polyprenol","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/DHRSX-Congenital_Disorder_of_Glycosylation.html#pathograph","nodes":[{"id":"model:kb/disorders/DHRSX-Congenital_Disorder_of_Glycosylation.yaml:CHO Lec5 and Lec9 glycosylation mutants","kind":"experimental_model","kind_label":"NAM model","label":"CHO Lec5 and Lec9 glycosylation mutants","description":"Chinese hamster ovary lectin-resistance mutants isolated decades ago with a known but unexplained block in polyprenol-to-dolichol conversion. Once DHRSX was described, both were shown to lack the DHRSX genomic region, closing a long-standing gap. They are a natural-experiment model of complete DHRSX deficiency, and their pre-existing characterization independently corroborates the pathway.","url":"https://dismech.monarchinitiative.org/pages/disorders/DHRSX-Congenital_Disorder_of_Glycosylation.html#experimental-model-cho-lec5-and-lec9-glycosylation-mutants","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ADHRSX-Congenital_Disorder_of_Glycosylation:pathophysiology:Impaired%20Dolichol%20Synthesis%20from%20Polyprenol","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Dolichol Synthesis from Polyprenol","description":"Cells lacking DHRSX accumulate polyprenol and its phosphorylated and hexosylated derivatives while dolichol and its derivatives fall — that is, the polyprenol-to-dolichol ratio rises. Polyprenal levels are unchanged, which is the observation that localizes the block to the DHRSX steps rather than the SRD5A3 step.","url":"https://dismech.monarchinitiative.org/pages/disorders/DHRSX-Congenital_Disorder_of_Glycosylation.html#pathophysiology-impaired-dolichol-synthesis-from-polyprenol","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ADHRSX-Congenital_Disorder_of_Glycosylation:pathophysiology:Defective%20Lipid-Linked%20Oligosaccharide%20Maturation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Defective Lipid-Linked Oligosaccharide Maturation","description":"Dolichol-phosphate is rate-limiting for N-glycosylation because dolichol-phosphate sugars are used at seven steps of LLO assembly. DPAGT1 (which transfers GlcNAc-1-P onto Dol-P), DPM synthase, and ALG3 (which adds the sixth mannose) are all markedly inefficient when handed the polyprenol-linked analogue instead. The LLO therefore stalls as an immature linear Man-5 species, with Man-4 arising downstream through EDEM3.","url":"https://dismech.monarchinitiative.org/pages/disorders/DHRSX-Congenital_Disorder_of_Glycosylation.html#pathophysiology-defective-lipid-linked-oligosaccharide-maturation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ADHRSX-Congenital_Disorder_of_Glycosylation:pathophysiology:DHRSX%20Oxidoreductase%20Deficiency","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"DHRSX Oxidoreductase Deficiency","description":"The reported variants — p.(Thr49Met), p.(Val181Phe), and p.(Leu215Phe) — cluster around the predicted NAD(P)+ binding site and the substrate access channel. Thr49 is an obligatory residue of the Class IV NAD(P)+ binding motif; Val181 contacts the cofactor directly and sits at the mouth of the substrate channel; Leu215 lies along that channel. All three are therefore expected to impair the enzyme's oxidoreductase function. They also destabilize the protein: patient cells carry about 4-5% of control DHRSX protein while mRNA remains at 34-68% of control, so the dominant effect is loss of the enzyme rather than a purely catalytic lesion in a normally abundant one.","url":"https://dismech.monarchinitiative.org/pages/disorders/DHRSX-Congenital_Disorder_of_Glycosylation.html#pathophysiology-dhrsx-oxidoreductase-deficiency","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/DHRSX-Congenital_Disorder_of_Glycosylation.yaml:CHO Lec5 and Lec9 glycosylation mutants","source_id":"model:kb/disorders/DHRSX-Congenital_Disorder_of_Glycosylation.yaml:CHO Lec5 and Lec9 glycosylation mutants","target_id":"node:disorder%3ADHRSX-Congenital_Disorder_of_Glycosylation:pathophysiology:Impaired%20Dolichol%20Synthesis%20from%20Polyprenol","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"HIGH","causal_link_type":null,"causal_link_type_label":null,"description":"Both lines show the DHRSX-deficiency polyisoprenoid signature and loss of the two DHRSX enzymatic activities with SRD5A3 activity intact, and both are corrected by human DHRSX but not by SRD5A3.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ADHRSX-Congenital_Disorder_of_Glycosylation:0:0","source_id":"node:disorder%3ADHRSX-Congenital_Disorder_of_Glycosylation:pathophysiology:DHRSX%20Oxidoreductase%20Deficiency","target_id":"node:disorder%3ADHRSX-Congenital_Disorder_of_Glycosylation:pathophysiology:Impaired%20Dolichol%20Synthesis%20from%20Polyprenol","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"DHRSX catalyses two of the three steps converting polyprenol to dolichol, so loss of its oxidoreductase activity blocks the pathway at both ends.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ADHRSX-Congenital_Disorder_of_Glycosylation:1:0","source_id":"node:disorder%3ADHRSX-Congenital_Disorder_of_Glycosylation:pathophysiology:Impaired%20Dolichol%20Synthesis%20from%20Polyprenol","target_id":"node:disorder%3ADHRSX-Congenital_Disorder_of_Glycosylation:pathophysiology:Defective%20Lipid-Linked%20Oligosaccharide%20Maturation","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Dolichol-phosphate availability is rate-limiting for N-glycosylation, and polyprenol-phosphate substitutes poorly for it at several LLO assembly steps.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1}]}}],"mechanism_names":["Impaired Dolichol Synthesis from Polyprenol"],"relationships":["Recapitulates"],"fidelities":["High"],"biological_scales":["Molecular"],"system_context_sources":["Linked mechanism biological scale"],"modeled_system_labels":["Molecular"],"biological_process_terms":[],"biological_processes":[],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[{"id":"CHEBI:26199","label":"polyprenol","display_label":"polyprenol","url":"http://purl.obolibrary.org/obo/CHEBI_26199"},{"id":"CHEBI:16091","label":"dolichol","display_label":"dolichol","url":"http://purl.obolibrary.org/obo/CHEBI_16091"}],"chemicals":["polyprenol","dolichol"],"readout_names":["Polyprenol dehydrogenase and dolichal reductase activity in membranes","N-glycan synthesis after DHRSX versus SRD5A3 complementation"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:39395802","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39395802","reference_title":"Absence of the dolichol synthesis gene DHRSX leads to N-glycosylation defects in Lec5 and Lec9 Chinese hamster ovary cells.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Long-read whole genome sequencing of Lec5 and Lec9 cells did not reveal mutations in the ORF of SRD5A3, but the genomic region containing DHRSX was absent.","explanation":"Establishes that these long-studied mutants are DHRSX-deficient, making them a valid model of the human lesion."},{"reference":"PMID:39395802","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39395802","reference_title":"Absence of the dolichol synthesis gene DHRSX leads to N-glycosylation defects in Lec5 and Lec9 Chinese hamster ovary cells.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"the typical polyprenol dehydrogenase and dolichal reductase activities of DHRSX were absent in membrane preparations derived from Lec5 and Lec9 cells, while the reduction of polyprenal to dolichal, catalyzed by SRD5A3, was unaffected","explanation":"Reports the enzyme activity measurements distinguishing the DHRSX steps from the SRD5A3 step."},{"reference":"PMID:39395802","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39395802","reference_title":"Absence of the dolichol synthesis gene DHRSX leads to N-glycosylation defects in Lec5 and Lec9 Chinese hamster ovary cells.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"N-glycan synthesis and changes in polyisoprenoid levels were corrected by complementation with human DHRSX but not with SRD5A3","explanation":"Reports the discriminating complementation result."}],"evidence_text":["Long-read whole genome sequencing of Lec5 and Lec9 cells did not reveal mutations in the ORF of SRD5A3, but the genomic region containing DHRSX was absent.","the typical polyprenol dehydrogenase and dolichal reductase activities of DHRSX were absent in membrane preparations derived from Lec5 and Lec9 cells, while the reduction of polyprenal to dolichal, catalyzed by SRD5A3, was unaffected","N-glycan synthesis and changes in polyisoprenoid levels were corrected by complementation with human DHRSX but not with SRD5A3","Establishes that these long-studied mutants are DHRSX-deficient, making them a valid model of the human lesion.","Reports the enzyme activity measurements distinguishing the DHRSX steps from the SRD5A3 step.","Reports the discriminating complementation result."],"evidence_status":"Evidence recorded","metadata_completeness":40,"metadata_present":["Model category","NAMO class","Modeled mechanism","Evidence"],"metadata_missing":["Organism","Anatomy","Cell type","Cell source","Culture system","Publication"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/DHRSX-Congenital_Disorder_of_Glycosylation.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/DHRSX-Congenital_Disorder_of_Glycosylation.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/DHRSX-Congenital_Disorder_of_Glycosylation.html#experimental-model-cho-lec5-and-lec9-glycosylation-mutants","source_anchor":"experimental-model-cho-lec5-and-lec9-glycosylation-mutants"},{"id":"model:kb/disorders/IFAP_Syndrome_1.yaml:CHO M19 site-2-protease-deficient complementation assay","name":"CHO M19 site-2-protease-deficient complementation assay","description":"Chinese hamster ovary M19 cells lack endogenous S2P and therefore cannot grow without exogenous cholesterol and lipid. Transfecting human MBTPS2 rescues them, and patient variants rescue them only partially - read out both by an SRE-regulated reporter and by growth in lipid-free medium.\nThis is the assay the entire pathogenicity classification of MBTPS2 variants rests on, and it is the reason the severity relationship in this disease is quantitative rather than categorical.","notes":null,"context_id":"disorder:IFAP_Syndrome_1","context_kind":"Disorder","disease_name":"IFAP Syndrome 1","disease_synonyms":["IFAP","ichthyosis follicularis, atrichia and photophobia syndrome","ichthyosis follicularis-alopecia-photophobia syndrome","IFAP/BRESHECK syndrome","MBTPS2-related IFAP syndrome"],"disease_term":{"id":"MONDO:0100213","label":"IFAP syndrome 1, with or without BRESHECK syndrome","display_label":"IFAP syndrome","url":"http://purl.obolibrary.org/obo/MONDO_0100213"},"experimental_model_type":"CELL_LINE","experimental_model_type_label":"Cell line","namo_type":"namo:CellLineModel","declared_namo_class_name":null,"namo_class_name":"CellLineModel","namo_class_label":"Cell Line Model","namo_description":"A model system based on immortalized cell lines that can be maintained in culture indefinitely. Examples: HepG2, A549, Caco-2, etc.","namo_docs_url":"https://monarch-initiative.github.io/namo/elements/CellLineModel/","namo_ontology_url":"https://w3id.org/monarch-initiative/namo/CellLineModel","namo_mapping_basis":"Safe mapping from DisMech category","namo_class_in_schema":true,"namo_schema_status":"Defined in NAMO schema used for this build","modality":"Cellular system","organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[{"id":"CL:0000312","label":"keratinocyte","display_label":"keratinocyte","url":"http://purl.obolibrary.org/obo/CL_0000312"}],"linked_cell_type_labels":["keratinocyte"],"cell_types":[{"id":"CL:0000312","label":"keratinocyte","display_label":"keratinocyte","url":"http://purl.obolibrary.org/obo/CL_0000312"}],"cell_type_labels":["keratinocyte"],"conditions":[],"cell_source":null,"source_category":"Immortalized / cell line","culture_system":null,"publication":null,"publication_url":null,"mechanisms":[{"target":"Impaired SREBP-Driven Lipid Synthesis","target_url":"https://dismech.monarchinitiative.org/pages/disorders/IFAP_Syndrome_1.html#pathophysiology-impaired-srebp-driven-lipid-synthesis","relationship":"MEASURES","relationship_label":"Measures","fidelity":"MODERATE","fidelity_label":"Moderate","description":"Quantifies residual S2P activity through its SREBP output, which is what makes the activity-severity correlation measurable.\nCurated as MEASURES rather than RECAPITULATES on purpose: the cell line does not model IFAP, it assays one function of the mutant protein. Nothing about a hamster ovary cell reproduces a hair follicle or a corneal limbus.","limitations":"Two limits worth stating. The readout is the SREBP arm; the assay in its original form says nothing about ATF6, which is why the ER-stress node is graded lower. And a rodent ovary-derived line carries none of the tissue-specific context that determines why the phenotype falls on skin, hair and cornea rather than on the many other tissues that need SREBP.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[{"id":"CL:0000312","label":"keratinocyte","display_label":"keratinocyte","url":"http://purl.obolibrary.org/obo/CL_0000312"}],"biological_processes":[{"id":"GO:0032933","label":"SREBP signaling pathway","display_label":"SREBP signaling pathway","url":"http://purl.obolibrary.org/obo/GO_0032933"},{"id":"GO:0006695","label":"cholesterol biosynthetic process","display_label":"cholesterol biosynthesis","url":"http://purl.obolibrary.org/obo/GO_0006695"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"SRE-regulated reporter induction and growth in lipid-free medium","description":null,"target":"Impaired SREBP-Driven Lipid Synthesis","direction":"DECREASED","interpretation":"Patient variants complement the M19 deficiency less well than wild-type MBTPS2, and the shortfall is graded rather than all-or-none.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:19361614","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/19361614","reference_title":"IFAP syndrome is caused by deficiency in MBTPS2, an intramembrane zinc metalloprotease essential for cholesterol homeostasis and ER stress response.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Wild-type MBTPS2 was able to complement the protease deficiency in Chinese hamster M19 cells as shown by induction of an SRE-regulated reporter gene in transient transfection experiments and by growth of stably transfected cells in media devoid of cholesterol and lipids.","explanation":"The two readouts of the assay, in the paper that established it for this gene."}],"notes":null}],"evidence":[{"reference":"PMID:19361614","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/19361614","reference_title":"IFAP syndrome is caused by deficiency in MBTPS2, an intramembrane zinc metalloprotease essential for cholesterol homeostasis and ER stress response.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The degree of diminished activity correlated with clinical severity as noted in male patients.","explanation":"Supports treating this assay as informative for the disease: its output tracks the clinical phenotype."},{"reference":"PMID:19361614","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/19361614","reference_title":"IFAP syndrome is caused by deficiency in MBTPS2, an intramembrane zinc metalloprotease essential for cholesterol homeostasis and ER stress response.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Wild-type MBTPS2 was able to complement the protease deficiency in Chinese hamster M19 cells as shown by induction of an SRE-regulated reporter gene in transient transfection experiments and by growth of stably transfected cells in media devoid of cholesterol and lipids.","explanation":"The two readouts of the assay, in the paper that established it for this gene."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:IFAP_Syndrome_1","model_node_id":"model:kb/disorders/IFAP_Syndrome_1.yaml:CHO M19 site-2-protease-deficient complementation assay","focus_node_id":"node:disorder%3AIFAP_Syndrome_1:pathophysiology:Impaired%20SREBP-Driven%20Lipid%20Synthesis","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/IFAP_Syndrome_1.html#pathograph","nodes":[{"id":"model:kb/disorders/IFAP_Syndrome_1.yaml:CHO M19 site-2-protease-deficient complementation assay","kind":"experimental_model","kind_label":"NAM model","label":"CHO M19 site-2-protease-deficient complementation assay","description":"Chinese hamster ovary M19 cells lack endogenous S2P and therefore cannot grow without exogenous cholesterol and lipid. Transfecting human MBTPS2 rescues them, and patient variants rescue them only partially - read out both by an SRE-regulated reporter and by growth in lipid-free medium.\nThis is the assay the entire pathogenicity classification of MBTPS2 variants rests on, and it is the reason the severity relationship in this disease is quantitative rather than categorical.","url":"https://dismech.monarchinitiative.org/pages/disorders/IFAP_Syndrome_1.html#experimental-model-cho-m19-site-2-protease-deficient-complementation-assay","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AIFAP_Syndrome_1:pathophysiology:Impaired%20SREBP-Driven%20Lipid%20Synthesis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired SREBP-Driven Lipid Synthesis","description":"Less active SREBP reaches the nucleus, so cholesterol and fatty-acid synthesis genes are under-induced. The functional signature of this in the assays used to prove variant pathogenicity is failure to grow in cholesterol-depleted medium - a cell that cannot make its own lipid and is no longer given any.\nIn the epidermis this is the barrier-lipid arm: the cornified envelope depends on locally synthesised lipids, and a follicular hyperkeratosis is what a failing keratinisation programme looks like at the skin surface.","url":"https://dismech.monarchinitiative.org/pages/disorders/IFAP_Syndrome_1.html#pathophysiology-impaired-srebp-driven-lipid-synthesis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3AIFAP_Syndrome_1:pathophysiology:Defective%20Epidermal%20and%20Follicular%20Keratinization","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Defective Epidermal and Follicular Keratinization","description":"The skin and hair phenotype: spiny follicular hyperkeratosis and near-total absence of scalp hair, eyebrows and eyelashes from birth.\nGraded PROVISIONAL because the step from an impaired lipid-synthesis programme to this specific histology is inferred, not demonstrated. No study reviewed here measures barrier lipids, cornified envelope composition or follicular differentiation markers in IFAP skin. The disease is defined clinically at this level and mechanistically two levels up, with the connection assumed.","url":"https://dismech.monarchinitiative.org/pages/disorders/IFAP_Syndrome_1.html#pathophysiology-defective-epidermal-and-follicular-keratinization","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3AIFAP_Syndrome_1:pathophysiology:Progressive%20Vascularising%20Keratopathy","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Progressive Vascularising Keratopathy","description":"The ocular phenotype, and the one that carries the morbidity. Photophobia is the symptom; the disease is a keratopathy that progresses through spontaneous epithelial defects, superficial and deep corneal vascularisation, and scarring to counting-fingers acuity.\nThe most informative observation is developmental rather than static. An infant diagnosed at six days had clear corneas; the epithelial defects appeared at six months, and imaging then showed limbal thickening, peripheral pannus, conjunctivalisation and abnormal hyperreflective epithelium - the picture of limbal stem cell dysfunction. So the cornea is not malformed, it fails to maintain itself, which is a different therapeutic target.\nGraded PROVISIONAL: the limbal-failure account rests on one prospectively followed infant, and no histology or limbal-marker study has been published.","url":"https://dismech.monarchinitiative.org/pages/disorders/IFAP_Syndrome_1.html#pathophysiology-progressive-vascularising-keratopathy","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3AIFAP_Syndrome_1:pathophysiology:Reduced%20Regulated%20Intramembrane%20Proteolysis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced Regulated Intramembrane Proteolysis","description":"S2P makes the second cut of a two-cut cascade. SREBP and ATF6 are cleaved first by site-1 protease and then, within the membrane, by S2P, which releases the active transcription-factor domain into the cytosol. Reduce S2P activity and both substrates are released less efficiently.\nThis node is the reason the disease looks pleiotropic. Two entirely unrelated transcriptional programmes share one protease, so a single hypomorphic allele hits lipid synthesis and the stress response together rather than choosing one.","url":"https://dismech.monarchinitiative.org/pages/disorders/IFAP_Syndrome_1.html#pathophysiology-reduced-regulated-intramembrane-proteolysis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"}],"edges":[{"id":"model-link:0:model:kb/disorders/IFAP_Syndrome_1.yaml:CHO M19 site-2-protease-deficient complementation assay","source_id":"model:kb/disorders/IFAP_Syndrome_1.yaml:CHO M19 site-2-protease-deficient complementation assay","target_id":"node:disorder%3AIFAP_Syndrome_1:pathophysiology:Impaired%20SREBP-Driven%20Lipid%20Synthesis","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Measures","directed":false,"relationship":"MEASURES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"Quantifies residual S2P activity through its SREBP output, which is what makes the activity-severity correlation measurable.\nCurated as MEASURES rather than RECAPITULATES on purpose: the cell line does not model IFAP, it assays one function of the mutant protein. Nothing about a hamster ovary cell reproduces a hair follicle or a corneal limbus.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AIFAP_Syndrome_1:2:0","source_id":"node:disorder%3AIFAP_Syndrome_1:pathophysiology:Impaired%20SREBP-Driven%20Lipid%20Synthesis","target_id":"node:disorder%3AIFAP_Syndrome_1:pathophysiology:Defective%20Epidermal%20and%20Follicular%20Keratinization","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[0]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown 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in MBTPS2, an intramembrane zinc metalloprotease essential for cholesterol homeostasis and ER stress response.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The degree of diminished activity correlated with clinical severity as noted in male patients.","explanation":"Supports treating this assay as informative for the disease: its output tracks the clinical phenotype."},{"reference":"PMID:19361614","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/19361614","reference_title":"IFAP syndrome is caused by deficiency in MBTPS2, an intramembrane zinc metalloprotease essential for cholesterol homeostasis and ER stress response.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Wild-type MBTPS2 was able to complement the protease deficiency in Chinese hamster M19 cells as shown by induction of an SRE-regulated reporter gene in transient transfection experiments and by growth of stably transfected cells in media devoid of cholesterol and lipids.","explanation":"The two readouts of the assay, in the paper that established it for this gene."}],"evidence_text":["The degree of diminished activity correlated with clinical severity as noted in male patients.","Wild-type MBTPS2 was able to complement the protease deficiency in Chinese hamster M19 cells as shown by induction of an SRE-regulated reporter gene in transient transfection experiments and by growth of stably transfected cells in media devoid of cholesterol and lipids.","Supports treating this assay as informative for the disease: its output tracks the clinical phenotype.","The two readouts of the assay, in the paper that established it for this gene."],"evidence_status":"Evidence recorded","metadata_completeness":50,"metadata_present":["Model category","NAMO class","Cell type","Modeled mechanism","Evidence"],"metadata_missing":["Organism","Anatomy","Cell source","Culture system","Publication"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/IFAP_Syndrome_1.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/IFAP_Syndrome_1.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/IFAP_Syndrome_1.html#experimental-model-cho-m19-site-2-protease-deficient-complementation-assay","source_anchor":"experimental-model-cho-m19-site-2-protease-deficient-complementation-assay"},{"id":"model:kb/disorders/Peroxisome_Biogenesis_Disorder_12A_Zellweger.yaml:CHO peroxisome-deficient mutant ZP119 (complementation group J)","name":"CHO peroxisome-deficient mutant ZP119 (complementation group J)","description":"A chemically derived Chinese hamster ovary mutant defective in import of both matrix and membrane proteins, later shown to be PEX19-deficient and assigned to the same complementation group as the human CG-J patients. It is the cell line the human PEX19 cDNA was cloned on, by screening a liver cDNA library for restoration of peroxisomes; the sibling mutant ZP165 belongs to the same group. It is a mammalian somatic-cell system rather than an animal model, which is why it sits here and not in `animal_models`.","notes":null,"context_id":"disorder:Peroxisome_Biogenesis_Disorder_12A_Zellweger","context_kind":"Disorder","disease_name":"Peroxisome Biogenesis Disorder 12A (Zellweger)","disease_synonyms":["PBD12A","peroxisome biogenesis disorder, complementation group J","peroxisome biogenesis disorder, complementation group 14","CG-J","PEX19-related Zellweger syndrome"],"disease_term":{"id":"MONDO:0013951","label":"peroxisome biogenesis disorder 12A (Zellweger)","display_label":"peroxisome biogenesis disorder 12A (Zellweger)","url":"http://purl.obolibrary.org/obo/MONDO_0013951"},"experimental_model_type":"CELL_LINE","experimental_model_type_label":"Cell line","namo_type":"namo:CellLineModel","declared_namo_class_name":null,"namo_class_name":"CellLineModel","namo_class_label":"Cell Line Model","namo_description":"A model system based on immortalized cell lines that can be maintained in culture indefinitely. Examples: HepG2, A549, Caco-2, etc.","namo_docs_url":"https://monarch-initiative.github.io/namo/elements/CellLineModel/","namo_ontology_url":"https://w3id.org/monarch-initiative/namo/CellLineModel","namo_mapping_basis":"Safe mapping from DisMech category","namo_class_in_schema":true,"namo_schema_status":"Defined in NAMO schema used for this build","modality":"Cellular system","organism":{"id":"NCBITaxon:10029","label":"Cricetulus griseus","display_label":"Chinese hamster","url":"http://purl.obolibrary.org/obo/NCBITaxon_10029"},"organism_label":"Cricetulus griseus","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":"immortalized rodent cell line","source_category":"Immortalized / cell line","culture_system":"2D monolayer","publication":"PMID:10051604","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/10051604","mechanisms":[{"target":"Absence of Peroxisomal Membrane Compartments","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Peroxisome_Biogenesis_Disorder_12A_Zellweger.html#pathophysiology-absence-of-peroxisomal-membrane-compartments","relationship":"RECAPITULATES","relationship_label":"Recapitulates","fidelity":"MODERATE","fidelity_label":"Moderate","description":"The mutant is devoid of peroxisomal membrane vesicles, which is this node's defining cellular phenotype, and stable expression of human PEX19 restores peroxisome biogenesis - so the line demonstrates the dependency rather than merely displaying it.","limitations":"A rodent somatic-cell mutant, not a patient genotype: it carries whatever lesion the mutagenesis produced rather than a reported human PEX19 allele, and a cultured fibroblast-like cell reports none of the developmental, hepatic or neurological biology that makes this a disease.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0007031","label":"peroxisome organization","display_label":"peroxisome organization","url":"http://purl.obolibrary.org/obo/GO_0007031"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[],"evidence":[{"reference":"PMID:10051604","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/10051604","reference_title":"Human PEX19: cDNA cloning by functional complementation, mutation analysis in a patient with Zellweger syndrome, and potential role in peroxisomal membrane assembly.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"In no CG-J mutant cell were peroxisomal ghosts found","explanation":"The absence of membrane remnants in the group-J cells this line belongs to."},{"reference":"PMID:10051604","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/10051604","reference_title":"Human PEX19: cDNA cloning by functional complementation, mutation analysis in a patient with Zellweger syndrome, and potential role in peroxisomal membrane assembly.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"A stable transformant of ZP119 with HsPEX19 was morphologically and biochemically restored for peroxisome biogenesis.","explanation":"The rescue that makes the phenotype attributable to PEX19 rather than to the line's background."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Peroxisome_Biogenesis_Disorder_12A_Zellweger","model_node_id":"model:kb/disorders/Peroxisome_Biogenesis_Disorder_12A_Zellweger.yaml:CHO peroxisome-deficient mutant ZP119 (complementation group J)","focus_node_id":"node:disorder%3APeroxisome_Biogenesis_Disorder_12A_Zellweger:pathophysiology:Absence%20of%20Peroxisomal%20Membrane%20Compartments","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Peroxisome_Biogenesis_Disorder_12A_Zellweger.html#pathograph","nodes":[{"id":"model:kb/disorders/Peroxisome_Biogenesis_Disorder_12A_Zellweger.yaml:CHO peroxisome-deficient mutant ZP119 (complementation group J)","kind":"experimental_model","kind_label":"NAM model","label":"CHO peroxisome-deficient mutant ZP119 (complementation group J)","description":"A chemically derived Chinese hamster ovary mutant defective in import of both matrix and membrane proteins, later shown to be PEX19-deficient and assigned to the same complementation group as the human CG-J patients. It is the cell line the human PEX19 cDNA was cloned on, by screening a liver cDNA library for restoration of peroxisomes; the sibling mutant ZP165 belongs to the same group. It is a mammalian somatic-cell system rather than an animal model, which is why it sits here and not in `animal_models`.","url":"https://dismech.monarchinitiative.org/pages/disorders/Peroxisome_Biogenesis_Disorder_12A_Zellweger.html#experimental-model-cho-peroxisome-deficient-mutant-zp119-complementation-group-j","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APeroxisome_Biogenesis_Disorder_12A_Zellweger:pathophysiology:Absence%20of%20Peroxisomal%20Membrane%20Compartments","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Absence of Peroxisomal Membrane Compartments","description":"Cells from complementation group J contain no peroxisomal membrane remnants. This is the feature that separates PEX19 disease from the matrix-import peroxisome biogenesis disorders, in which membrane \"ghosts\" persist and can be stained; PEX3 and PEX16 deficiency behave the same way.","url":"https://dismech.monarchinitiative.org/pages/disorders/Peroxisome_Biogenesis_Disorder_12A_Zellweger.html#pathophysiology-absence-of-peroxisomal-membrane-compartments","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APeroxisome_Biogenesis_Disorder_12A_Zellweger:pathophysiology:Collapse%20of%20Peroxisomal%20Matrix%20Protein%20Import","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Collapse of Peroxisomal Matrix Protein Import","description":"With no peroxisomal compartment, matrix enzymes remain in the cytosol, where they are degraded or left in unprocessed precursor form. Expressing wild-type PEX19 in group-J patient fibroblasts restores matrix protein import, which is what demonstrates that the matrix defect is downstream of the PEX19 lesion rather than a separate one.","url":"https://dismech.monarchinitiative.org/pages/disorders/Peroxisome_Biogenesis_Disorder_12A_Zellweger.html#pathophysiology-collapse-of-peroxisomal-matrix-protein-import","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APeroxisome_Biogenesis_Disorder_12A_Zellweger:pathophysiology:Failure%20of%20Cytosolic%20Membrane-Protein%20Targeting","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Failure of Cytosolic Membrane-Protein Targeting","description":"Pex19p is a soluble protein, mostly cytosolic at steady state, that binds a broad range of peroxisomal membrane proteins through the regions those proteins use for peroxisomal targeting, and delivers them to the membrane. Farnesylation of its C-terminal CaaX motif reorganises the cargo-binding surface and strengthens the interaction, which is why alleles truncating that region are inactivating. When Pex19p is absent, newly synthesised membrane proteins are degraded or delivered to mitochondria instead.","url":"https://dismech.monarchinitiative.org/pages/disorders/Peroxisome_Biogenesis_Disorder_12A_Zellweger.html#pathophysiology-failure-of-cytosolic-membrane-protein-targeting","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Peroxisome_Biogenesis_Disorder_12A_Zellweger.yaml:CHO peroxisome-deficient mutant ZP119 (complementation group J)","source_id":"model:kb/disorders/Peroxisome_Biogenesis_Disorder_12A_Zellweger.yaml:CHO peroxisome-deficient mutant ZP119 (complementation group J)","target_id":"node:disorder%3APeroxisome_Biogenesis_Disorder_12A_Zellweger:pathophysiology:Absence%20of%20Peroxisomal%20Membrane%20Compartments","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"The mutant is devoid of peroxisomal membrane vesicles, which is this node's defining cellular phenotype, and stable expression of human PEX19 restores peroxisome biogenesis - so the line demonstrates the dependency rather than merely displaying it.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":2},{"id":"causal:disorder%3APeroxisome_Biogenesis_Disorder_12A_Zellweger:2:0","source_id":"node:disorder%3APeroxisome_Biogenesis_Disorder_12A_Zellweger:pathophysiology:Absence%20of%20Peroxisomal%20Membrane%20Compartments","target_id":"node:disorder%3APeroxisome_Biogenesis_Disorder_12A_Zellweger:pathophysiology:Collapse%20of%20Peroxisomal%20Matrix%20Protein%20Import","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"A matrix cannot be imported into a compartment that does not exist, so matrix import fails as a consequence of the membrane defect rather than in parallel with it.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3APeroxisome_Biogenesis_Disorder_12A_Zellweger:1:0","source_id":"node:disorder%3APeroxisome_Biogenesis_Disorder_12A_Zellweger:pathophysiology:Failure%20of%20Cytosolic%20Membrane-Protein%20Targeting","target_id":"node:disorder%3APeroxisome_Biogenesis_Disorder_12A_Zellweger:pathophysiology:Absence%20of%20Peroxisomal%20Membrane%20Compartments","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"With no route for membrane proteins to reach a peroxisomal membrane, no such membrane is assembled. 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Naming one would assert a mechanism the field has not agreed on; the edge records the dependency and this note records the dispute.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":2}]}},{"target":"Collapse of Peroxisomal Matrix Protein Import","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Peroxisome_Biogenesis_Disorder_12A_Zellweger.html#pathophysiology-collapse-of-peroxisomal-matrix-protein-import","relationship":"RECAPITULATES","relationship_label":"Recapitulates","fidelity":"MODERATE","fidelity_label":"Moderate","description":"The line was isolated as a matrix- and membrane-import double defect, which is the combination this entry's chain predicts: matrix import fails because there is no compartment to import into.","limitations":"Same rodent-somatic-cell caveat. The line cannot separate the two defects in time, so it shows the combination rather than the ordering the edge asserts.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0016558","label":"protein import into peroxisome matrix","display_label":"protein import into peroxisome matrix","url":"http://purl.obolibrary.org/obo/GO_0016558"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[],"evidence":[{"reference":"PMID:10051604","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/10051604","reference_title":"Human PEX19: cDNA cloning by functional complementation, mutation analysis in a patient with Zellweger syndrome, and potential role in peroxisomal membrane assembly.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We have isolated a human PEX19 cDNA (HsPEX19) by functional complementation of peroxisome deficiency of a mutant Chinese hamster ovary cell line, ZP119, defective in import of both matrix and membrane proteins.","explanation":"States the import defect and that human PEX19 complements it."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Peroxisome_Biogenesis_Disorder_12A_Zellweger","model_node_id":"model:kb/disorders/Peroxisome_Biogenesis_Disorder_12A_Zellweger.yaml:CHO peroxisome-deficient mutant ZP119 (complementation group J)","focus_node_id":"node:disorder%3APeroxisome_Biogenesis_Disorder_12A_Zellweger:pathophysiology:Collapse%20of%20Peroxisomal%20Matrix%20Protein%20Import","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Peroxisome_Biogenesis_Disorder_12A_Zellweger.html#pathograph","nodes":[{"id":"model:kb/disorders/Peroxisome_Biogenesis_Disorder_12A_Zellweger.yaml:CHO peroxisome-deficient mutant ZP119 (complementation group J)","kind":"experimental_model","kind_label":"NAM model","label":"CHO peroxisome-deficient mutant ZP119 (complementation group J)","description":"A chemically derived Chinese hamster ovary mutant defective in import of both matrix and membrane proteins, later shown to be PEX19-deficient and assigned to the same complementation group as the human CG-J patients. 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It is a mammalian somatic-cell system rather than an animal model, which is why it sits here and not in `animal_models`.","url":"https://dismech.monarchinitiative.org/pages/disorders/Peroxisome_Biogenesis_Disorder_12A_Zellweger.html#experimental-model-cho-peroxisome-deficient-mutant-zp119-complementation-group-j","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APeroxisome_Biogenesis_Disorder_12A_Zellweger:pathophysiology:Collapse%20of%20Peroxisomal%20Matrix%20Protein%20Import","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Collapse of Peroxisomal Matrix Protein Import","description":"With no peroxisomal compartment, matrix enzymes remain in the cytosol, where they are degraded or left in unprocessed precursor form. 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This is the feature that separates PEX19 disease from the matrix-import peroxisome biogenesis disorders, in which membrane \"ghosts\" persist and can be stained; PEX3 and PEX16 deficiency behave the same way.","url":"https://dismech.monarchinitiative.org/pages/disorders/Peroxisome_Biogenesis_Disorder_12A_Zellweger.html#pathophysiology-absence-of-peroxisomal-membrane-compartments","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APeroxisome_Biogenesis_Disorder_12A_Zellweger:pathophysiology:Accumulation%20of%20Very-Long-Chain%20Fatty%20Acids","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Accumulation of Very-Long-Chain Fatty Acids","description":"Peroxisomes are where very-long-chain and branched-chain fatty acids are catabolised, so their absence lets these substrates accumulate. In this disorder that accumulation is usual but not invariable: the most recently reported PEX19 patient had an unremarkable very-long-chain fatty acid profile despite a homozygous nonsense allele, and normal plasma levels have been recorded in a handful of other peroxisome biogenesis disorder patients.","url":"https://dismech.monarchinitiative.org/pages/disorders/Peroxisome_Biogenesis_Disorder_12A_Zellweger.html#pathophysiology-accumulation-of-very-long-chain-fatty-acids","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APeroxisome_Biogenesis_Disorder_12A_Zellweger:pathophysiology:Congenital%20Structural%20Malformation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Congenital Structural Malformation","description":"Structural birth defects reported in this disorder. 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This study characterized 13 variants and used a 60% activity cut-off, which is an operational threshold rather than a measured physiological boundary; setting 13 against the more than 2300 variants catalogued elsewhere in this entry is a comparison drawn here, not one the paper makes.","biological_scale":"CELLULAR","anatomy":[{"id":"UBERON:0002107","label":"liver","display_label":"liver","url":"http://purl.obolibrary.org/obo/UBERON_0002107"}],"cell_types":[{"id":"CL:0000182","label":"hepatocyte","display_label":"hepatocyte","url":"http://purl.obolibrary.org/obo/CL_0000182"}],"biological_processes":[{"id":"GO:0006898","label":"receptor-mediated endocytosis","display_label":"receptor-mediated endocytosis","url":"http://purl.obolibrary.org/obo/GO_0006898"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Surface expression, LDL binding and LDL uptake by flow cytometry","description":null,"target":"Reduced Functional Hepatic LDL Receptor Activity","direction":"DECREASED","interpretation":"Residual activity below the assay threshold in one or more of the three steps is what marks an allele as functionally impairing.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:34167030","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/34167030","reference_title":"LDLR variants functional characterization: Contribution to variant classification.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"cell surface expression, binding and uptake of FITC-LDL were assessed by flow cytometry and Western blot","explanation":"Names the three measurements that constitute this readout."}],"notes":null}],"evidence":[{"reference":"PMID:34167030","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/34167030","reference_title":"LDLR variants functional characterization: Contribution to variant classification.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Different LDLR mutants were generated by site-directed mutagenesis and expressed in CHO-ldlA7 cells lacking endogenous expression of LDLR.","explanation":"Describes the null-background heterologous system, which is what lets the readout be attributed to the introduced allele."},{"reference":"PMID:34167030","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/34167030","reference_title":"LDLR variants functional characterization: Contribution to variant classification.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"LDLR mutations are the cause of disease in 90% of the cases but functional studies have only been performed for about 15% of all LDLR variants.","explanation":"Quantifies how little of the allelic series has been functionally characterized, which is the gap this class of assay exists to close."},{"reference":"PMID:34167030","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/34167030","reference_title":"LDLR variants functional characterization: Contribution to variant classification.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"cell surface expression, binding and uptake of FITC-LDL were assessed by flow cytometry and Western blot","explanation":"Names the three measurements that constitute this readout."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:LDLR-Related_Familial_Hypercholesterolemia","model_node_id":"model:kb/disorders/LDLR-Related_Familial_Hypercholesterolemia.yaml:CHO-ldlA7 heterologous LDLR variant expression assay","focus_node_id":"node:disorder%3ALDLR-Related_Familial_Hypercholesterolemia:pathophysiology:Reduced%20Functional%20Hepatic%20LDL%20Receptor%20Activity","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/LDLR-Related_Familial_Hypercholesterolemia.html#pathograph","nodes":[{"id":"model:kb/disorders/LDLR-Related_Familial_Hypercholesterolemia.yaml:CHO-ldlA7 heterologous LDLR variant expression assay","kind":"experimental_model","kind_label":"NAM model","label":"CHO-ldlA7 heterologous LDLR variant expression assay","description":"Site-directed LDLR mutants expressed in CHO-ldlA7 cells, a Chinese hamster ovary line carrying no endogenous LDL receptor, with surface expression, LDL binding and LDL uptake read out separately by flow cytometry. This is the assay behind the entry's Functional Characterization of LDLR Variants diagnostic item, and because it resolves the three steps separately it is the assay family from which class assignment is made - the class call itself is a separate claim, cited on that diagnostic item (PMID:25386756) rather than here. This paper anchors the model because it states the system and the readouts most explicitly; the larger ClinGen-linked characterization effort (PMID:34906454) is cited elsewhere in the entry.","url":"https://dismech.monarchinitiative.org/pages/disorders/LDLR-Related_Familial_Hypercholesterolemia.html#experimental-model-cho-ldla7-heterologous-ldlr-variant-expression-assay","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALDLR-Related_Familial_Hypercholesterolemia:pathophysiology:Reduced%20Functional%20Hepatic%20LDL%20Receptor%20Activity","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced Functional Hepatic LDL Receptor Activity","description":"The convergence node of the allelic series. Whichever step is broken - synthesis, ER export, ligand binding, internalization, or recycling - the measurable output is the same: fewer LDL particles cleared per unit time by the hepatocyte. Functional assays report this as a single quantity (percentage of wild-type LDL uptake), which is why class assignment and residual activity are recorded separately: the class says *where* the itinerary breaks, the residual activity says *how much* capacity survives. Null alleles are conventionally under about 2% of normal activity, though trial protocols have operationalized \"null\" at thresholds as high as 15%.","url":"https://dismech.monarchinitiative.org/pages/disorders/LDLR-Related_Familial_Hypercholesterolemia.html#pathophysiology-reduced-functional-hepatic-ldl-receptor-activity","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALDLR-Related_Familial_Hypercholesterolemia:pathophysiology:Absent%20LDL%20Receptor%20Synthesis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Absent LDL Receptor Synthesis","description":"The class 1 (null, receptor-negative) branch. No immunodetectable LDL receptor protein is made, because the allele deletes the promoter, produces no mRNA, or produces mRNA that yields no protein. This is the most severe branch and the one with the least therapeutic room: there is no receptor to upregulate. In clinical trials of homozygous disease it is operationalized as \"null-null\" or receptor-negative status.","url":"https://dismech.monarchinitiative.org/pages/disorders/LDLR-Related_Familial_Hypercholesterolemia.html#pathophysiology-absent-ldl-receptor-synthesis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALDLR-Related_Familial_Hypercholesterolemia:pathophysiology:Defective%20Clustering%20in%20Clathrin-Coated%20Pits","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Defective Clustering in Clathrin-Coated Pits","description":"The class 4 (internalization-defective) branch. The cytoplasmic tail of the LDL receptor carries the signal that concentrates it in clathrin-coated pits; a change there leaves a receptor that is expressed and binds LDL normally but is distributed diffusely over the surface and enters the cell slowly. The founding example is patient J.D., whose receptor carries a tyrosine-to-cysteine substitution at residue 807. Because the LDLRAP1/ARH adaptor serves this same step, the recessive LDLRAP1 disease is the phenocopy of this branch acting in trans.","url":"https://dismech.monarchinitiative.org/pages/disorders/LDLR-Related_Familial_Hypercholesterolemia.html#pathophysiology-defective-clustering-in-clathrin-coated-pits","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALDLR-Related_Familial_Hypercholesterolemia:pathophysiology:Defective%20Endosomal%20Ligand%20Release%20and%20Receptor%20Recycling","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Defective Endosomal Ligand Release and Receptor Recycling","description":"The class 5 (recycling-defective) branch. Binding and internalization are intact, but the receptor fails to release LDL when the endosome acidifies, so receptor and ligand traffic together to the lysosome and the receptor is consumed rather than returned to the surface. Each receptor therefore makes one round trip instead of many, and functional clearance capacity collapses even though synthesis is normal. This is also the step that PCSK9 subverts pharmacologically, which is why PCSK9-directed drugs raise receptor abundance in patients who still have recyclable receptor.","url":"https://dismech.monarchinitiative.org/pages/disorders/LDLR-Related_Familial_Hypercholesterolemia.html#pathophysiology-defective-endosomal-ligand-release-and-receptor-recycling","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALDLR-Related_Familial_Hypercholesterolemia:pathophysiology:Defective%20LDL%20Binding%20at%20the%20Hepatocyte%20Surface","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Defective LDL Binding at the Hepatocyte Surface","description":"The class 3 (binding-defective) branch. Receptor reaches the surface in normal numbers but binds apoB-100-containing LDL with reduced affinity. Changes typically fall in the cysteine-rich ligand-binding repeats or in the EGF-precursor homology domain that holds them in a binding-competent conformation. This is the receptor-side mirror of the ligand-side defect curated in Familial_Defective_Apolipoprotein_B-100 - the same handshake fails, from the other side.","url":"https://dismech.monarchinitiative.org/pages/disorders/LDLR-Related_Familial_Hypercholesterolemia.html#pathophysiology-defective-ldl-binding-at-the-hepatocyte-surface","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALDLR-Related_Familial_Hypercholesterolemia:pathophysiology:Impaired%20ER-to-Golgi%20Transport%20of%20the%20LDL%20Receptor","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired ER-to-Golgi Transport of the LDL Receptor","description":"The class 2 (transport-defective) branch. The receptor is synthesized but misfolds and is retained in the endoplasmic reticulum rather than being further glycosylated in the Golgi and delivered to the surface. Retention may be complete (class 2a) or partial (class 2b), and partial retention leaves residual surface receptor - which matters therapeutically, because residual receptor is what receptor-directed drugs act on.","url":"https://dismech.monarchinitiative.org/pages/disorders/LDLR-Related_Familial_Hypercholesterolemia.html#pathophysiology-impaired-er-to-golgi-transport-of-the-ldl-receptor","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALDLR-Related_Familial_Hypercholesterolemia:pathophysiology:Impaired%20Receptor-Mediated%20Clearance%20of%20Plasma%20LDL","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Receptor-Mediated Clearance of Plasma LDL","description":"Reduced hepatic receptor capacity lengthens the residence time of apoB-100-containing LDL and IDL in plasma. The defect is specific to the receptor's ligands: HDL clearance is unaffected, which is why the biochemical phenotype is an isolated elevation of LDL rather than a generalized dyslipidemia.","url":"https://dismech.monarchinitiative.org/pages/disorders/LDLR-Related_Familial_Hypercholesterolemia.html#pathophysiology-impaired-receptor-mediated-clearance-of-plasma-ldl","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALDLR-Related_Familial_Hypercholesterolemia:pathophysiology:Residual%20Receptor%20Activity%20Gates%20Receptor-Dependent%20LDL%20Lowering","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Residual Receptor Activity Gates Receptor-Dependent LDL Lowering","description":"The pharmacogenetic node, and the reason the allelic series is clinically actionable rather than merely descriptive. Statins lower intracellular cholesterol and thereby induce more LDL receptor; PCSK9 antibodies and inclisiran prevent or reduce PCSK9-mediated receptor degradation. Both families of drugs work by putting *more* receptor on the hepatocyte surface, so both require a receptor that can be made and can function. The genotype-stratified evidence below is for a PCSK9 antibody: in the two receptor-negative (null-null) homozygotes studied there was nothing to induce and the response was absent, while in receptor-defective homozygotes there was residual receptor and the response was preserved. Whether statins behave the same way in receptor-negative disease has not been tested here - the two null patients in that trial were already on stable statin therapy at enrolment - and the mechanisms differ (statins act transcriptionally on receptor synthesis, PCSK9-directed agents post-translationally on receptor degradation and recycling), so the statin/PCSK9 asymmetry is carried as an open question in the residual_ldlr_activity_response_threshold discussion rather than asserted. LDLR-independent agents - the MTP inhibitor lomitapide, the ANGPTL3 antibody evinacumab, and lipoprotein apheresis - bypass the receptor entirely and retain effect in null-null disease. This node is the target of the treatment entries curated below.","url":"https://dismech.monarchinitiative.org/pages/disorders/LDLR-Related_Familial_Hypercholesterolemia.html#pathophysiology-residual-receptor-activity-gates-receptor-dependent-ldl-lowering","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/LDLR-Related_Familial_Hypercholesterolemia.yaml:CHO-ldlA7 heterologous LDLR variant expression assay","source_id":"model:kb/disorders/LDLR-Related_Familial_Hypercholesterolemia.yaml:CHO-ldlA7 heterologous LDLR variant expression 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intact.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ALDLR-Related_Familial_Hypercholesterolemia:6:0","source_id":"node:disorder%3ALDLR-Related_Familial_Hypercholesterolemia:pathophysiology:Reduced%20Functional%20Hepatic%20LDL%20Receptor%20Activity","target_id":"node:disorder%3ALDLR-Related_Familial_Hypercholesterolemia:pathophysiology:Impaired%20Receptor-Mediated%20Clearance%20of%20Plasma%20LDL","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[6].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Hepatic LDL receptors perform most clearance of circulating LDL, so a fall in functional receptor activity directly lengthens LDL residence time in 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cytometry"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:34167030","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/34167030","reference_title":"LDLR variants functional characterization: Contribution to variant classification.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Different LDLR mutants were generated by site-directed mutagenesis and expressed in CHO-ldlA7 cells lacking endogenous expression of LDLR.","explanation":"Describes the null-background heterologous system, which is what lets the readout be attributed to the introduced allele."},{"reference":"PMID:34167030","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/34167030","reference_title":"LDLR variants functional characterization: Contribution to variant 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This is the system in which every human-cell observation of the CHOPS mechanism was made.","notes":null,"context_id":"disorder:CHOPS_Syndrome","context_kind":"Disorder","disease_name":"CHOPS Syndrome","disease_synonyms":["CHOPS","AFF4-related CHOPS syndrome","cognitive impairment - coarse facies - heart defects - obesity - pulmonary involvement - short stature - skeletal dysplasia syndrome"],"disease_term":{"id":"MONDO:0014609","label":"cognitive impairment - coarse facies - heart defects - obesity - pulmonary involvement - short stature - skeletal dysplasia syndrome","display_label":"CHOPS syndrome","url":"http://purl.obolibrary.org/obo/MONDO_0014609"},"experimental_model_type":"PRIMARY_CELL_CULTURE","experimental_model_type_label":"Primary-cell culture","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[{"id":"CL:0002620","label":"skin fibroblast","display_label":"skin fibroblast","url":"http://purl.obolibrary.org/obo/CL_0002620"}],"linked_cell_type_labels":["skin fibroblast"],"cell_types":[{"id":"CL:0002620","label":"skin fibroblast","display_label":"skin fibroblast","url":"http://purl.obolibrary.org/obo/CL_0002620"}],"cell_type_labels":["skin fibroblast"],"conditions":[],"cell_source":null,"source_category":"Primary / biopsy-derived","culture_system":null,"publication":"PMID:25730767","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/25730767","mechanisms":[{"target":"Accumulation of Chromatin-Associated AFF4 Protein","target_url":"https://dismech.monarchinitiative.org/pages/disorders/CHOPS_Syndrome.html#pathophysiology-accumulation-of-chromatin-associated-aff4-protein","relationship":"MEASURES","relationship_label":"Measures","fidelity":"MODERATE","fidelity_label":"Moderate","description":"Provides the direct human measurement of AFF4 protein level and its chromatin partitioning in cells carrying the endogenous variant.","limitations":"Dermal fibroblasts are not the affected lineage for any CHOPS phenotype - not lung, not cartilage, not neurons - so the magnitude and gene-selectivity of AFF4 accumulation in the tissues that actually malform is inferred, not measured. Few patient lines were available and controls were correspondingly few.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[{"id":"CL:0002620","label":"skin fibroblast","display_label":"skin fibroblast","url":"http://purl.obolibrary.org/obo/CL_0002620"}],"biological_processes":[{"id":"GO:0050821","label":"protein stabilization","display_label":"AFF4 protein stabilization","url":"http://purl.obolibrary.org/obo/GO_0050821"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Chromatin-fraction AFF4 protein abundance by western blot","description":null,"target":"Accumulation of Chromatin-Associated AFF4 Protein","direction":"INCREASED","interpretation":"The variant protein accumulates specifically on chromatin.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:25730767","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/25730767","reference_title":"Germline gain-of-function mutations in AFF4 cause a developmental syndrome functionally linking the super elongation complex and cohesin.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"accumulation of AFF4 mainly occurred on the chromatin fraction in the CHOPS syndrome cell lines","explanation":"Reports the fractionation result behind this readout."}],"notes":null}],"evidence":[{"reference":"PMID:25730767","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/25730767","reference_title":"Germline gain-of-function mutations in AFF4 cause a developmental syndrome functionally linking the super elongation complex and cohesin.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The amount of AFF4 protein in patient derived skin fibroblasts was elevated, supporting the suggestion that the missense mutations found in these probands results in a more stable AFF4 protein","explanation":"Justifies the patient fibroblast line as informative for the protein-stability mechanism."},{"reference":"PMID:25730767","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/25730767","reference_title":"Germline gain-of-function mutations in AFF4 cause a developmental syndrome functionally linking the super elongation complex and cohesin.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"accumulation of AFF4 mainly occurred on the chromatin fraction in the CHOPS syndrome cell lines","explanation":"Reports the fractionation result behind this readout."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:CHOPS_Syndrome","model_node_id":"model:kb/disorders/CHOPS_Syndrome.yaml:CHOPS patient-derived dermal fibroblasts","focus_node_id":"node:disorder%3ACHOPS_Syndrome:pathophysiology:Accumulation%20of%20Chromatin-Associated%20AFF4%20Protein","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/CHOPS_Syndrome.html#pathograph","nodes":[{"id":"model:kb/disorders/CHOPS_Syndrome.yaml:CHOPS patient-derived dermal fibroblasts","kind":"experimental_model","kind_label":"NAM model","label":"CHOPS patient-derived dermal fibroblasts","description":"Primary skin fibroblast lines from individuals carrying p.Thr254Ala, p.Thr254Ser and p.Arg258Trp, with hTERT-immortalised derivatives, compared against age- and sex-matched controls and against NIPBL-mutant CdLS fibroblasts. 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The excess partitions specifically to the chromatin fraction, and the other SEC components ELL2 and CDK9 are not correspondingly increased - so the complex is not simply more abundant; its scaffold is over-represented on chromatin. Deleting the mutant allele in a patient line lowers AFF4 back down, attributing the accumulation to the mutant allele rather than to a trans effect.","url":"https://dismech.monarchinitiative.org/pages/disorders/CHOPS_Syndrome.html#pathophysiology-accumulation-of-chromatin-associated-aff4-protein","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACHOPS_Syndrome:pathophysiology:Attenuation%20of%20Enhancer%20Complexes%20and%20Enhancer-Promoter%20Looping","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Attenuation of Enhancer Complexes and Enhancer-Promoter Looping","description":"Chromosome-architecture analysis of CHOPS and CdLS patient cell lines found cohesin, the cohesin loader NIPBL, BRD4 and H3K27ac all reduced at most enhancers, with attenuation of enhancer-promoter loops, while topologically associating domains were preserved. 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The same escape was demonstrated independently for the later alleles p.Ala255Thr and p.Pro253Arg. This is a protein-turnover defect, distinct from the abundance change it produces.","url":"https://dismech.monarchinitiative.org/pages/disorders/CHOPS_Syndrome.html#pathophysiology-loss-of-siah1-mediated-degradation-of-aff4","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/CHOPS_Syndrome.yaml:CHOPS patient-derived dermal fibroblasts","source_id":"model:kb/disorders/CHOPS_Syndrome.yaml:CHOPS patient-derived dermal fibroblasts","target_id":"node:disorder%3ACHOPS_Syndrome:pathophysiology:Accumulation%20of%20Chromatin-Associated%20AFF4%20Protein","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Measures","directed":false,"relationship":"MEASURES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"Provides the direct human measurement of AFF4 protein level and its chromatin partitioning in cells carrying the endogenous variant.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ACHOPS_Syndrome:2:1","source_id":"node:disorder%3ACHOPS_Syndrome:pathophysiology:Accumulation%20of%20Chromatin-Associated%20AFF4%20Protein","target_id":"node:disorder%3ACHOPS_Syndrome:pathophysiology:Attenuation%20of%20Enhancer%20Complexes%20and%20Enhancer-Promoter%20Looping","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[1]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"In patient cells the enhancer landscape is degraded in parallel with the elongation defect; the step from AFF4 accumulation to enhancer-complex loss is not yet resolved mechanistically.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ACHOPS_Syndrome:2:0","source_id":"node:disorder%3ACHOPS_Syndrome:pathophysiology:Accumulation%20of%20Chromatin-Associated%20AFF4%20Protein","target_id":"node:disorder%3ACHOPS_Syndrome:pathophysiology:Dysregulated%20SEC-Dependent%20Transcriptional%20Elongation","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Excess chromatin-bound AFF4 alters the genome-wide deployment of the SEC and of RNA polymerase II.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ACHOPS_Syndrome:1:0","source_id":"node:disorder%3ACHOPS_Syndrome:pathophysiology:Loss%20of%20SIAH1-Mediated%20Degradation%20of%20AFF4","target_id":"node:disorder%3ACHOPS_Syndrome:pathophysiology:Accumulation%20of%20Chromatin-Associated%20AFF4%20Protein","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Reduced clearance raises the steady-state amount of AFF4 protein.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1}]}},{"target":"Global Transcriptional Dysregulation of Developmental Gene Programmes","target_url":"https://dismech.monarchinitiative.org/pages/disorders/CHOPS_Syndrome.html#pathophysiology-global-transcriptional-dysregulation-of-developmental-gene-programmes","relationship":"MEASURES","relationship_label":"Measures","fidelity":"LOW","fidelity_label":"Low","description":"Supplies the expression-profiling and RNA-seq data defining the dysregulated gene set, and the comparison against CdLS fibroblasts.","limitations":"A fibroblast transcriptome cannot report the developmental programmes of the tissues that malform, so the reported enrichment for homeobox and skeletal-development genes is suggestive of, not equivalent to, the in vivo lesion. 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The node is behavioural and deliberately makes no hypothalamic claim - no mechanism linking AFF4 to appetite regulation has been demonstrated.","url":"https://dismech.monarchinitiative.org/pages/disorders/CHOPS_Syndrome.html#pathophysiology-food-seeking-behaviour-and-impaired-satiety","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACHOPS_Syndrome:pathophysiology:Multisystem%20Developmental%20Malformation%20and%20Growth%20Dysregulation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Multisystem Developmental Malformation and Growth Dysregulation","description":"The organism-level convergence node: craniofacial, cardiac, pulmonary, skeletal, genitourinary, ocular and neurodevelopmental structures are all affected, with linear growth failure that is not corrected by a normal growth hormone response. 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Unlike the craniofacial arm this is largely a radiographic diagnostic feature and is not usually itself disabling.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Craniometaphyseal_Dysplasia.html#pathophysiology-metaphyseal-modeling-defect","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACraniometaphyseal_Dysplasia:pathophysiology:Reduced%20ANKH-Mediated%20Pyrophosphate%20Export","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced ANKH-Mediated Pyrophosphate Export","description":"ANKH encodes a multipass transmembrane protein classically described as moving inorganic pyrophosphate (PPi) from the cytosol into the extracellular matrix. 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Notably, co-expression experiments show mutant ANK does not impair wild-type ANK, arguing against the classical dominant-negative reading of the original report.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Craniometaphyseal_Dysplasia.html#pathophysiology-reduced-ankh-mediated-pyrophosphate-export","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Craniometaphyseal_Dysplasia.yaml:CMD patient and isogenic hiPSC-derived osteoclasts","source_id":"model:kb/disorders/Craniometaphyseal_Dysplasia.yaml:CMD patient and isogenic hiPSC-derived osteoclasts","target_id":"node:disorder%3ACraniometaphyseal_Dysplasia:pathophysiology:Impaired%20Osteoclast%20Differentiation%20and%20Bone%20Resorption","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"HIGH","causal_link_type":null,"causal_link_type_label":null,"description":"Isogenic comparison attributes reduced osteoclast formation and resorption specifically to the ANKH variant in human cells.\n","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ACraniometaphyseal_Dysplasia:1:0","source_id":"node:disorder%3ACraniometaphyseal_Dysplasia:pathophysiology:Connexin%2043%20Gap%20Junction%20Dysfunction","target_id":"node:disorder%3ACraniometaphyseal_Dysplasia:pathophysiology:Impaired%20Osteoclast%20Differentiation%20and%20Bone%20Resorption","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[0]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"Actively resorbing osteoclasts carrying the mutation show reduced resorption, converging on the same effector compartment as the ANKH arm, though the intervening steps are not established.\n","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ACraniometaphyseal_Dysplasia:3:0","source_id":"node:disorder%3ACraniometaphyseal_Dysplasia:pathophysiology:Impaired%20Osteoclast%20Differentiation%20and%20Bone%20Resorption","target_id":"node:disorder%3ACraniometaphyseal_Dysplasia:pathophysiology:High%20Craniofacial%20Bone%20Mass","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[3].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Reduced osteoclastic resorption shifts the remodeling balance toward net bone accumulation.\n","intermediate_mechanisms":[],"hypothesis_groups":["impaired_bone_cell_differentiation_model"],"evidence_count":1},{"id":"causal:disorder%3ACraniometaphyseal_Dysplasia:3:1","source_id":"node:disorder%3ACraniometaphyseal_Dysplasia:pathophysiology:Impaired%20Osteoclast%20Differentiation%20and%20Bone%20Resorption","target_id":"node:disorder%3ACraniometaphyseal_Dysplasia:pathophysiology:Metaphyseal%20Modeling%20Defect","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[3].downstream[1]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Narrowing (\"funnelization\") of the metaphysis during growth requires osteoclastic resorption of the periosteal surface; when resorption is deficient the metaphysis fails to taper.\n","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ACraniometaphyseal_Dysplasia:0:1","source_id":"node:disorder%3ACraniometaphyseal_Dysplasia:pathophysiology:Reduced%20ANKH-Mediated%20Pyrophosphate%20Export","target_id":"node:disorder%3ACraniometaphyseal_Dysplasia:pathophysiology:Impaired%20Osteoclast%20Differentiation%20and%20Bone%20Resorption","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[1]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"The ANKH lesion acts cell-autonomously on the osteoclast lineage, independently of its effect on extracellular mineral chemistry.\n","intermediate_mechanisms":[],"hypothesis_groups":["impaired_bone_cell_differentiation_model"],"evidence_count":1}]}}],"mechanism_names":["Impaired Osteoclast Differentiation and Bone Resorption"],"relationships":["Recapitulates"],"fidelities":["High"],"biological_scales":["Cellular"],"system_context_sources":["Linked mechanism cell type","Linked mechanism biological scale"],"modeled_system_labels":["osteoclast","Cellular"],"biological_process_terms":[{"id":"GO:0045453","label":"bone resorption","display_label":"Bone resorption","url":"http://purl.obolibrary.org/obo/GO_0045453"}],"biological_processes":["bone resorption"],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":["Osteoclast number and resorbed bone area"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:29056330","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/29056330","reference_title":"Craniometaphyseal Dysplasia Mutations in ANKH Negatively Affect Human Induced Pluripotent Stem Cell Differentiation into Osteoclasts.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"hiPSCs from CMD patients with an in-frame deletion of Phe377 or Ser375 in ANKH are more refractory to in vitro osteoclast differentiation than control hiPSCs.","explanation":"Supports treating this human cell model as informative for the osteoclast node."},{"reference":"PMID:29056330","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/29056330","reference_title":"Craniometaphyseal Dysplasia Mutations in ANKH Negatively Affect Human Induced Pluripotent Stem Cell Differentiation into Osteoclasts.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Isogenic hiPSCs with ANKH mutations formed fewer osteoclasts, resorbed less bone, expressed lower levels of osteoclast marker genes, and showed decreased protein levels of ANKH and vacuolar proton pump v-ATP6v0d2.","explanation":"The osteoclast count and resorption measurements behind this readout."}],"evidence_text":["hiPSCs from CMD patients with an in-frame deletion of Phe377 or Ser375 in ANKH are more refractory to in vitro osteoclast differentiation than control hiPSCs.","Isogenic hiPSCs with ANKH mutations formed fewer osteoclasts, resorbed less bone, expressed lower levels of osteoclast marker genes, and showed decreased protein levels of ANKH and vacuolar proton pump v-ATP6v0d2.","Supports treating this human cell model as informative for the osteoclast node.","The osteoclast count and resorption measurements behind this readout."],"evidence_status":"Evidence recorded","metadata_completeness":40,"metadata_present":["Model category","Cell type","Modeled mechanism","Evidence"],"metadata_missing":["NAMO class","Organism","Anatomy","Cell source","Culture system","Publication"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Craniometaphyseal_Dysplasia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Craniometaphyseal_Dysplasia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Craniometaphyseal_Dysplasia.html#experimental-model-cmd-patient-and-isogenic-hipsc-derived-osteoclasts","source_anchor":"experimental-model-cmd-patient-and-isogenic-hipsc-derived-osteoclasts"},{"id":"model:kb/disorders/Constitutional_Mismatch_Repair_Deficiency.yaml:CMMRD patient-derived lymphoblastoid cell lines (MSI and methylation-tolerance assay)","name":"CMMRD patient-derived lymphoblastoid cell lines (MSI and methylation-tolerance assay)","description":"Lymphoblastoid cells from CMMRD patients and MMR-proficient controls, assayed for microsatellite instability by PCR and for tolerance to methylating and thiopurine agents. This is the human ex vivo system in which the two defining constitutional consequences of biallelic MMR loss - instability in normal (non-tumour) cells, and loss of the MMR-dependent damage response - are measured directly, and it is also the basis of a diagnostic assay for the 30% of patients whose gene screening is uninformative.","notes":null,"context_id":"disorder:Constitutional_Mismatch_Repair_Deficiency","context_kind":"Disorder","disease_name":"Constitutional Mismatch Repair Deficiency","disease_synonyms":["CMMRD","constitutional mismatch repair deficiency syndrome","biallelic mismatch repair deficiency","bMMRD","childhood cancer syndrome with biallelic mismatch repair deficiency"],"disease_term":{"id":"MONDO:0031219","label":"mismatch repair cancer syndrome","display_label":"constitutional mismatch repair deficiency syndrome","url":"http://purl.obolibrary.org/obo/MONDO_0031219"},"experimental_model_type":"CELL_LINE","experimental_model_type_label":"Cell line","namo_type":"namo:CellLineModel","declared_namo_class_name":null,"namo_class_name":"CellLineModel","namo_class_label":"Cell Line Model","namo_description":"A model system based on immortalized cell lines that can be maintained in culture indefinitely. Examples: HepG2, A549, Caco-2, etc.","namo_docs_url":"https://monarch-initiative.github.io/namo/elements/CellLineModel/","namo_ontology_url":"https://w3id.org/monarch-initiative/namo/CellLineModel","namo_mapping_basis":"Safe mapping from DisMech category","namo_class_in_schema":true,"namo_schema_status":"Defined in NAMO schema used for this build","modality":"Cellular system","organism":{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},"organism_label":"Homo sapiens","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[{"id":"GO:0005634","label":"nucleus","display_label":"nucleus","url":"http://purl.obolibrary.org/obo/GO_0005634"}],"linked_anatomy_labels":["nucleus"],"anatomy":[{"id":"GO:0005634","label":"nucleus","display_label":"nucleus","url":"http://purl.obolibrary.org/obo/GO_0005634"}],"anatomy_labels":["nucleus"],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[{"id":"CL:0002250","label":"intestinal crypt stem cell","display_label":"intestinal crypt stem cell","url":"http://purl.obolibrary.org/obo/CL_0002250"},{"id":"CL:0000047","label":"neural stem cell","display_label":"neural stem cell","url":"http://purl.obolibrary.org/obo/CL_0000047"},{"id":"CL:0000037","label":"hematopoietic stem cell","display_label":"hematopoietic stem cell","url":"http://purl.obolibrary.org/obo/CL_0000037"}],"linked_cell_type_labels":["intestinal crypt stem cell","neural stem cell","hematopoietic stem cell"],"cell_types":[{"id":"CL:0002250","label":"intestinal crypt stem cell","display_label":"intestinal crypt stem cell","url":"http://purl.obolibrary.org/obo/CL_0002250"},{"id":"CL:0000047","label":"neural stem cell","display_label":"neural stem cell","url":"http://purl.obolibrary.org/obo/CL_0000047"},{"id":"CL:0000037","label":"hematopoietic stem cell","display_label":"hematopoietic stem cell","url":"http://purl.obolibrary.org/obo/CL_0000037"}],"cell_type_labels":["intestinal crypt stem cell","neural stem cell","hematopoietic stem cell"],"conditions":[],"cell_source":"Patient-derived (EBV-immortalized peripheral blood lymphocytes)","source_category":"Patient-derived","culture_system":null,"publication":"PMID:26116798","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/26116798","mechanisms":[{"target":"Constitutional Microsatellite Instability and Mutator Phenotype","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Constitutional_Mismatch_Repair_Deficiency.html#pathophysiology-constitutional-microsatellite-instability-and-mutator-phenotype","relationship":"MEASURES","relationship_label":"Measures","fidelity":"HIGH","fidelity_label":"High","description":"Microsatellite instability is measured in normal patient-derived cells rather than in tumour, which is exactly the constitutional claim this node makes and the feature that separates CMMRD from Lynch syndrome.","limitations":"EBV-immortalized lymphoblastoid cells are a proliferating lymphoid compartment and cannot report the tissue gradient in constitutional instability that the tumour-spectrum knowledge gap concerns; instability measured in this compartment says nothing about brain or intestine.","biological_scale":"CELLULAR","anatomy":[{"id":"GO:0005634","label":"nucleus","display_label":"nucleus","url":"http://purl.obolibrary.org/obo/GO_0005634"}],"cell_types":[{"id":"CL:0002250","label":"intestinal crypt stem cell","display_label":"intestinal crypt stem cell","url":"http://purl.obolibrary.org/obo/CL_0002250"},{"id":"CL:0000047","label":"neural stem cell","display_label":"neural stem cell","url":"http://purl.obolibrary.org/obo/CL_0000047"},{"id":"CL:0000037","label":"hematopoietic stem cell","display_label":"hematopoietic stem cell","url":"http://purl.obolibrary.org/obo/CL_0000037"}],"biological_processes":[{"id":"GO:0006281","label":"DNA repair","display_label":"DNA repair","url":"http://purl.obolibrary.org/obo/GO_0006281"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Microsatellite instability in lymphoblastoid cells","description":"PCR-based MSI analysis of patient versus control lymphoblastoid lines.","target":"Constitutional Microsatellite Instability and Mutator Phenotype","direction":"INCREASED","interpretation":"Instability present in non-neoplastic patient cells is the direct measurement of the constitutional mutator phenotype.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:26116798","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/26116798","reference_title":"Diagnosis of Constitutional Mismatch Repair-Deficiency Syndrome Based on Microsatellite Instability and Lymphocyte Tolerance to Methylating Agents.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"In the training set, we identified parameters, based on MSI and LC tolerance to methylation, that detected patients with CMMRD vs controls with 100% sensitivity and 100% specificity.","explanation":"The measurement separates patients from controls without error in the training set."}],"notes":null}],"evidence":[{"reference":"PMID:26116798","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/26116798","reference_title":"Diagnosis of Constitutional Mismatch Repair-Deficiency Syndrome Based on Microsatellite Instability and Lymphocyte Tolerance to Methylating Agents.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Using these assays, we defined experimental parameters that allowed discrimination of a series of 14 patients with CMMRD from 52 controls (training set).","explanation":"Supports treating this cell system as informative for the constitutional instability node, at a cohort size that establishes the parameters rather than illustrating them."},{"reference":"PMID:26116798","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/26116798","reference_title":"Diagnosis of Constitutional Mismatch Repair-Deficiency Syndrome Based on Microsatellite Instability and Lymphocyte Tolerance to Methylating Agents.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"In the training set, we identified parameters, based on MSI and LC tolerance to methylation, that detected patients with CMMRD vs controls with 100% sensitivity and 100% specificity.","explanation":"The measurement separates patients from controls without error in the training set."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Constitutional_Mismatch_Repair_Deficiency","model_node_id":"model:kb/disorders/Constitutional_Mismatch_Repair_Deficiency.yaml:CMMRD patient-derived lymphoblastoid cell lines (MSI and methylation-tolerance assay)","focus_node_id":"node:disorder%3AConstitutional_Mismatch_Repair_Deficiency:pathophysiology:Constitutional%20Microsatellite%20Instability%20and%20Mutator%20Phenotype","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Constitutional_Mismatch_Repair_Deficiency.html#pathograph","nodes":[{"id":"model:kb/disorders/Constitutional_Mismatch_Repair_Deficiency.yaml:CMMRD patient-derived lymphoblastoid cell lines (MSI and methylation-tolerance assay)","kind":"experimental_model","kind_label":"NAM model","label":"CMMRD patient-derived lymphoblastoid cell lines (MSI and methylation-tolerance assay)","description":"Lymphoblastoid cells from CMMRD patients and MMR-proficient controls, assayed for microsatellite instability by PCR and for tolerance to methylating and thiopurine agents. 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Constitutional MSI is therefore both the mechanistic core of the syndrome and its most discriminating diagnostic assay.","url":"https://dismech.monarchinitiative.org/pages/disorders/Constitutional_Mismatch_Repair_Deficiency.html#pathophysiology-constitutional-microsatellite-instability-and-mutator-phenotype","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3AConstitutional_Mismatch_Repair_Deficiency:pathophysiology:Accelerated%20Multi-Organ%20Tumorigenesis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Accelerated Multi-Organ Tumorigenesis","description":"The constitutional mutator state converts every proliferative compartment into a site of accelerated clonal evolution, so tumours arise early, in multiple organs, and repeatedly over a lifetime rather than as a single event. In the IRRDC cohort 339 cancers occurred in 97% of 201 patients, the median interval between successive cancers was under two years, and neoplasms arose in fifteen different organs. CNS tumours dominate and carry the worst survival; gastrointestinal and haematological malignancies follow. Low-grade lesions are not indolent - the great majority progress to high grade within a few years if not resected, which is what makes structured surveillance rather than symptom-driven presentation the decisive management variable.","url":"https://dismech.monarchinitiative.org/pages/disorders/Constitutional_Mismatch_Repair_Deficiency.html#pathophysiology-accelerated-multi-organ-tumorigenesis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3AConstitutional_Mismatch_Repair_Deficiency:pathophysiology:Biallelic%20Germline%20Mismatch%20Repair%20Gene%20Inactivation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Biallelic Germline Mismatch Repair Gene Inactivation","description":"Both alleles of MLH1, MSH2, MSH6 or PMS2 carry a pathogenic variant in the germ line (homozygous or compound heterozygous). 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This is the point at which CMMRD diverges from Lynch syndrome, where the second allele is intact until a somatic hit occurs in one tissue.","url":"https://dismech.monarchinitiative.org/pages/disorders/Constitutional_Mismatch_Repair_Deficiency.html#pathophysiology-biallelic-germline-mismatch-repair-gene-inactivation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3AConstitutional_Mismatch_Repair_Deficiency:pathophysiology:Loss%20of%20MMR-Dependent%20Damage%20Signalling%20and%20Alkylating%20Agent%20Tolerance","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Loss of MMR-Dependent Damage Signalling and Alkylating Agent Tolerance","description":"Beyond error correction, MutSalpha/MutLalpha are required to convert persistent O6-methylguanine mispairs into a cytotoxic signal. 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This is a therapeutically decisive consequence: standard glioma protocols cannot be applied reflexively in CMMRD.","url":"https://dismech.monarchinitiative.org/pages/disorders/Constitutional_Mismatch_Repair_Deficiency.html#pathophysiology-loss-of-mmr-dependent-damage-signalling-and-alkylating-agent-tolerance","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3AConstitutional_Mismatch_Repair_Deficiency:pathophysiology:Somatic%20Polymerase%20Proofreading%20Loss%20and%20Ultra-Hypermutation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Somatic Polymerase Proofreading Loss and Ultra-Hypermutation","description":"An early somatic mutation in the exonuclease (proofreading) domain of POLE or POLD1 is frequently acquired and selected in CMMRD high-grade tumours - every ultra-hypermutated tumour in the index series carried one. Loss of proofreading on top of absent mismatch repair removes both layers of replication-error correction, and mutations then accumulate in a rapid burst rather than gradually. The resulting ultra-hypermutant genome (in excess of 100, and in brain tumours often over 250, mutations per megabase) is the highest burden recorded in human cancer and carries a strand-biased signature attributable to the mutant polymerase.","url":"https://dismech.monarchinitiative.org/pages/disorders/Constitutional_Mismatch_Repair_Deficiency.html#pathophysiology-somatic-polymerase-proofreading-loss-and-ultra-hypermutation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"}],"edges":[{"id":"model-link:0:model:kb/disorders/Constitutional_Mismatch_Repair_Deficiency.yaml:CMMRD patient-derived lymphoblastoid cell lines (MSI and methylation-tolerance assay)","source_id":"model:kb/disorders/Constitutional_Mismatch_Repair_Deficiency.yaml:CMMRD patient-derived lymphoblastoid cell lines (MSI and 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and characterization of three human pluripotent stem cell lines from Charcot-Marie-Tooth disease Type 4B3 patients bearing mutations in MTMR5/Sbf1 gene.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Here, we describe the establishment and validation of three human induced pluripotent stem cell (iPSC) lines derived from unrelated CMT4B3 patients, each harboring homozygous MTMR5/Sbf1 mutations.","explanation":"Establishes the existence and provenance of these lines."},{"reference":"PMID:36272304","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/36272304","reference_title":"Generation and characterization of CSSi016-A (9938) human pluripotent stem cell line carrying two biallelic variants in MTMR5/SBF1 gene resulting in a case of severe CMT4B3.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Herein, we report the generation and characterization of a hiPSC line from a 12-year-old Italian girl with early onset severe polyneuropathy with motor and axonal involvement, harboring biallelic variants in the MTMR5/SBF1 gene.","explanation":"A fourth line, from the severe infantile axonal case whose fibroblasts carry the mitochondrial phenotype recorded above."}],"evidence_text":["Here, we describe the establishment and validation of three human induced pluripotent stem cell (iPSC) lines derived from unrelated CMT4B3 patients, each harboring homozygous MTMR5/Sbf1 mutations.","Herein, we report the generation and characterization of a hiPSC line from a 12-year-old Italian girl with early onset severe polyneuropathy with motor and axonal involvement, harboring biallelic variants in the MTMR5/SBF1 gene.","Establishes the existence and provenance of these lines.","A fourth line, from the severe infantile axonal case whose fibroblasts carry the mitochondrial phenotype recorded above."],"evidence_status":"Evidence recorded","metadata_completeness":40,"metadata_present":["Model category","Organism","Publication","Evidence"],"metadata_missing":["NAMO 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The cells also grow poorly, which the 2025 authors identify as a practical limit on further experimentation.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0033617","label":"mitochondrial respiratory chain complex IV assembly","display_label":"mitochondrial respiratory chain complex IV assembly","url":"http://purl.obolibrary.org/obo/GO_0033617"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Complex IV assembly intermediates on 2D-BN PAGE","description":null,"target":"Arrested Early Complex IV Assembly","direction":"INCREASED","interpretation":"Accumulation of a small COX1-containing intermediate lacking COX2, COX4 and COX5b is the direct structural readout of the arrested assembly step.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:21457908","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/21457908","reference_title":"A mutation in C2orf64 causes impaired 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background.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:21457908","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/21457908","reference_title":"A mutation in C2orf64 causes impaired cytochrome c oxidase assembly and mitochondrial cardiomyopathy.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"complex IV activity can be fully restored by retroviral transduction of wild-type C2orf64 in patient-derived fibroblasts","explanation":"Reports the rescue measurement in the patient fibroblast model."}],"notes":null}],"evidence":[{"reference":"PMID:39779219","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39779219","reference_title":"COA5 has an essential role in the early stage of mitochondrial complex IV assembly.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"CIV protein subunits exhibited a statistically significant decrease in protein abundance up to almost fourfold, whereas CI, CII, CIII, and CV 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Complete loss of the holocomplex in knockout cells should not be equated with complete loss in patient fibroblasts.","url":"https://dismech.monarchinitiative.org/pages/disorders/COA5-Related_Fatal_Infantile_Cardioencephalomyopathy.html#pathophysiology-arrested-early-complex-iv-assembly","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACOA5-Related_Fatal_Infantile_Cardioencephalomyopathy:pathophysiology:Disrupted%20COX2%20Metallochaperone%20Interactions","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Disrupted COX2 Metallochaperone Interactions","description":"In PET191/COA5 knockout HEK293T cells, newly synthesized COX2 fails to interact with SCO1, COA6 and COX16. These experiments support a COA5-dependent metallochaperone assembly function, but do not establish that p.Ala53Pro disrupts each interaction identically.","url":"https://dismech.monarchinitiative.org/pages/disorders/COA5-Related_Fatal_Infantile_Cardioencephalomyopathy.html#pathophysiology-disrupted-cox2-metallochaperone-interactions","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ACOA5-Related_Fatal_Infantile_Cardioencephalomyopathy:pathophysiology:Impaired%20COA5%20Assembly-Factor%20Function","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired COA5 Assembly-Factor Function","description":"Homozygous COA5 p.Ala53Pro impairs assembly-factor function. Wild-type COA5 complementation restores complex IV activity in patient fibroblasts. This functional defect does not establish complete absence of the missense protein; the null cell models are distinct experimental perturbations.","url":"https://dismech.monarchinitiative.org/pages/disorders/COA5-Related_Fatal_Infantile_Cardioencephalomyopathy.html#pathophysiology-impaired-coa5-assembly-factor-function","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACOA5-Related_Fatal_Infantile_Cardioencephalomyopathy:pathophysiology:Loss%20of%20Complex%20IV-Containing%20Supercomplexes","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Loss of Complex IV-Containing Supercomplexes","description":"COA5 knockout U2OS cells lose the III2+IV supercomplex and accumulate I+III2 assemblies. 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These are genotype- and system-specific observations, not a universal absence of complex assembly.","url":"https://dismech.monarchinitiative.org/pages/disorders/COG4-Congenital_Disorder_of_Glycosylation.html#pathophysiology-reduced-cog4-expression","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/COG4-Congenital_Disorder_of_Glycosylation.yaml:COG4-CDG patient fibroblasts","source_id":"model:kb/disorders/COG4-Congenital_Disorder_of_Glycosylation.yaml:COG4-CDG patient fibroblasts","target_id":"node:disorder%3ACOG4-Congenital_Disorder_of_Glycosylation:pathophysiology:Delayed%20Golgi%20retrograde%20transport","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ACOG4-Congenital_Disorder_of_Glycosylation:2:0","source_id":"node:disorder%3ACOG4-Congenital_Disorder_of_Glycosylation:pathophysiology:Delayed%20Golgi%20retrograde%20transport","target_id":"node:disorder%3ACOG4-Congenital_Disorder_of_Glycosylation:pathophysiology:Proposed%20altered%20Golgi%20enzyme%20recycling","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[0]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ACOG4-Congenital_Disorder_of_Glycosylation:1:0","source_id":"node:disorder%3ACOG4-Congenital_Disorder_of_Glycosylation:pathophysiology:Reduced%20COG4%20Expression","target_id":"node:disorder%3ACOG4-Congenital_Disorder_of_Glycosylation:pathophysiology:Delayed%20Golgi%20retrograde%20transport","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[0]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1}]}},{"target":"Abnormal O-glycan processing","target_url":"https://dismech.monarchinitiative.org/pages/disorders/COG4-Congenital_Disorder_of_Glycosylation.html#pathophysiology-abnormal-o-glycan-processing","relationship":"PARTIALLY_RECAPITULATES","relationship_label":"Partially Recapitulates","fidelity":"MODERATE","fidelity_label":"Moderate","description":null,"limitations":"GAP is an artificial acceptor of glycan biosynthesis; 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For the recurrent c.637+1G>T allele, exon skipping was demonstrated in a minigene assay and truncation is predicted if the abnormal transcript escapes nonsense-mediated decay; endogenous mutant protein abundance in patient hair cells was not measured.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Recessive_Nonsyndromic_Hearing_Loss_93.html#pathophysiology-biallelic-cabp2-loss-of-function-variant","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAutosomal_Recessive_Nonsyndromic_Hearing_Loss_93:pathophysiology:Loss%20of%20CaBP2%20Function%20at%20the%20Inner%20Hair%20Cell%20Ribbon%20Synapse","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Loss of CaBP2 Function at the Inner Hair Cell Ribbon Synapse","description":"CaBP2 regulates presynaptic calcium channels in cochlear inner hair cells. The founding truncation proxy showed altered calcium binding and weaker, but retained, inhibition of CaV1.3 inactivation. In mice, a genetic expression reporter localized Cabp2 to inner and outer hair cells but not spiral ganglion neurons, supporting a presynaptic site of the principal sound-encoding defect.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Recessive_Nonsyndromic_Hearing_Loss_93.html#pathophysiology-loss-of-cabp2-function-at-the-inner-hair-cell-ribbon-synapse","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Autosomal_Recessive_Nonsyndromic_Hearing_Loss_93.yaml:COS-7 CABP2 exon-trapping assay","source_id":"model:kb/disorders/Autosomal_Recessive_Nonsyndromic_Hearing_Loss_93.yaml:COS-7 CABP2 exon-trapping assay","target_id":"node:disorder%3AAutosomal_Recessive_Nonsyndromic_Hearing_Loss_93:pathophysiology:CABP2%20Exon%206%20Skipping","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AAutosomal_Recessive_Nonsyndromic_Hearing_Loss_93:0:0","source_id":"node:disorder%3AAutosomal_Recessive_Nonsyndromic_Hearing_Loss_93:pathophysiology:Biallelic%20CABP2%20Loss-of-Function%20Variant","target_id":"node:disorder%3AAutosomal_Recessive_Nonsyndromic_Hearing_Loss_93:pathophysiology:CABP2%20Exon%206%20Skipping","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"The c.637+1G>T splice-donor allele causes exon 6 skipping in a COS-7 minigene assay.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3AAutosomal_Recessive_Nonsyndromic_Hearing_Loss_93:1:0","source_id":"node:disorder%3AAutosomal_Recessive_Nonsyndromic_Hearing_Loss_93:pathophysiology:CABP2%20Exon%206%20Skipping","target_id":"node:disorder%3AAutosomal_Recessive_Nonsyndromic_Hearing_Loss_93:pathophysiology:Loss%20of%20CaBP2%20Function%20at%20the%20Inner%20Hair%20Cell%20Ribbon%20Synapse","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"The predicted truncation removes C-terminal EF hands. An engineered p.Phe164Ter proxy has altered calcium binding and weakened, residual CaV1.3 regulation.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0}]}}],"mechanism_names":["CABP2 Exon 6 Skipping"],"relationships":["Recapitulates"],"fidelities":["Moderate"],"biological_scales":["Molecular"],"system_context_sources":["Linked mechanism biological scale"],"modeled_system_labels":["Molecular"],"biological_process_terms":[],"biological_processes":[],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":[],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"url:https://pmc.ncbi.nlm.nih.gov/articles/PMC3484643/","reference_url":null,"reference_title":"A Mutation in CABP2, Expressed in Cochlear Hair Cells, Causes Autosomal-Recessive Hearing Impairment - PMC","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Analysis of cDNA prepared from COS-7 cells transfected with a MT ... donor site only revealed a PCR product of 177 bp, indicating that the mutation ... leads to a complete skipping of exon 6","explanation":"The mutant exon-trapping construct skipped exon 6 in COS-7 cells; this does not establish transcript stability in patient hair cells."}],"evidence_text":["Analysis of cDNA prepared from COS-7 cells transfected with a MT ... donor site only revealed a PCR product of 177 bp, indicating that the mutation ... leads to a complete skipping of exon 6","The mutant exon-trapping construct skipped exon 6 in COS-7 cells; this does not establish transcript stability in patient hair cells."],"evidence_status":"Evidence recorded","metadata_completeness":40,"metadata_present":["Model category","NAMO class","Modeled mechanism","Evidence"],"metadata_missing":["Organism","Anatomy","Cell type","Cell source","Culture system","Publication"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Autosomal_Recessive_Nonsyndromic_Hearing_Loss_93.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autosomal_Recessive_Nonsyndromic_Hearing_Loss_93.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Recessive_Nonsyndromic_Hearing_Loss_93.html#experimental-model-cos-7-cabp2-exon-trapping-assay","source_anchor":"experimental-model-cos-7-cabp2-exon-trapping-assay"},{"id":"model:kb/disorders/Vein_of_Galen_Aneurysm.yaml:COS-7 cells expressing VOGM-associated EPHB4 kinase-domain variants","name":"COS-7 cells expressing VOGM-associated EPHB4 kinase-domain variants","description":"A reductionist cell-line assay used to separate mutant-protein abundance from kinase function. 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Typed with unknown intermediates because no mechanism connecting cristae architecture to mtDNA copy number has been demonstrated here, and because the other three reports did not measure copy number at all.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0}]}},{"target":"Combined Respiratory Chain Deficiency","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Oxidative_Phosphorylation_Defect_Type_37.html#pathophysiology-combined-respiratory-chain-deficiency","relationship":"FAILS_TO_RECAPITULATE","relationship_label":"Fails To Recapitulate","fidelity":"LOW","fidelity_label":"Low","description":"The knockout does not reproduce the combined respiratory chain deficiency. Complex assembly is unaffected and respiration falls only moderately.","limitations":"This is a negative result in a transformed human cell line, not in an affected organ. 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The model therefore cannot settle whether the architectural lesion is insufficient to cause the deficiency, or whether the cellular context needed to reveal it is missing - but it does mean the entry's chain from cristae collapse to combined deficiency is not demonstrated in the one system where the lesion is isolated.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0006119","label":"oxidative phosphorylation","display_label":"oxidative phosphorylation","url":"http://purl.obolibrary.org/obo/GO_0006119"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Respiratory chain complex assembly and respiration rate in MIC13-knockout cells","description":null,"target":"Combined Respiratory Chain Deficiency","direction":"UNCHANGED","interpretation":"Complex assembly is preserved; the respiration decrement is moderate rather than the severe combined deficiency seen in patient tissue.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:27479602","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/27479602","reference_title":"Mic13 Is Essential for Formation of Crista Junctions in Mammalian Cells.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"MIC13 is also dispensable for assembly of respiratory chain complexes and for maintaining mitochondrial network morphology. Still, lack of MIC13 resulted in a moderate reduction of mitochondrial respiration.","explanation":"The measurement behind the negative result, including the moderate respiration decrement that did occur."}],"notes":null}],"evidence":[{"reference":"PMID:27479602","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/27479602","reference_title":"Mic13 Is Essential for Formation of Crista Junctions in Mammalian Cells.","supports":"REFUTE","evidence_source":"IN_VITRO","snippet":"we show that MIC13 has a fundamental role in crista junction formation and that assembly of respiratory chain supercomplexes is independent of mitochondrial cristae shape.","explanation":"The authors' own conclusion, which contradicts the simplest reading of this entry's causal chain. Recorded as REFUTE against the link rather than omitted, because the chain from cristae collapse to combined respiratory deficiency is the entry's central claim and this is the strongest evidence against it."},{"reference":"PMID:27479602","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/27479602","reference_title":"Mic13 Is Essential for Formation of Crista Junctions in Mammalian Cells.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"MIC13 is also dispensable for assembly of respiratory chain complexes and for maintaining mitochondrial network morphology. Still, lack of MIC13 resulted in a moderate reduction of mitochondrial respiration.","explanation":"The measurement behind the negative result, including the moderate respiration decrement that did occur."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Combined_Oxidative_Phosphorylation_Defect_Type_37","model_node_id":"model:kb/disorders/Combined_Oxidative_Phosphorylation_Defect_Type_37.yaml:CRISPR MIC13-knockout human cell line","focus_node_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Defect_Type_37:pathophysiology:Combined%20Respiratory%20Chain%20Deficiency","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Oxidative_Phosphorylation_Defect_Type_37.html#pathograph","nodes":[{"id":"model:kb/disorders/Combined_Oxidative_Phosphorylation_Defect_Type_37.yaml:CRISPR MIC13-knockout human cell line","kind":"experimental_model","kind_label":"NAM model","label":"CRISPR MIC13-knockout human cell line","description":"The first cell line deleted for MIC13, made with CRISPR/Cas in human cells. Where the patient fibroblasts show the lesion sitting alongside the disease, a knockout in a clean genetic background shows that removing MIC13 is by itself enough to abolish cristae junctions.\nThis model also separates the entry's two mechanistic claims, and the separation is informative rather than tidy. Cristae junctions are lost completely and the assembly of MIC10, MIC26 and MIC27 into MICOS fails, exactly as in patients. Respiratory chain complex assembly, by contrast, is unaffected and respiration falls only moderately, so the model does not reproduce the combined respiratory chain deficiency that names the human disease. Either the human deficiency needs something this model does not have - an affected tissue, a developmental context, time - or the architectural lesion is not a sufficient cause of it.","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Oxidative_Phosphorylation_Defect_Type_37.html#experimental-model-crispr-mic13-knockout-human-cell-line","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Defect_Type_37:pathophysiology:Combined%20Respiratory%20Chain%20Deficiency","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Combined Respiratory Chain Deficiency","description":"Multiple OXPHOS complexes are deficient at once, in liver and muscle. \"Combined\" is the diagnostic label and it is also the mechanistic clue: a defect in one complex's subunits or assembly factors affects that complex, whereas a defect in the membrane they all occupy affects all of them.\nThe strongest evidence that this is secondary to the architectural lesion rather than an independent problem is a rescue: expressing wild-type MICOS13 in the patient's own fibroblasts restored respiratory chain function.","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Oxidative_Phosphorylation_Defect_Type_37.html#pathophysiology-combined-respiratory-chain-deficiency","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Defect_Type_37:pathophysiology:Lactic%20Acidosis%20and%20Hepato-Encephalopathy","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Lactic Acidosis and Hepato-Encephalopathy","description":"The clinical endpoint: a severe infantile encephalopathy with liver disease and lactic acidosis. Fatal in the first reported patient.","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Oxidative_Phosphorylation_Defect_Type_37.html#pathophysiology-lactic-acidosis-and-hepato-encephalopathy","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Defect_Type_37:pathophysiology:Loss%20of%20Cristae%20Junctions%20and%20Inner%20Membrane%20Contact%20Sites","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Loss of Cristae Junctions and Inner Membrane Contact Sites","description":"The structural lesion of the disease. Cristae junctions are the narrow necks that connect each crista to the inner boundary membrane, and they do two things: they hold the folded surface area on which respiratory complexes are concentrated, and they partition the intermembrane space so that the crista lumen is a distinct compartment. Contact sites link the inner membrane to the outer.\nLosing them is therefore not simply a morphological finding. It removes the geometry that makes oxidative phosphorylation efficient, which is why an architectural defect presents as a bioenergetic disease.","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Oxidative_Phosphorylation_Defect_Type_37.html#pathophysiology-loss-of-cristae-junctions-and-inner-membrane-contact-sites","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:2:model:kb/disorders/Combined_Oxidative_Phosphorylation_Defect_Type_37.yaml:CRISPR MIC13-knockout human cell line","source_id":"model:kb/disorders/Combined_Oxidative_Phosphorylation_Defect_Type_37.yaml:CRISPR MIC13-knockout human cell line","target_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Defect_Type_37:pathophysiology:Combined%20Respiratory%20Chain%20Deficiency","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[2]","label":"Fails To Recapitulate","directed":false,"relationship":"FAILS_TO_RECAPITULATE","fidelity":"LOW","causal_link_type":null,"causal_link_type_label":null,"description":"The knockout does not reproduce the combined respiratory chain deficiency. Complex assembly is unaffected and respiration falls only moderately.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ACombined_Oxidative_Phosphorylation_Defect_Type_37:3:0","source_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Defect_Type_37:pathophysiology:Combined%20Respiratory%20Chain%20Deficiency","target_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Defect_Type_37:pathophysiology:Lactic%20Acidosis%20and%20Hepato-Encephalopathy","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[3].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Impaired ATP production in the two most oxidative organs, with lactate accumulating as glycolysis substitutes.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ACombined_Oxidative_Phosphorylation_Defect_Type_37:2:0","source_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Defect_Type_37:pathophysiology:Loss%20of%20Cristae%20Junctions%20and%20Inner%20Membrane%20Contact%20Sites","target_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Defect_Type_37:pathophysiology:Combined%20Respiratory%20Chain%20Deficiency","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"The complexes are intact but the membrane they work in is not.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0}]}}],"mechanism_names":["Failure of MICOS Complex Assembly","Loss of Cristae Junctions and Inner Membrane Contact Sites","Combined Respiratory Chain Deficiency"],"relationships":["Recapitulates","Fails To Recapitulate"],"fidelities":["High","Low"],"biological_scales":["Molecular","Cellular"],"system_context_sources":["Linked mechanism biological scale"],"modeled_system_labels":["Molecular","Cellular"],"biological_process_terms":[{"id":"GO:0042407","label":"cristae formation","display_label":"cristae formation","url":"http://purl.obolibrary.org/obo/GO_0042407"},{"id":"GO:0006119","label":"oxidative phosphorylation","display_label":"oxidative phosphorylation","url":"http://purl.obolibrary.org/obo/GO_0006119"}],"biological_processes":["cristae formation","oxidative phosphorylation"],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":["Assembly of MIC10, MIC26 and MIC27 into the MICOS complex","Crista junction formation in MIC13-knockout mitochondria","Respiratory chain complex assembly and respiration rate in MIC13-knockout cells"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:27479602","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/27479602","reference_title":"Mic13 Is Essential for Formation of Crista Junctions in Mammalian Cells.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We show that MIC13 is an inner membrane protein physically interacting with MIC60, a central subunit of the MICOS complex.","explanation":"Establishes the molecular relationship the model is built to interrogate, which is what makes a MIC13 deletion informative about MICOS architecture."},{"reference":"PMID:27479602","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/27479602","reference_title":"Mic13 Is Essential for Formation of Crista Junctions in Mammalian Cells.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Using the CRISPR/Cas method we generated the first cell line deleted for MIC13.","explanation":"Establishes the model as a clean deletion rather than a patient-derived system, so results in it are attributable to MIC13 loss alone."},{"reference":"PMID:27479602","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/27479602","reference_title":"Mic13 Is Essential for Formation of Crista Junctions in Mammalian Cells.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"MIC13 is required for the assembly of MIC10, MIC26, and MIC27 into the MICOS complex. However, it is not needed for the formation of the MIC60/MIC19/MIC25 subcomplex","explanation":"Names both halves of the selectivity: which subcomplex fails and which is spared."},{"reference":"PMID:27479602","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/27479602","reference_title":"Mic13 Is Essential for Formation of Crista Junctions in Mammalian Cells.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"These knockout cells show a complete loss of crista junctions demonstrating that MIC13 is strictly required for the formation of crista junctions.","explanation":"The direct measurement, in the model where the lesion is the only variable."},{"reference":"PMID:27479602","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/27479602","reference_title":"Mic13 Is Essential for Formation of Crista Junctions in Mammalian Cells.","supports":"REFUTE","evidence_source":"IN_VITRO","snippet":"we show that MIC13 has a fundamental role in crista junction formation and that assembly of respiratory chain supercomplexes is independent of mitochondrial cristae shape.","explanation":"The authors' own conclusion, which contradicts the simplest reading of this entry's causal chain. Recorded as REFUTE against the link rather than omitted, because the chain from cristae collapse to combined respiratory deficiency is the entry's central claim and this is the strongest evidence against it."},{"reference":"PMID:27479602","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/27479602","reference_title":"Mic13 Is Essential for Formation of Crista Junctions in Mammalian Cells.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"MIC13 is also dispensable for assembly of respiratory chain complexes and for maintaining mitochondrial network morphology. Still, lack of MIC13 resulted in a moderate reduction of mitochondrial respiration.","explanation":"The measurement behind the negative result, including the moderate respiration decrement that did occur."}],"evidence_text":["We show that MIC13 is an inner membrane protein physically interacting with MIC60, a central subunit of the MICOS complex.","Using the CRISPR/Cas method we generated the first cell line deleted for MIC13.","MIC13 is required for the assembly of MIC10, MIC26, and MIC27 into the MICOS complex. However, it is not needed for the formation of the MIC60/MIC19/MIC25 subcomplex","These knockout cells show a complete loss of crista junctions demonstrating that MIC13 is strictly required for the formation of crista junctions.","we show that MIC13 has a fundamental role in crista junction formation and that assembly of respiratory chain supercomplexes is independent of mitochondrial cristae shape.","MIC13 is also dispensable for assembly of respiratory chain complexes and for maintaining mitochondrial network morphology. Still, lack of MIC13 resulted in a moderate reduction of mitochondrial respiration.","Establishes the molecular relationship the model is built to interrogate, which is what makes a MIC13 deletion informative about MICOS architecture.","Establishes the model as a clean deletion rather than a patient-derived system, so results in it are attributable to MIC13 loss alone.","Names both halves of the selectivity: which subcomplex fails and which is spared.","The direct measurement, in the model where the lesion is the only variable.","The authors' own conclusion, which contradicts the simplest reading of this entry's causal chain. Recorded as REFUTE against the link rather than omitted, because the chain from cristae collapse to combined respiratory deficiency is the entry's central claim and this is the strongest evidence against it.","The measurement behind the negative result, including the moderate respiration decrement that did occur."],"evidence_status":"Evidence recorded","metadata_completeness":40,"metadata_present":["Model category","NAMO class","Modeled mechanism","Evidence"],"metadata_missing":["Organism","Anatomy","Cell type","Cell source","Culture system","Publication"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Combined_Oxidative_Phosphorylation_Defect_Type_37.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Combined_Oxidative_Phosphorylation_Defect_Type_37.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Oxidative_Phosphorylation_Defect_Type_37.html#experimental-model-crispr-mic13-knockout-human-cell-line","source_anchor":"experimental-model-crispr-mic13-knockout-human-cell-line"},{"id":"model:kb/disorders/Auroneurodental_Syndrome.yaml:CRISPR NAA80 knockout HAP1 cells","name":"CRISPR NAA80 knockout HAP1 cells","description":"Two knockout clones were compared with control cells and reconstituted with wild-type or engineered catalytically inactive NAA80. The inactive construct carries W105F/R170Q/G173D/Y205F and is not the patient allele. Migration, protrusions, G/F-actin ratios and latrunculin recovery were measured.","notes":null,"context_id":"disorder:Auroneurodental_Syndrome","context_kind":"Disorder","disease_name":"Auroneurodental Syndrome","disease_synonyms":["NAA80-related syndrome","AURDENS"],"disease_term":{"id":"MONDO:0970998","label":"auroneurodental syndrome","display_label":"auroneurodental syndrome","url":"http://purl.obolibrary.org/obo/MONDO_0970998"},"experimental_model_type":"CELL_LINE","experimental_model_type_label":"Cell line","namo_type":"namo:CellLineModel","declared_namo_class_name":null,"namo_class_name":"CellLineModel","namo_class_label":"Cell Line Model","namo_description":"A model system based on immortalized cell lines that can be maintained in culture indefinitely. Examples: HepG2, A549, Caco-2, etc.","namo_docs_url":"https://monarch-initiative.github.io/namo/elements/CellLineModel/","namo_ontology_url":"https://w3id.org/monarch-initiative/namo/CellLineModel","namo_mapping_basis":"Safe mapping from DisMech category","namo_class_in_schema":true,"namo_schema_status":"Defined in NAMO schema used for this build","modality":"Cellular system","organism":{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},"organism_label":"Homo sapiens","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":null,"source_category":"Immortalized / cell line","culture_system":null,"publication":"PMID:29581253","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/29581253","mechanisms":[{"target":"Reduced Actin N-Terminal Acetylation","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Auroneurodental_Syndrome.html#pathophysiology-reduced-actin-n-terminal-acetylation","relationship":"MEASURES","relationship_label":"Measures","fidelity":"MODERATE","fidelity_label":"Moderate","description":"Proteomic analysis showed loss of beta/gamma-actin N-terminal acetylation.","limitations":"Complete knockout in a cell line, rather than the human hypomorphic allele or affected tissues.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[],"biological_processes":[],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Acetylated beta/gamma-actin","description":null,"target":"Reduced Actin N-Terminal Acetylation","direction":"ABOLISHED","interpretation":"Proteomic analysis showed loss of beta/gamma-actin N-terminal acetylation.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:29581253","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/29581253","reference_title":"NAA80 is actin's N-terminal acetyltransferase and regulates cytoskeleton assembly and cell motility.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Furthermore, both actin isoforms were 100% and 0% Nt-acetylated in control and NAA80 KO1 cells, respectively.","explanation":"Proteomic analysis showed loss of beta/gamma-actin N-terminal acetylation."}],"notes":null}],"evidence":[{"reference":"PMID:29581253","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/29581253","reference_title":"NAA80 is actin's N-terminal acetyltransferase and regulates cytoskeleton assembly and cell motility.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Furthermore, both actin isoforms were 100% and 0% Nt-acetylated in control and NAA80 KO1 cells, respectively.","explanation":"Proteomic analysis showed loss of beta/gamma-actin N-terminal acetylation."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Auroneurodental_Syndrome","model_node_id":"model:kb/disorders/Auroneurodental_Syndrome.yaml:CRISPR NAA80 knockout HAP1 cells","focus_node_id":"node:disorder%3AAuroneurodental_Syndrome:pathophysiology:Reduced%20Actin%20N-Terminal%20Acetylation","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Auroneurodental_Syndrome.html#pathograph","nodes":[{"id":"model:kb/disorders/Auroneurodental_Syndrome.yaml:CRISPR NAA80 knockout HAP1 cells","kind":"experimental_model","kind_label":"NAM model","label":"CRISPR NAA80 knockout HAP1 cells","description":"Two knockout clones were compared with control cells and reconstituted with wild-type or engineered catalytically inactive NAA80. The inactive construct carries W105F/R170Q/G173D/Y205F and is not the patient allele. Migration, protrusions, G/F-actin ratios and latrunculin recovery were measured.","url":"https://dismech.monarchinitiative.org/pages/disorders/Auroneurodental_Syndrome.html#experimental-model-crispr-naa80-knockout-hap1-cells","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAuroneurodental_Syndrome:pathophysiology:Reduced%20Actin%20N-Terminal%20Acetylation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced Actin N-Terminal Acetylation","description":"N-terminal acetylation of cytoplasmic beta- and gamma-actin is reduced in the sampled patient cells, with 25–65% unacetylated depending on cell type and actin isoform. Residual acetylation distinguishes this human allele from a complete knockout. Acetylation in human inner ear, brain and muscle was not measured.","url":"https://dismech.monarchinitiative.org/pages/disorders/Auroneurodental_Syndrome.html#pathophysiology-reduced-actin-n-terminal-acetylation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAuroneurodental_Syndrome:pathophysiology:Increased%20Cell%20Migration","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Increased Cell Migration","description":"Fibroblasts and PBMCs from affected individuals migrate more in chemotactic assays. Wild-type NAA80 expression rescues fibroblast migration; HAP1 knockout experiments also show increased directed and random migration. Migration was not measured in the patients’ developing neurons or craniofacial tissues.","url":"https://dismech.monarchinitiative.org/pages/disorders/Auroneurodental_Syndrome.html#pathophysiology-increased-cell-migration","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAuroneurodental_Syndrome:pathophysiology:Increased%20Filamentous%20Actin%20Content","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Increased Filamentous Actin Content","description":"Patient fibroblasts and PBMCs have increased phalloidin-stained filamentous actin; wild-type NAA80 expression normalizes the fibroblast signal. HAP1 knockout cells show a lower globular-to-filamentous actin ratio. These abundance measurements do not show an increased instantaneous polymerization rate.","url":"https://dismech.monarchinitiative.org/pages/disorders/Auroneurodental_Syndrome.html#pathophysiology-increased-filamentous-actin-content","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAuroneurodental_Syndrome:pathophysiology:Increased%20Filopodia%20Formation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Increased Filopodia Formation","description":"Fibroblasts from the elder brother have increased filopodia counts that normalize after wild-type NAA80 expression. Knockout HAP1 cells independently show more and longer filopodia-like protrusions. A direct causal route from this cultured-cell phenotype to human neural or craniofacial malformations has not been demonstrated.","url":"https://dismech.monarchinitiative.org/pages/disorders/Auroneurodental_Syndrome.html#pathophysiology-increased-filopodia-formation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAuroneurodental_Syndrome:pathophysiology:Reduced%20Inner-Ear%20Hair-Cell%20Bundles","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced Inner-Ear Hair-Cell Bundles","description":"Transient naa80-targeted F0 zebrafish larvae have fewer lateral-crista hair-cell bundles. 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Hypobetalipoproteinemias.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"we developed two knock-out cell models of FHBL-SD1 and FHBL-SD3 using the CRISPR/Cas9 technique in Caco-2/TC7 cells","explanation":"Describes the construction of the model."},{"reference":"PMID:36771214","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/36771214","reference_title":"Validation of Knock-Out Caco-2 TC7 Cells as Models of Enterocytes of Patients with Familial Genetic Hypobetalipoproteinemias.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"MTTP silencing led to a more severe phenotype than SAR1B silencing, which is consistent with clinical observations.","explanation":"The model reproduces the clinical severity ordering between abetalipoproteinemia and CRD, which supports its fidelity for this node."},{"reference":"PMID:36771214","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/36771214","reference_title":"Validation of Knock-Out Caco-2 TC7 Cells as Models of 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Residual translation from the c.2T>C start-loss allele and nonsense-mediated-decay escape of p.Glu208* remain predictions.","url":"https://dismech.monarchinitiative.org/pages/disorders/CEDNIK_Syndrome.html#pathophysiology-snap29-loss-of-function","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ACEDNIK_Syndrome:pathophysiology:Abnormal%20Cerebral%20Myelination","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Abnormal Cerebral Myelination","description":"Hypomyelination is documented in four of six patients in the 2021 series. One patient had initially normal myelination followed by marked loss, showing that abnormal white matter can reflect progressive loss as well as impaired development. 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Human neuroepithelial stem-cell knockdown also causes spindle abnormalities and micronuclei. These models identify a candidate developmental mechanism; they do not establish its contribution to each human brain malformation.","url":"https://dismech.monarchinitiative.org/pages/disorders/CEDNIK_Syndrome.html#pathophysiology-defective-mitotic-chromosome-segregation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ACEDNIK_Syndrome:pathophysiology:Endoplasmic%20Reticulum%20Stress","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Endoplasmic Reticulum Stress","description":"Primary fibroblasts from Snap29-null mice show increased CHOP. 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Transferrin uptake, VSVG secretory transport and cholera-toxin-B retrograde transport were preserved in these assays.","url":"https://dismech.monarchinitiative.org/pages/disorders/CEDNIK_Syndrome.html#pathophysiology-impaired-endocytic-recycling","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ACEDNIK_Syndrome:pathophysiology:Impaired%20Swallowing","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Swallowing","description":"Swallowing dysfunction with thin-liquid aspiration was documented in a confirmed patient. 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measurement."}],"notes":null}],"evidence":[{"reference":"PMID:30127391","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30127391","reference_title":"Genetically engineered human cortical spheroid models of tuberous sclerosis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Using heterozygous TSC2 hPSCs with a conditional mutation in the functional allele, we show that mosaic biallelic inactivation during neural progenitor expansion is necessary for the formation of dysplastic cells and increased glia production in three-dimensional cortical spheroids. Our findings provide support for the second-hit model of cortical tuber formation","explanation":"A human model in which the second hit is necessary for the dysplastic phenotype directly tests the node."},{"reference":"PMID:30127391","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30127391","reference_title":"Genetically engineered human cortical spheroid models of tuberous sclerosis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"mosaic biallelic inactivation during neural progenitor expansion is necessary for the formation of dysplastic cells and increased glia production in three-dimensional cortical spheroids","explanation":"Reports the dysplasia measurement."},{"reference":"PMID:30127391","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30127391","reference_title":"Genetically engineered human cortical spheroid models of tuberous sclerosis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"increased glia production in three-dimensional cortical spheroids","explanation":"Reports the glia measurement."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Tuberous_Sclerosis_Complex","model_node_id":"model:kb/disorders/Tuberous_Sclerosis_Complex.yaml:CRISPR-engineered TSC2 conditional-biallelic human cortical spheroids","focus_node_id":"node:disorder%3ATuberous_Sclerosis_Complex:pathophysiology:Somatic%20Second%20Hit%20at%20TSC%20Locus","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Tuberous_Sclerosis_Complex.html#pathograph","nodes":[{"id":"model:kb/disorders/Tuberous_Sclerosis_Complex.yaml:CRISPR-engineered TSC2 conditional-biallelic human cortical spheroids","kind":"experimental_model","kind_label":"NAM model","label":"CRISPR-engineered TSC2 conditional-biallelic human cortical spheroids","description":"Isogenic cortical spheroids in which the timing of biallelic TSC2 loss can be controlled. 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The two-hit model accounts for the focal nature of hamartomas (cortical tubers, angiomyolipomas, SEGAs, rhabdomyomas, LAM) despite a germline heterozygous mutation. Approximately 10-15% of clinically definite TSC cases have no germline pathogenic variant identified, with low-level somatic mosaicism postulated as the underlying mechanism. The requirement for a second hit is well established for the classic hamartomas but is not universal across lesion classes: mesenchymal tumorigenesis in the TSC2+/- mouse proceeds from haploinsufficiency alone and is HMGA2- rather than mTOR-dependent, with mTOR pathway activation detectable in only half of the corresponding human tumours.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Tuberous_Sclerosis_Complex.html#pathophysiology-somatic-second-hit-at-tsc-locus","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ATuberous_Sclerosis_Complex:pathophysiology:Constitutive%20mTORC1%20Hyperactivation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Constitutive mTORC1 Hyperactivation","description":"Loss of TSC1/TSC2 GAP activity allows persistent RHEB-GTP loading at the lysosomal membrane, leading to constitutive activation of mTORC1 kinase activity. Active mTORC1 phosphorylates downstream effectors (S6K1, 4E-BP1, ULK1, lipin-1, TFEB) that drive translation, anabolic biosynthesis, cell growth, and suppression of autophagy. mTORC1 signalling is constitutively active within all TSC-associated lesions and is the central, druggable pathobiological hub of the disease.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Tuberous_Sclerosis_Complex.html#pathophysiology-constitutive-mtorc1-hyperactivation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ATuberous_Sclerosis_Complex:pathophysiology:TSC1%2FTSC2%20Loss%20of%20Function%20%28Germline%20First%20Hit%29","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"TSC1/TSC2 Loss of Function (Germline First Hit)","description":"Heterozygous loss-of-function variants in TSC1 (hamartin) or TSC2 (tuberin) disrupt the TSC1/TSC2 protein complex, which normally functions as a GTPase-activating protein (GAP) for the small GTPase RHEB. The germline pathogenic variant constitutes the \"first hit\" in a Knudson two-hit model; by itself it produces haploinsufficiency but typical hamartomatous lesions require a somatic second hit at the TSC locus.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Tuberous_Sclerosis_Complex.html#pathophysiology-tsc1-tsc2-loss-of-function-germline-first-hit","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Tuberous_Sclerosis_Complex.yaml:CRISPR-engineered TSC2 conditional-biallelic human cortical spheroids","source_id":"model:kb/disorders/Tuberous_Sclerosis_Complex.yaml:CRISPR-engineered TSC2 conditional-biallelic human cortical spheroids","target_id":"node:disorder%3ATuberous_Sclerosis_Complex:pathophysiology:Somatic%20Second%20Hit%20at%20TSC%20Locus","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"The conditional allele lets biallelic TSC2 loss be triggered in a mosaic of neural progenitors, and only that second hit produces dysplastic cells and excess glia, which is the somatic second-hit node.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ATuberous_Sclerosis_Complex:2:0","source_id":"node:disorder%3ATuberous_Sclerosis_Complex:pathophysiology:Somatic%20Second%20Hit%20at%20TSC%20Locus","target_id":"node:disorder%3ATuberous_Sclerosis_Complex:pathophysiology:Constitutive%20mTORC1%20Hyperactivation","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Biallelic loss of TSC1/TSC2 in lesion cells removes GAP activity for RHEB and produces constitutive mTORC1 activation in the affected clone.\n","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ATuberous_Sclerosis_Complex:0:0","source_id":"node:disorder%3ATuberous_Sclerosis_Complex:pathophysiology:TSC1%2FTSC2%20Loss%20of%20Function%20%28Germline%20First%20Hit%29","target_id":"node:disorder%3ATuberous_Sclerosis_Complex:pathophysiology:Somatic%20Second%20Hit%20at%20TSC%20Locus","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"A second somatic hit at the wild-type TSC1 or TSC2 allele in lesion precursor cells is required for full TSC1/TSC2 complex inactivation and focal hamartomatous lesion growth. This explains the focal, mosaic-like distribution of cortical tubers, angiomyolipomas, SEGAs, and rhabdomyomas despite a constitutional germline mutation.\n","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0}]}},{"target":"Neuroglial Dysplasia and Cortical Network Disorganization","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Tuberous_Sclerosis_Complex.html#pathophysiology-neuroglial-dysplasia-and-cortical-network-disorganization","relationship":"PARTIALLY_RECAPITULATES","relationship_label":"Partially Recapitulates","fidelity":"MODERATE","fidelity_label":"Moderate","description":"Spheroids reproduce the dysmorphic cells and glial excess of a tuber but not cortical lamination, network activity or epileptogenesis.","limitations":"No layered cortex, no electrophysiological network readout and no seizure phenotype; the tuber is represented by its cellular composition only.","biological_scale":null,"anatomy":[{"id":"UBERON:0000955","label":"brain","display_label":"brain","url":"http://purl.obolibrary.org/obo/UBERON_0000955"}],"cell_types":[{"id":"CL:0000540","label":"neuron","display_label":"neuron","url":"http://purl.obolibrary.org/obo/CL_0000540"},{"id":"CL:0000127","label":"astrocyte","display_label":"astrocyte","url":"http://purl.obolibrary.org/obo/CL_0000127"}],"biological_processes":[{"id":"GO:0007399","label":"nervous system development","display_label":"nervous system development","url":"http://purl.obolibrary.org/obo/GO_0007399"},{"id":"GO:0030182","label":"neuron differentiation","display_label":"neuron differentiation","url":"http://purl.obolibrary.org/obo/GO_0030182"},{"id":"GO:0008283","label":"cell population proliferation","display_label":"cell population proliferation","url":"http://purl.obolibrary.org/obo/GO_0008283"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Dysplastic cells and glia in cortical spheroids","description":null,"target":"Neuroglial Dysplasia and Cortical Network Disorganization","direction":"INCREASED","interpretation":"Tuber-like cellular composition arises after the second hit.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:30127391","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30127391","reference_title":"Genetically engineered human cortical spheroid models of tuberous sclerosis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"the formation of dysplastic cells and increased glia production in three-dimensional cortical spheroids","explanation":"Reports the cellular composition measurement."}],"notes":null}],"evidence":[{"reference":"PMID:30127391","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30127391","reference_title":"Genetically engineered human cortical spheroid models of tuberous sclerosis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Hallmark pathologies of TSC are cortical tubers-regions of dysmorphic, disorganized neurons and glia in the cortex that are linked to epileptogenesis. To determine the developmental origin of tuber cells, we established human cellular models of TSC","explanation":"The model is built to reproduce tuber cell composition, which is part of what this node describes."},{"reference":"PMID:30127391","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30127391","reference_title":"Genetically engineered human cortical spheroid models of tuberous sclerosis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"the formation of dysplastic cells and increased glia production in three-dimensional cortical spheroids","explanation":"Reports the cellular composition measurement."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Tuberous_Sclerosis_Complex","model_node_id":"model:kb/disorders/Tuberous_Sclerosis_Complex.yaml:CRISPR-engineered TSC2 conditional-biallelic human cortical spheroids","focus_node_id":"node:disorder%3ATuberous_Sclerosis_Complex:pathophysiology:Neuroglial%20Dysplasia%20and%20Cortical%20Network%20Disorganization","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Tuberous_Sclerosis_Complex.html#pathograph","nodes":[{"id":"model:kb/disorders/Tuberous_Sclerosis_Complex.yaml:CRISPR-engineered TSC2 conditional-biallelic human cortical spheroids","kind":"experimental_model","kind_label":"NAM model","label":"CRISPR-engineered TSC2 conditional-biallelic human cortical spheroids","description":"Isogenic cortical spheroids in which the timing of biallelic TSC2 loss can be controlled. 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These lesions and network abnormalities provide the pathophysiologic bridge from TSC1/TSC2 mutation to infantile spasms, drug-resistant focal seizures, and TSC-associated neuropsychiatric disorders (TAND).\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Tuberous_Sclerosis_Complex.html#pathophysiology-neuroglial-dysplasia-and-cortical-network-disorganization","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ATuberous_Sclerosis_Complex:phenotype:Anxiety","kind":"phenotype","kind_label":"Phenotype","label":"Anxiety","description":"Anxiety symptoms are a common psychiatric component of TAND, contributing to reduced quality of life.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Tuberous_Sclerosis_Complex.html#phenotype-anxiety","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ATuberous_Sclerosis_Complex:phenotype:Attention%20Deficit%20Hyperactivity%20Disorder","kind":"phenotype","kind_label":"Phenotype","label":"Attention Deficit Hyperactivity Disorder","description":"Attention deficits and hyperactivity occur as part of the TSC-associated neuropsychiatric disorders (TAND) spectrum.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Tuberous_Sclerosis_Complex.html#phenotype-attention-deficit-hyperactivity-disorder","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ATuberous_Sclerosis_Complex:phenotype:Autism%20Spectrum%20Disorder","kind":"phenotype","kind_label":"Phenotype","label":"Autism Spectrum Disorder","description":"Autism spectrum disorder is present in approximately 40-50% of TSC patients and is associated with early-onset seizures and cortical tuber burden; TAND collectively affects ~90% of TSC patients across the lifespan.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Tuberous_Sclerosis_Complex.html#phenotype-autism-spectrum-disorder","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ATuberous_Sclerosis_Complex:phenotype:Cortical%20Tubers","kind":"phenotype","kind_label":"Phenotype","label":"Cortical Tubers","description":"Cortical tubers are hamartomatous lesions at the gray-white matter interface containing abnormal glial and neural cells (including dysmorphic giant neurons). 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Our findings provide support for the second-hit model of cortical tuber formation","explanation":"A human model in which the second hit is necessary for the dysplastic phenotype directly tests the node."},{"reference":"PMID:30127391","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30127391","reference_title":"Genetically engineered human cortical spheroid models of tuberous sclerosis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"mosaic biallelic inactivation during neural progenitor expansion is necessary for the formation of dysplastic cells and increased glia production in three-dimensional cortical spheroids","explanation":"Reports the dysplasia measurement."},{"reference":"PMID:30127391","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30127391","reference_title":"Genetically engineered human cortical spheroid models of tuberous sclerosis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"increased glia production in three-dimensional cortical spheroids","explanation":"Reports the glia measurement."},{"reference":"PMID:30127391","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30127391","reference_title":"Genetically engineered human cortical spheroid models of tuberous sclerosis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Hallmark pathologies of TSC are cortical tubers-regions of dysmorphic, disorganized neurons and glia in the cortex that are linked to epileptogenesis. 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Examples: HepG2, A549, Caco-2, etc.","namo_docs_url":"https://monarch-initiative.github.io/namo/elements/CellLineModel/","namo_ontology_url":"https://w3id.org/monarch-initiative/namo/CellLineModel","namo_mapping_basis":"Safe mapping from DisMech category","namo_class_in_schema":true,"namo_schema_status":"Defined in NAMO schema used for this build","modality":"Cellular system","organism":{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},"organism_label":"Homo sapiens","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":null,"source_category":"Immortalized / cell line","culture_system":null,"publication":"PMID:35484149","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35484149","mechanisms":[{"target":"Impaired Retrieval of KDEL-Bearing Chaperones to the ER","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Immunodeficiency_128.html#pathophysiology-impaired-retrieval-of-kdel-bearing-chaperones-to-the-er","relationship":"RECAPITULATES","relationship_label":"Recapitulates","fidelity":"MODERATE","fidelity_label":"Moderate","description":"Deleting COPG1 reproduces the retrograde-trafficking defect, measured as KDEL signal redistributing onto the cis-Golgi.","limitations":"This is a complete null, not the patients' missense allele, and it is a HeLa or THP-1 cell rather than a lymphocyte. The patients' substitution leaves the subunit expressed and incorporated into the coat and disables one interaction, so a deletion may overstate the functional loss and may engage consequences the missense allele does not.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0006890","label":"retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum","display_label":"retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum","url":"http://purl.obolibrary.org/obo/GO_0006890"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[],"evidence":[{"reference":"PMID:35484149","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/35484149","reference_title":"Deficiency in coatomer complex I causes aberrant activation of STING signalling.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"These results indicate that genetic deletion of COPA, COPG1 or COPD results in impaired retrograde trafficking","explanation":"Reports the retrograde-trafficking defect measured in COPG1-deleted cells."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Immunodeficiency_128","model_node_id":"model:kb/disorders/Immunodeficiency_128.yaml:CRISPR/Cas9 COPG1-deficient HeLa and THP-1 cell lines","focus_node_id":"node:disorder%3AImmunodeficiency_128:pathophysiology:Impaired%20Retrieval%20of%20KDEL-Bearing%20Chaperones%20to%20the%20ER","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Immunodeficiency_128.html#pathograph","nodes":[{"id":"model:kb/disorders/Immunodeficiency_128.yaml:CRISPR/Cas9 COPG1-deficient HeLa and THP-1 cell lines","kind":"experimental_model","kind_label":"NAM model","label":"CRISPR/Cas9 COPG1-deficient HeLa and THP-1 cell lines","description":"Complete deletion of COPG1 in human cell lines, used to ask whether the retrograde-transport lesion of COPA syndrome generalises across COPI subunits. It does: COPG1-null cells show the same shift of KDEL-tagged chaperones towards the Golgi, and they activate cGAS/STING and type I interferon signalling spontaneously.","url":"https://dismech.monarchinitiative.org/pages/disorders/Immunodeficiency_128.html#experimental-model-crispr-cas9-copg1-deficient-hela-and-thp-1-cell-lines","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AImmunodeficiency_128:pathophysiology:Impaired%20Retrieval%20of%20KDEL-Bearing%20Chaperones%20to%20the%20ER","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Retrieval of KDEL-Bearing Chaperones to the ER","description":"KDEL-bearing ER chaperones that have escaped to the Golgi are not returned, depleting the ER of the folding capacity it needs when secretory demand rises.","url":"https://dismech.monarchinitiative.org/pages/disorders/Immunodeficiency_128.html#pathophysiology-impaired-retrieval-of-kdel-bearing-chaperones-to-the-er","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AImmunodeficiency_128:pathophysiology:Disrupted%20COPI%20Binding%20to%20the%20KDEL%20Receptor","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Disrupted COPI Binding to the KDEL Receptor","description":"The mutant coatomer no longer binds the KDEL receptor, the cargo receptor that captures ER-resident chaperones escaped to the Golgi. COPI itself is the complex that mediates retrograde traffic from Golgi to endoplasmic reticulum, so losing the receptor interaction removes the link between coat and cargo rather than abolishing the coat.","url":"https://dismech.monarchinitiative.org/pages/disorders/Immunodeficiency_128.html#pathophysiology-disrupted-copi-binding-to-the-kdel-receptor","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AImmunodeficiency_128:pathophysiology:Endoplasmic%20Reticulum%20Stress%20in%20Activated%20Lymphocytes","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Endoplasmic Reticulum Stress in Activated Lymphocytes","description":"Activated T and B cells accumulate ER stress. This is the point at which a housekeeping trafficking defect becomes an immune defect, because it is activation, not the resting state, that raises the folding load.","url":"https://dismech.monarchinitiative.org/pages/disorders/Immunodeficiency_128.html#pathophysiology-endoplasmic-reticulum-stress-in-activated-lymphocytes","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Immunodeficiency_128.yaml:CRISPR/Cas9 COPG1-deficient HeLa and THP-1 cell lines","source_id":"model:kb/disorders/Immunodeficiency_128.yaml:CRISPR/Cas9 COPG1-deficient HeLa and THP-1 cell lines","target_id":"node:disorder%3AImmunodeficiency_128:pathophysiology:Impaired%20Retrieval%20of%20KDEL-Bearing%20Chaperones%20to%20the%20ER","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"Deleting COPG1 reproduces the retrograde-trafficking defect, measured as KDEL signal redistributing onto the 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retrieval.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AImmunodeficiency_128:2:0","source_id":"node:disorder%3AImmunodeficiency_128:pathophysiology:Impaired%20Retrieval%20of%20KDEL-Bearing%20Chaperones%20to%20the%20ER","target_id":"node:disorder%3AImmunodeficiency_128:pathophysiology:Endoplasmic%20Reticulum%20Stress%20in%20Activated%20Lymphocytes","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"The knock-in mouse shows that the retrieval defect is expressed as ER stress specifically in lymphocytes that have been activated, that is, in cells whose secretory load has just increased.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1}]}}],"mechanism_names":["Impaired Retrieval of KDEL-Bearing Chaperones to the ER"],"relationships":["Recapitulates"],"fidelities":["Moderate"],"biological_scales":["Cellular"],"system_context_sources":["Linked mechanism biological scale"],"modeled_system_labels":["Cellular"],"biological_process_terms":[{"id":"GO:0006890","label":"retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum","display_label":"retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum","url":"http://purl.obolibrary.org/obo/GO_0006890"}],"biological_processes":["retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum"],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":[],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:35484149","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/35484149","reference_title":"Deficiency in coatomer complex I causes aberrant activation of STING signalling.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"only deletion of COPG1 resulted in spontaneous phosphorylation of STAT1 and inflammatory gene transcription","explanation":"Reports that COPG1 loss, unlike COPG2 loss, drives spontaneous inflammatory signalling, which is the finding that makes this model relevant beyond the trafficking defect."},{"reference":"PMID:35484149","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/35484149","reference_title":"Deficiency in coatomer complex I causes aberrant activation of STING signalling.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"These results indicate that genetic deletion of COPA, COPG1 or COPD results in impaired retrograde trafficking","explanation":"Reports the retrograde-trafficking defect measured in COPG1-deleted cells."}],"evidence_text":["only deletion of COPG1 resulted in spontaneous phosphorylation of STAT1 and inflammatory gene transcription","These results indicate that genetic deletion of COPA, COPG1 or COPD results in impaired retrograde trafficking","Reports that COPG1 loss, unlike COPG2 loss, drives spontaneous inflammatory signalling, which is the finding that makes this model relevant beyond the trafficking defect.","Reports the retrograde-trafficking defect measured in COPG1-deleted cells."],"evidence_status":"Evidence recorded","metadata_completeness":60,"metadata_present":["Model category","NAMO class","Organism","Modeled mechanism","Publication","Evidence"],"metadata_missing":["Anatomy","Cell type","Cell source","Culture system"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Immunodeficiency_128.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Immunodeficiency_128.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Immunodeficiency_128.html#experimental-model-crispr-cas9-copg1-deficient-hela-and-thp-1-cell-lines","source_anchor":"experimental-model-crispr-cas9-copg1-deficient-hela-and-thp-1-cell-lines"},{"id":"model:kb/disorders/Bone_Marrow_Failure_Syndrome_6.yaml:CRISPR/Cas9 MDM4-deleted healthy-donor HSPCs","name":"CRISPR/Cas9 MDM4-deleted healthy-donor HSPCs","description":"MDM4 deleted in hematopoietic stem and progenitor cells from healthy donors, producing MDM4-haploinsufficient cells on an otherwise normal genetic background. This is the cleanest available test of dosage, since it isolates MDM4 copy number from patient genetic background.\n","notes":null,"context_id":"disorder:Bone_Marrow_Failure_Syndrome_6","context_kind":"Disorder","disease_name":"Bone Marrow Failure Syndrome 6","disease_synonyms":["BMFS6","MDM4 haploinsufficiency","MDM4 deficiency"],"disease_term":{"id":"MONDO:0030015","label":"bone marrow failure syndrome 6","display_label":"bone marrow failure syndrome 6","url":"http://purl.obolibrary.org/obo/MONDO_0030015"},"experimental_model_type":"PRIMARY_CELL_CULTURE","experimental_model_type_label":"Primary-cell culture","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[{"id":"CL:0000037","label":"hematopoietic stem cell","display_label":"hematopoietic stem cell","url":"http://purl.obolibrary.org/obo/CL_0000037"}],"linked_cell_type_labels":["hematopoietic stem cell"],"cell_types":[{"id":"CL:0000037","label":"hematopoietic stem cell","display_label":"hematopoietic stem cell","url":"http://purl.obolibrary.org/obo/CL_0000037"}],"cell_type_labels":["hematopoietic stem cell"],"conditions":[],"cell_source":null,"source_category":"Primary / biopsy-derived","culture_system":null,"publication":"PMID:41758987","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41758987","mechanisms":[{"target":"p53 Pathway Hyperactivation in Hematopoietic Stem and Progenitor Cells","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Bone_Marrow_Failure_Syndrome_6.html#pathophysiology-p53-pathway-hyperactivation-in-hematopoietic-stem-and-progenitor-cells","relationship":"RECAPITULATES","relationship_label":"Recapitulates","fidelity":"HIGH","fidelity_label":"High","description":"Human primary HSPCs with engineered MDM4 haploinsufficiency reproduce the p53 hyperactivity and the functional haematopoietic deficit.\n","limitations":"Engineered deletion is not the patient allelic spectrum: four of the six patient alleles are truncating, but two are missense, and a missense allele may retain partial function or act differently from a clean deletion. Engraftment is scored in immunodeficient mice, so the readout is a xenograft niche rather than a human marrow.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[{"id":"CL:0000037","label":"hematopoietic stem cell","display_label":"hematopoietic stem cell","url":"http://purl.obolibrary.org/obo/CL_0000037"}],"biological_processes":[{"id":"GO:0072331","label":"signal transduction by p53 class mediator","display_label":"signal transduction by p53 class mediator","url":"http://purl.obolibrary.org/obo/GO_0072331"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"p53 transcriptional activity","description":null,"target":"p53 Pathway Hyperactivation in Hematopoietic Stem and Progenitor Cells","direction":"INCREASED","interpretation":"Direct readout of the released p53 brake.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:41758987","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41758987","reference_title":"MDM4 haploinsufficiency leads to p53-mediated bone marrow failure.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The resulting MDM4-haploinsufficient HSPCs exhibited increased p53 activity, impaired colony-forming capacity, and reduced engraftment potential in immunodeficient mice.","explanation":"Reports increased p53 activity in the edited HSPCs."}],"notes":null},{"name":"Colony-forming capacity","description":null,"target":"p53 Pathway Hyperactivation in Hematopoietic Stem and Progenitor Cells","direction":"DECREASED","interpretation":"Functional cost of p53 hyperactivity to progenitor proliferation.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:41758987","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41758987","reference_title":"MDM4 haploinsufficiency leads to p53-mediated bone marrow failure.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The resulting MDM4-haploinsufficient HSPCs exhibited increased p53 activity, impaired colony-forming capacity, and reduced engraftment potential in immunodeficient mice.","explanation":"Reports impaired colony formation in the edited HSPCs."}],"notes":null}],"evidence":[{"reference":"PMID:41758987","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41758987","reference_title":"MDM4 haploinsufficiency leads to p53-mediated bone marrow failure.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The resulting MDM4-haploinsufficient HSPCs exhibited increased p53 activity, impaired colony-forming capacity, and reduced engraftment potential in immunodeficient mice.","explanation":"Reports increased p53 activity in the edited HSPCs."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Bone_Marrow_Failure_Syndrome_6","model_node_id":"model:kb/disorders/Bone_Marrow_Failure_Syndrome_6.yaml:CRISPR/Cas9 MDM4-deleted healthy-donor HSPCs","focus_node_id":"node:disorder%3ABone_Marrow_Failure_Syndrome_6:pathophysiology:p53%20Pathway%20Hyperactivation%20in%20Hematopoietic%20Stem%20and%20Progenitor%20Cells","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Bone_Marrow_Failure_Syndrome_6.html#pathograph","nodes":[{"id":"model:kb/disorders/Bone_Marrow_Failure_Syndrome_6.yaml:CRISPR/Cas9 MDM4-deleted healthy-donor HSPCs","kind":"experimental_model","kind_label":"NAM model","label":"CRISPR/Cas9 MDM4-deleted healthy-donor HSPCs","description":"MDM4 deleted in hematopoietic stem and progenitor cells from healthy donors, producing MDM4-haploinsufficient cells on an otherwise normal genetic background. This is the cleanest available test of dosage, since it isolates MDM4 copy number from patient genetic background.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Bone_Marrow_Failure_Syndrome_6.html#experimental-model-crispr-cas9-mdm4-deleted-healthy-donor-hspcs","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ABone_Marrow_Failure_Syndrome_6:pathophysiology:p53%20Pathway%20Hyperactivation%20in%20Hematopoietic%20Stem%20and%20Progenitor%20Cells","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"p53 Pathway Hyperactivation in Hematopoietic Stem and Progenitor Cells","description":"The central node. MDM4-haploinsufficient HSPCs show increased p53 activity; MDM4-mutant iPSCs show the same, read out as elevated p21 expression; and transcriptome analysis of iPSC-derived haematopoietic cells shows upregulation of the p53 pathway. The authors' summary conclusion is that MDM4 deficiency is a TP53-activating syndrome.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Bone_Marrow_Failure_Syndrome_6.html#pathophysiology-p53-pathway-hyperactivation-in-hematopoietic-stem-and-progenitor-cells","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ABone_Marrow_Failure_Syndrome_6:pathophysiology:Impaired%20HSPC%20Self-Renewal%20and%20Multilineage%20Output","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired HSPC Self-Renewal and Multilineage Output","description":"The functional cost of p53 hyperactivity, measured three ways: impaired colony-forming capacity, reduced engraftment potential in immunodeficient mice, and significantly reduced erythroid and myeloid cell yield from MDM4-mutant iPSCs. The lesion is on proliferation and differentiation capacity rather than on a single lineage, which is what makes the clinical picture a trilineage marrow failure rather than a single cytopenia.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Bone_Marrow_Failure_Syndrome_6.html#pathophysiology-impaired-hspc-self-renewal-and-multilineage-output","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ABone_Marrow_Failure_Syndrome_6:pathophysiology:Loss%20of%20MDM4-Mediated%20p53%20Restraint","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Loss of MDM4-Mediated p53 Restraint","description":"MDM4's normal job is to hold p53 down. Complementation studies establish that this function needs two distinct parts of the protein - the p53-binding domain and the RING-finger domain - so a variant disabling either one is sufficient, which is consistent with the mixed null and missense allelic spectrum.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Bone_Marrow_Failure_Syndrome_6.html#pathophysiology-loss-of-mdm4-mediated-p53-restraint","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ABone_Marrow_Failure_Syndrome_6:pathophysiology:Somatic%20TP53%20Loss-of-Function%20as%20Maladaptive%20Clonal%20Rescue","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Somatic TP53 Loss-of-Function as Maladaptive Clonal Rescue","description":"One patient who progressed to MDS acquired somatic loss-of-function TP53 mutations. The natural reading, and the one the source gives, is rescue: a clone that inactivates p53 escapes the growth disadvantage the germline MDM4 lesion imposes, and outcompetes its neighbours. It is maladaptive because the escape route runs through the loss of p53 tumour suppression, which is the classic substrate for progression to MDS and leukaemia. This is the inverse of the usual two-hit picture - the somatic event relieves the germline mechanism rather than compounding it.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Bone_Marrow_Failure_Syndrome_6.html#pathophysiology-somatic-tp53-loss-of-function-as-maladaptive-clonal-rescue","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ABone_Marrow_Failure_Syndrome_6:pathophysiology:Telomere%20Shortening","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Telomere Shortening","description":"Germline activation of the p53 pathway shortens telomeres. This is a human finding before it is a mouse one: the founding family had short telomeres alongside marrow hypocellularity, and the p.T454M knock-in mouse then reproduced increased p53 activity and decreased telomere length together with bone marrow failure. The direction of causation matters - the authors' conclusion is that germline p53-pathway activation may *cause* telomere dysfunction, which inverts the usual reading in which short telomeres are the primary lesion and p53 the downstream sensor.\nConformance is declared against the attrition node of `telomere_attrition` rather than against its DNA-damage/senescence node, because what is documented in BMFS6 is the shortening itself; the senescence step is inferred from the module, not measured in these patients.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Bone_Marrow_Failure_Syndrome_6.html#pathophysiology-telomere-shortening","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Bone_Marrow_Failure_Syndrome_6.yaml:CRISPR/Cas9 MDM4-deleted 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This relocates the syndromic deafness lesion to a leaky hemichannel in the supporting-cell network rather than to loss of potassium recycling, the account for the recessive nonsyndromic form.","url":"https://dismech.monarchinitiative.org/pages/disorders/Keratitis-Ichthyosis-Deafness_Syndrome.html#pathophysiology-cochlear-supporting-cell-hemichannel-hyperactivity","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3AKeratitis-Ichthyosis-Deafness_Syndrome:pathophysiology:Corneal%20Epithelial%20Gap%20Junction%20Dysfunction","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Corneal Epithelial Gap Junction Dysfunction","description":"Gap-junction communication in the human corneal epithelium is carried by Cx26, Cx30, Cx31.1 and Cx43. 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In contrast, in the p.R120W fibroblasts, no evidence of oxidative stress was observed (Fig. 4).","explanation":"MitoSOX, thiol and antioxidant readouts support oxidative stress in C240Y-family fibroblasts, whereas R120W-family cells did not show the same response."}],"notes":null}],"evidence":[{"reference":"url:https://univ-angers.hal.science/hal-02388209v1/document","reference_url":null,"reference_title":"https://univ-angers.hal.science/hal-02388209v1/document","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Using a fluorescent probe specific for superoxide a nions (MitoSOX TM ), we identified a 40% enhancement of fluorescence intensity in p.C240Y fi broblasts compared to controls (Fig. 4a and 4b, p=0.020). In addition, we observed a 50% decrease in thiol group level, which are the ROS targets, further supporting ROS overproduction (Fig. 4c, p=0.015). Moreover, the expression of manganese superoxide dismutase (MnSOD), a major mitochondrial antioxidant, was 53% higher in p.C240Y fibroblasts compared to c ontrols (Fig. 4d, p=0.045). In contrast, in the p.R120W fibroblasts, no evidence of oxidative stress was observed (Fig. 4).","explanation":"MitoSOX, thiol and antioxidant readouts support oxidative stress in C240Y-family fibroblasts, whereas R120W-family cells did not show the same response."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Autosomal_Dominant_Charcot-Marie-Tooth_Disease_Type_2K","model_node_id":"model:kb/disorders/Autosomal_Dominant_Charcot-Marie-Tooth_Disease_Type_2K.yaml:Dominant GDAP1 patient fibroblast redox and respiration study","focus_node_id":"node:disorder%3AAutosomal_Dominant_Charcot-Marie-Tooth_Disease_Type_2K:pathophysiology:Increased%20Mitochondrial%20Reactive%20Oxygen%20Species","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_dominant_Charcot-Marie-Tooth_disease_type_2K.html#pathograph","nodes":[{"id":"model:kb/disorders/Autosomal_Dominant_Charcot-Marie-Tooth_Disease_Type_2K.yaml:Dominant GDAP1 patient fibroblast redox and respiration study","kind":"experimental_model","kind_label":"NAM model","label":"Dominant GDAP1 patient fibroblast redox and respiration study","description":"Six patient lines came from two unrelated families: three C240Y and three R120W. 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No clinical benefit or universal GST-domain severity rule was demonstrated.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_dominant_Charcot-Marie-Tooth_disease_type_2K.html#experimental-model-dominant-gdap1-patient-fibroblast-redox-and-respiration-study","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAutosomal_Dominant_Charcot-Marie-Tooth_Disease_Type_2K:pathophysiology:Increased%20Mitochondrial%20Reactive%20Oxygen%20Species","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Increased Mitochondrial Reactive Oxygen Species","description":"Dominant-variant expression can increase mitochondrial ROS, and patient C240Y fibroblasts show increased MitoSOX signal with supporting oxidative-stress readouts. R120W patient fibroblasts in the same study did not show increased oxidative stress. Cell context and allele therefore matter.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_dominant_Charcot-Marie-Tooth_disease_type_2K.html#pathophysiology-increased-mitochondrial-reactive-oxygen-species","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAutosomal_Dominant_Charcot-Marie-Tooth_Disease_Type_2K:pathophysiology:Heterozygous%20GDAP1%20Pathogenic%20Variant","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Heterozygous GDAP1 Pathogenic Variant","description":"A dominant pathogenic GDAP1 allele perturbs peripheral nerve function. The experimentally measured consequences depend on the allele, construct and cell system; this node does not imply loss of the wild-type allele or a proven universal dominant-negative interaction.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_dominant_Charcot-Marie-Tooth_disease_type_2K.html#pathophysiology-heterozygous-gdap1-pathogenic-variant","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:2:model:kb/disorders/Autosomal_Dominant_Charcot-Marie-Tooth_Disease_Type_2K.yaml:Dominant GDAP1 patient fibroblast redox and respiration study","source_id":"model:kb/disorders/Autosomal_Dominant_Charcot-Marie-Tooth_Disease_Type_2K.yaml:Dominant GDAP1 patient fibroblast redox and respiration study","target_id":"node:disorder%3AAutosomal_Dominant_Charcot-Marie-Tooth_Disease_Type_2K:pathophysiology:Increased%20Mitochondrial%20Reactive%20Oxygen%20Species","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[2]","label":"Partially Recapitulates","directed":false,"relationship":"PARTIALLY_RECAPITULATES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"C240Y cells showed increased mitochondrial ROS-related fluorescence and additional oxidative-stress markers.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AAutosomal_Dominant_Charcot-Marie-Tooth_Disease_Type_2K:0:3","source_id":"node:disorder%3AAutosomal_Dominant_Charcot-Marie-Tooth_Disease_Type_2K:pathophysiology:Heterozygous%20GDAP1%20Pathogenic%20Variant","target_id":"node:disorder%3AAutosomal_Dominant_Charcot-Marie-Tooth_Disease_Type_2K:pathophysiology:Increased%20Mitochondrial%20Reactive%20Oxygen%20Species","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[3]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"C240Y patient fibroblasts show an oxidative-stress signal that was absent in the studied R120W fibroblasts; this is not a universal dominant-allele response.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1}]}},{"target":"Reduced Mitochondrial Complex I Activity","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_dominant_Charcot-Marie-Tooth_disease_type_2K.html#pathophysiology-reduced-mitochondrial-complex-i-activity","relationship":"RESCUES","relationship_label":"Rescues","fidelity":"LOW","fidelity_label":"Low","description":"Resveratrol increased pooled complex I activity in treated patient cultures.","limitations":"Per-allele results were trends; no established molecular mediator, neuronal rescue, human dose or clinical outcome.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[],"biological_processes":[],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Complex I activity after resveratrol","description":null,"target":"Reduced Mitochondrial Complex I Activity","direction":"INCREASED","interpretation":"Resveratrol increased pooled complex I activity in treated patient cultures.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"url:https://univ-angers.hal.science/hal-02388209v1/document","reference_url":null,"reference_title":"https://univ-angers.hal.science/hal-02388209v1/document","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Whereas treatment with 10 µM resv eratrol produced no significant modification of CI activity (data not shown), treat ment with 25µM resveratrol modulated CI activity in CMT2K fibroblasts with a trend towards the restoration of CI activity in both p.C240Y and p.R120W fibroblasts. We also assessed t he effect of resveratrol in alleviating mitochondrial dysfunction in cells carrying GDAP1 m utations independently of the location and mutation type in the perspective of potential f uture therapeutic studies on CMT2K patients. Combining both patient families showed a significant improvement of CI activity after resveratrol treatment (Fig. 5, p<0.05).","explanation":"The significant complex I effect comes from pooling the two families; allele-specific analyses were trends. Treatment was in culture, not patients."}],"notes":null}],"evidence":[{"reference":"url:https://univ-angers.hal.science/hal-02388209v1/document","reference_url":null,"reference_title":"https://univ-angers.hal.science/hal-02388209v1/document","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Whereas treatment with 10 µM resv eratrol produced no significant modification of CI activity (data not shown), treat ment with 25µM resveratrol modulated CI activity in CMT2K fibroblasts with a trend towards the restoration of CI activity in both p.C240Y and p.R120W fibroblasts. We also assessed t he effect of resveratrol in alleviating mitochondrial dysfunction in cells carrying GDAP1 m utations independently of the location and mutation type in the perspective of potential f uture therapeutic studies on CMT2K patients. Combining both patient families showed a significant improvement of CI activity after resveratrol treatment (Fig. 5, p<0.05).","explanation":"The significant complex I effect comes from pooling the two families; allele-specific analyses were trends. Treatment was in culture, not patients."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Autosomal_Dominant_Charcot-Marie-Tooth_Disease_Type_2K","model_node_id":"model:kb/disorders/Autosomal_Dominant_Charcot-Marie-Tooth_Disease_Type_2K.yaml:Dominant GDAP1 patient fibroblast redox and respiration study","focus_node_id":"node:disorder%3AAutosomal_Dominant_Charcot-Marie-Tooth_Disease_Type_2K:pathophysiology:Reduced%20Mitochondrial%20Complex%20I%20Activity","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_dominant_Charcot-Marie-Tooth_disease_type_2K.html#pathograph","nodes":[{"id":"model:kb/disorders/Autosomal_Dominant_Charcot-Marie-Tooth_Disease_Type_2K.yaml:Dominant GDAP1 patient fibroblast redox and respiration study","kind":"experimental_model","kind_label":"NAM model","label":"Dominant GDAP1 patient fibroblast redox and respiration study","description":"Six patient lines came from two unrelated families: three C240Y and three R120W. Available lines and controls varied by assay. Complex-I-substrate respiration and ATP synthesis were lower in both groups, but direct complex I enzyme and oxidative-stress abnormalities were clearest in C240Y. Complex I assembly and NDUFB8 abundance were preserved; SIRT1/NRF1 abundance decreased without a mediation experiment. Resveratrol treatment for 48 hours improved pooled complex I activity at 25 micromolar; 10 micromolar had no significant effect and 50 micromolar was antiproliferative. No clinical benefit or universal GST-domain severity rule was demonstrated.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_dominant_Charcot-Marie-Tooth_disease_type_2K.html#experimental-model-dominant-gdap1-patient-fibroblast-redox-and-respiration-study","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAutosomal_Dominant_Charcot-Marie-Tooth_Disease_Type_2K:pathophysiology:Reduced%20Mitochondrial%20Complex%20I%20Activity","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced Mitochondrial Complex I Activity","description":"Patient fibroblasts carrying C240Y show reduced complex I enzyme activity; the R120W reduction did not reach significance in the same study. Complex I subunit abundance and blue-native assembly were preserved. This is not evidence that all dominant GDAP1 alleles directly inhibit the respiratory complex.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_dominant_Charcot-Marie-Tooth_disease_type_2K.html#pathophysiology-reduced-mitochondrial-complex-i-activity","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAutosomal_Dominant_Charcot-Marie-Tooth_Disease_Type_2K:pathophysiology:Heterozygous%20GDAP1%20Pathogenic%20Variant","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Heterozygous GDAP1 Pathogenic Variant","description":"A dominant pathogenic GDAP1 allele perturbs peripheral nerve function. The experimentally measured consequences depend on the allele, construct and cell system; this node does not imply loss of the wild-type allele or a proven universal dominant-negative interaction.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_dominant_Charcot-Marie-Tooth_disease_type_2K.html#pathophysiology-heterozygous-gdap1-pathogenic-variant","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAutosomal_Dominant_Charcot-Marie-Tooth_Disease_Type_2K:pathophysiology:Reduced%20Complex%20I-Linked%20ATP%20Synthesis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced Complex I-Linked ATP Synthesis","description":"Complex-I-substrate-driven ATP synthesis is reduced in permeabilized C240Y and R120W fibroblasts. This substrate-specific flux measurement does not establish universal cellular ATP depletion or bioenergetic failure in dominant CMT2K neurons.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_dominant_Charcot-Marie-Tooth_disease_type_2K.html#pathophysiology-reduced-complex-i-linked-atp-synthesis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:3:model:kb/disorders/Autosomal_Dominant_Charcot-Marie-Tooth_Disease_Type_2K.yaml:Dominant GDAP1 patient fibroblast redox and respiration study","source_id":"model:kb/disorders/Autosomal_Dominant_Charcot-Marie-Tooth_Disease_Type_2K.yaml:Dominant GDAP1 patient fibroblast redox and respiration study","target_id":"node:disorder%3AAutosomal_Dominant_Charcot-Marie-Tooth_Disease_Type_2K:pathophysiology:Reduced%20Mitochondrial%20Complex%20I%20Activity","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[3]","label":"Rescues","directed":false,"relationship":"RESCUES","fidelity":"LOW","causal_link_type":null,"causal_link_type_label":null,"description":"Resveratrol increased pooled complex I activity in treated patient cultures.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AAutosomal_Dominant_Charcot-Marie-Tooth_Disease_Type_2K:0:4","source_id":"node:disorder%3AAutosomal_Dominant_Charcot-Marie-Tooth_Disease_Type_2K:pathophysiology:Heterozygous%20GDAP1%20Pathogenic%20Variant","target_id":"node:disorder%3AAutosomal_Dominant_Charcot-Marie-Tooth_Disease_Type_2K:pathophysiology:Reduced%20Mitochondrial%20Complex%20I%20Activity","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[4]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"Complex I activity is reduced in the studied C240Y fibroblasts; the R120W comparison was not statistically significant, and mediation of human neuropathy is unproven.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AAutosomal_Dominant_Charcot-Marie-Tooth_Disease_Type_2K:5:0","source_id":"node:disorder%3AAutosomal_Dominant_Charcot-Marie-Tooth_Disease_Type_2K:pathophysiology:Reduced%20Mitochondrial%20Complex%20I%20Activity","target_id":"node:disorder%3AAutosomal_Dominant_Charcot-Marie-Tooth_Disease_Type_2K:pathophysiology:Reduced%20Complex%20I-Linked%20ATP%20Synthesis","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[5].downstream[0]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"Complex I-linked respiratory impairment can limit substrate-driven ATP synthesis, although the direct enzyme assay and respiration assay have different significance patterns across the two alleles.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":2}]}}],"mechanism_names":["Reduced Mitochondrial Complex I Activity","Reduced Complex I-Linked ATP Synthesis","Increased Mitochondrial Reactive Oxygen Species"],"relationships":["Partially Recapitulates","Rescues"],"fidelities":["Moderate","Low"],"biological_scales":["Molecular","Cellular"],"system_context_sources":["Linked mechanism biological scale"],"modeled_system_labels":["Molecular","Cellular"],"biological_process_terms":[],"biological_processes":[],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":["Complex I enzymatic activity","Complex I-linked ATP synthesis","MitoSOX fluorescence","Complex I activity after resveratrol"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"url:https://univ-angers.hal.science/hal-02388209v1/document","reference_url":null,"reference_title":"https://univ-angers.hal.science/hal-02388209v1/document","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"CI enzymatic activity was about 50% lower in the p. C240Y fibroblasts compared to controls (Fig. 1a, p=0.01), while only reduced by 30% in the p.R120W fi broblasts (Fig. 1a, p=0.09).","explanation":"The enzyme-activity reduction was significant for C240Y but not R120W in two-family fibroblast comparisons."},{"reference":"url:https://univ-angers.hal.science/hal-02388209v1/document","reference_url":null,"reference_title":"https://univ-angers.hal.science/hal-02388209v1/document","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Measurements of mitochondrial oxygen consumption re vealed that using CI malate-pyruvate (MP) substrates, the respiratory rate (Fig. 1b) and the corresponding ATP production (Fig. 1c) were significantly lower in both mutant cell lines, compared to controls (40%, p<0.05 in both measurements).","explanation":"Permeabilized fibroblasts from both families had lower complex-I-substrate respiration and ATP synthesis under the experimental conditions."},{"reference":"url:https://univ-angers.hal.science/hal-02388209v1/document","reference_url":null,"reference_title":"https://univ-angers.hal.science/hal-02388209v1/document","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Using a fluorescent probe specific for superoxide a nions (MitoSOX TM ), we identified a 40% enhancement of fluorescence intensity in p.C240Y fi broblasts compared to controls (Fig. 4a and 4b, p=0.020). In addition, we observed a 50% decrease in thiol group level, which are the ROS targets, further supporting ROS overproduction (Fig. 4c, p=0.015). Moreover, the expression of manganese superoxide dismutase (MnSOD), a major mitochondrial antioxidant, was 53% higher in p.C240Y fibroblasts compared to c ontrols (Fig. 4d, p=0.045). In contrast, in the p.R120W fibroblasts, no evidence of oxidative stress was observed (Fig. 4).","explanation":"MitoSOX, thiol and antioxidant readouts support oxidative stress in C240Y-family fibroblasts, whereas R120W-family cells did not show the same response."},{"reference":"url:https://univ-angers.hal.science/hal-02388209v1/document","reference_url":null,"reference_title":"https://univ-angers.hal.science/hal-02388209v1/document","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Whereas treatment with 10 µM resv eratrol produced no significant modification of CI activity (data not shown), treat ment with 25µM resveratrol modulated CI activity in CMT2K fibroblasts with a trend towards the restoration of CI activity in both p.C240Y and p.R120W fibroblasts. We also assessed t he effect of resveratrol in alleviating mitochondrial dysfunction in cells carrying GDAP1 m utations independently of the location and mutation type in the perspective of potential f uture therapeutic studies on CMT2K patients. Combining both patient families showed a significant improvement of CI activity after resveratrol treatment (Fig. 5, p<0.05).","explanation":"The significant complex I effect comes from pooling the two families; allele-specific analyses were trends. Treatment was in culture, not patients."}],"evidence_text":["CI enzymatic activity was about 50% lower in the p. C240Y fibroblasts compared to controls (Fig. 1a, p=0.01), while only reduced by 30% in the p.R120W fi broblasts (Fig. 1a, p=0.09).","Measurements of mitochondrial oxygen consumption re vealed that using CI malate-pyruvate (MP) substrates, the respiratory rate (Fig. 1b) and the corresponding ATP production (Fig. 1c) were significantly lower in both mutant cell lines, compared to controls (40%, p<0.05 in both measurements).","Using a fluorescent probe specific for superoxide a nions (MitoSOX TM ), we identified a 40% enhancement of fluorescence intensity in p.C240Y fi broblasts compared to controls (Fig. 4a and 4b, p=0.020). In addition, we observed a 50% decrease in thiol group level, which are the ROS targets, further supporting ROS overproduction (Fig. 4c, p=0.015). Moreover, the expression of manganese superoxide dismutase (MnSOD), a major mitochondrial antioxidant, was 53% higher in p.C240Y fibroblasts compared to c ontrols (Fig. 4d, p=0.045). In contrast, in the p.R120W fibroblasts, no evidence of oxidative stress was observed (Fig. 4).","Whereas treatment with 10 µM resv eratrol produced no significant modification of CI activity (data not shown), treat ment with 25µM resveratrol modulated CI activity in CMT2K fibroblasts with a trend towards the restoration of CI activity in both p.C240Y and p.R120W fibroblasts. We also assessed t he effect of resveratrol in alleviating mitochondrial dysfunction in cells carrying GDAP1 m utations independently of the location and mutation type in the perspective of potential f uture therapeutic studies on CMT2K patients. Combining both patient families showed a significant improvement of CI activity after resveratrol treatment (Fig. 5, p<0.05).","The enzyme-activity reduction was significant for C240Y but not R120W in two-family fibroblast comparisons.","Permeabilized fibroblasts from both families had lower complex-I-substrate respiration and ATP synthesis under the experimental conditions.","MitoSOX, thiol and antioxidant readouts support oxidative stress in C240Y-family fibroblasts, whereas R120W-family cells did not show the same response.","The significant complex I effect comes from pooling the two families; allele-specific analyses were trends. 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It also cannot address the telomerase-independent component that the mouse work later identified, because the system retains endogenous telomerase throughout.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0000723","label":"telomere maintenance","display_label":"telomere maintenance","url":"http://purl.obolibrary.org/obo/GO_0000723"}],"pathways":[],"genes":[{"id":"hgnc:11824","label":"TINF2","display_label":"TINF2","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/11824"}],"chemicals":[],"readouts":[{"name":"Telomere length in cells expressing DC-mutant TIN2","description":null,"target":"Impaired Shelterin-Mediated Telomere Maintenance","direction":"DECREASED","interpretation":"Accelerated telomere shortening, reproducing the patient phenotype in a controlled human cell system.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:21536674","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/21536674","reference_title":"TIN2 protein dyskeratosis congenita missense mutants are defective in association with telomerase.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"ectopic expression of TIN2 with DC missense mutations in human cells led to accelerated telomere shortening, similar to the telomere phenotypes found in DC patients","explanation":"The telomere-length readout and the authors' own comparison of it to the patient phenotype."}],"notes":null},{"name":"Total cellular telomerase activity and telomere end protection status","description":null,"target":"Impaired Shelterin-Mediated Telomere Maintenance","direction":"UNCHANGED","interpretation":"A negative result that carries the argument: the shortening is not explained by less telomerase or by loss of end protection, which is what narrows the defect to recruitment.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:21536674","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/21536674","reference_title":"TIN2 protein dyskeratosis congenita missense mutants are defective in association with telomerase.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"However, this telomere shortening was not accompanied by changes in total telomerase activity, localization of TIN2, or telomere end protection status.","explanation":"The three measurements that were unchanged, and the reason the conclusion is specific."}],"notes":null}],"evidence":[{"reference":"PMID:21536674","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/21536674","reference_title":"TIN2 protein dyskeratosis congenita missense mutants are defective in association with telomerase.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"ectopic expression of TIN2 with DC missense mutations in human cells led to accelerated telomere shortening, similar to the telomere phenotypes found in DC patients","explanation":"The telomere-length readout and the authors' own comparison of it to the patient phenotype."},{"reference":"PMID:21536674","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/21536674","reference_title":"TIN2 protein dyskeratosis congenita missense mutants are defective in association with telomerase.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"However, this telomere shortening was not accompanied by changes in total telomerase activity, localization of TIN2, or telomere end protection status.","explanation":"The three measurements that were unchanged, and the reason the conclusion is specific."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Revesz_Syndrome","model_node_id":"model:kb/disorders/Revesz_Syndrome.yaml:Ectopic DC-cluster TIN2 missense expression in human cells","focus_node_id":"node:disorder%3ARevesz_Syndrome:pathophysiology:Impaired%20Shelterin-Mediated%20Telomere%20Maintenance","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Revesz_Syndrome.html#pathograph","nodes":[{"id":"model:kb/disorders/Revesz_Syndrome.yaml:Ectopic DC-cluster TIN2 missense expression in human cells","kind":"experimental_model","kind_label":"NAM model","label":"Ectopic DC-cluster TIN2 missense expression in human cells","description":"Human cells expressing TIN2 carrying dyskeratosis congenita cluster missense mutations. The system reproduces accelerated telomere shortening and was used to establish what the mutants can and cannot do: they lose telomerase association while leaving total telomerase activity, TIN2 localisation and telomere end protection intact.","url":"https://dismech.monarchinitiative.org/pages/disorders/Revesz_Syndrome.html#experimental-model-ectopic-dc-cluster-tin2-missense-expression-in-human-cells","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ARevesz_Syndrome:pathophysiology:Impaired%20Shelterin-Mediated%20Telomere%20Maintenance","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Shelterin-Mediated Telomere Maintenance","description":"Shelterin is the six-protein complex that coats the telomere and suppresses the DNA damage response there. TIN2 is its structural hub, binding TRF1 and TRF2 on the duplex telomeric DNA and TPP1 - and through TPP1, POT1 - on the single-stranded overhang. A DC-cluster variant leaves the complex assembled but impairs its regulation of telomere length.\nWhat exactly is impaired is genuinely disputed, and the two published accounts are set out as separate hypothesis groups rather than blended. One holds that DC-cluster TIN2 mutants lose the ability to recruit telomerase; the other, from a knock-in mouse, holds that they cause a telomerase-independent replication defect at the telomere. The experiments behind each are sound, they are not mutually exclusive, and no work has apportioned them.","url":"https://dismech.monarchinitiative.org/pages/disorders/Revesz_Syndrome.html#pathophysiology-impaired-shelterin-mediated-telomere-maintenance","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ARevesz_Syndrome:pathophysiology:Extreme%20Telomere%20Shortening","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Extreme Telomere Shortening","description":"Telomeres far below the first age-adjusted percentile - shorter, as a group, than in any other genetic subtype of dyskeratosis congenita. In the assembled Revesz cohort every patient with a measurement had a very short result, and in a large TINF2 series the telomere lengths were the shortest of all dyskeratosis congenita subtypes while telomerase RNA levels were normal, which localises the defect to the telomere rather than to the enzyme.\nThis is the quantitative link between the genotype and the severity, and the reason telomere length by flow-FISH is the functional screening test for the disease. Below some threshold, replication-limited tissues stop being replenished; which tissues fail first is what the branches below describe.","url":"https://dismech.monarchinitiative.org/pages/disorders/Revesz_Syndrome.html#pathophysiology-extreme-telomere-shortening","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ARevesz_Syndrome:pathophysiology:TINF2%20Exon%206%20Cluster%20Variant","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"TINF2 Exon 6 Cluster Variant","description":"A heterozygous germline TINF2 variant in a strikingly narrow window: every variant in genotyped Revesz patients has fallen in exon 6, between amino acids 280 and 289 of TIN2. The recurrent allele is c.845G>A, and the same residue - 282 - accounts for the majority of TINF2 dyskeratosis congenita variants generally. Frameshift alleles producing truncated TIN2 occur in the same window.\nThat window is the \"dyskeratosis congenita cluster\" of TIN2, and its constancy is the single most distinctive genetic fact about this disease. It is also the fact that most undermines Revesz as a separate entity: the identical variants are found in patients with classical dyskeratosis congenita who never develop the retinopathy. The founding TINF2 paper makes the point in its own data, reporting R282H across three unrelated probands of whom only one had Revesz syndrome. Genotype therefore cannot define this disease, and no modifier that does has been identified.","url":"https://dismech.monarchinitiative.org/pages/disorders/Revesz_Syndrome.html#pathophysiology-tinf2-exon-6-cluster-variant","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Revesz_Syndrome.yaml:Ectopic DC-cluster TIN2 missense expression in human cells","source_id":"model:kb/disorders/Revesz_Syndrome.yaml:Ectopic DC-cluster TIN2 missense expression in human cells","target_id":"node:disorder%3ARevesz_Syndrome:pathophysiology:Impaired%20Shelterin-Mediated%20Telomere%20Maintenance","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"Reproduces the molecular phenotype of a DC-cluster TIN2 allele - progressive telomere shortening - in human cells, and localises the defect to telomerase recruitment rather than to end protection.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ARevesz_Syndrome:1:0","source_id":"node:disorder%3ARevesz_Syndrome:pathophysiology:Impaired%20Shelterin-Mediated%20Telomere%20Maintenance","target_id":"node:disorder%3ARevesz_Syndrome:pathophysiology:Extreme%20Telomere%20Shortening","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Under the recruitment model, the DC-cluster variant reduces TPP1-dependent delivery of telomerase to the telomere, so telomeres are not replenished and shorten with every division.","intermediate_mechanisms":[],"hypothesis_groups":["tin2_telomerase_recruitment_defect"],"evidence_count":0},{"id":"causal:disorder%3ARevesz_Syndrome:1:1","source_id":"node:disorder%3ARevesz_Syndrome:pathophysiology:Impaired%20Shelterin-Mediated%20Telomere%20Maintenance","target_id":"node:disorder%3ARevesz_Syndrome:pathophysiology:Extreme%20Telomere%20Shortening","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[1]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Under the replication model, the DC-cluster variant makes the telomere a fragile replication substrate, producing attrition that persists in the complete absence of telomerase.","intermediate_mechanisms":[],"hypothesis_groups":["tin2_telomere_replication_defect"],"evidence_count":0},{"id":"causal:disorder%3ARevesz_Syndrome:0:0","source_id":"node:disorder%3ARevesz_Syndrome:pathophysiology:TINF2%20Exon%206%20Cluster%20Variant","target_id":"node:disorder%3ARevesz_Syndrome:pathophysiology:Impaired%20Shelterin-Mediated%20Telomere%20Maintenance","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"TIN2 is a structural hub of shelterin; a variant in its DC cluster impairs the complex's maintenance of telomere length. The step is direct, but which molecular activity is lost is disputed, so both hypothesis groups attach to the edge below it rather than here.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0}]}}],"mechanism_names":["Impaired Shelterin-Mediated Telomere Maintenance"],"relationships":["Recapitulates"],"fidelities":["Moderate"],"biological_scales":["Molecular"],"system_context_sources":["Linked mechanism biological scale"],"modeled_system_labels":["Molecular"],"biological_process_terms":[{"id":"GO:0000723","label":"telomere maintenance","display_label":"telomere maintenance","url":"http://purl.obolibrary.org/obo/GO_0000723"}],"biological_processes":["telomere maintenance"],"pathway_terms":[],"pathways":[],"gene_terms":[{"id":"hgnc:11824","label":"TINF2","display_label":"TINF2","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/11824"}],"genes":["TINF2"],"chemical_terms":[],"chemicals":[],"readout_names":["Telomere length in cells expressing DC-mutant TIN2","Total cellular telomerase activity and telomere end protection status"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:21536674","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/21536674","reference_title":"TIN2 protein dyskeratosis congenita missense mutants are defective in association with telomerase.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"ectopic expression of TIN2 with DC missense mutations in human cells led to accelerated telomere shortening, similar to the telomere phenotypes found in DC patients","explanation":"The telomere-length readout and the authors' own comparison of it to the patient phenotype."},{"reference":"PMID:21536674","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/21536674","reference_title":"TIN2 protein dyskeratosis congenita missense mutants are defective in association with telomerase.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"However, this telomere shortening was not accompanied by changes in total telomerase activity, localization of TIN2, or telomere end protection status.","explanation":"The three measurements that were unchanged, and the reason the conclusion is specific."}],"evidence_text":["ectopic expression of TIN2 with DC missense mutations in human cells led to accelerated telomere shortening, similar to the telomere phenotypes found in DC patients","However, this telomere shortening was not accompanied by changes in total telomerase activity, localization of TIN2, or telomere end protection status.","The telomere-length readout and the authors' own comparison of it to the patient phenotype.","The three measurements that were unchanged, and the reason the conclusion is specific."],"evidence_status":"Evidence recorded","metadata_completeness":60,"metadata_present":["Model category","NAMO class","Organism","Modeled mechanism","Publication","Evidence"],"metadata_missing":["Anatomy","Cell type","Cell source","Culture system"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Revesz_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Revesz_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Revesz_Syndrome.html#experimental-model-ectopic-dc-cluster-tin2-missense-expression-in-human-cells","source_anchor":"experimental-model-ectopic-dc-cluster-tin2-missense-expression-in-human-cells"},{"id":"model:kb/disorders/EDEM3-Congenital_Disorder_of_Glycosylation.yaml:EDEM3-CDG patient fibroblasts with EDEM3 complementation","name":"EDEM3-CDG patient fibroblasts with EDEM3 complementation","description":"Skin fibroblasts from affected individuals in families 1 and 3, studied by [2-3H]mannose pulse-chase N-glycan analysis before and after re-expression of wild-type EDEM3.","notes":null,"context_id":"disorder:EDEM3-Congenital_Disorder_of_Glycosylation","context_kind":"Disorder","disease_name":"EDEM3-Congenital Disorder of Glycosylation","disease_synonyms":["EDEM3-CDG","CDG2V","CDG-IIv","congenital disorder of glycosylation type IIv"],"disease_term":{"id":"MONDO:0030423","label":"congenital disorder of glycosylation, type 2v","display_label":"congenital disorder of glycosylation, type 2v","url":"http://purl.obolibrary.org/obo/MONDO_0030423"},"experimental_model_type":"PRIMARY_CELL_CULTURE","experimental_model_type_label":"Primary-cell culture","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},"organism_label":"Homo sapiens","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":null,"source_category":"Primary / biopsy-derived","culture_system":null,"publication":"PMID:34143952","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34143952","mechanisms":[{"target":"Deficient ER Mannose Trimming","target_url":"https://dismech.monarchinitiative.org/pages/disorders/EDEM3-Congenital_Disorder_of_Glycosylation.html#pathophysiology-deficient-er-mannose-trimming","relationship":"RECAPITULATES","relationship_label":"Recapitulates","fidelity":"HIGH","fidelity_label":"High","description":"Patient fibroblasts fail to trim M8B and M5 during the chase.","limitations":"Fibroblasts are not neural cells, so the model says nothing about the neurodevelopmental phenotype.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:1904382","label":"mannose trimming involved in glycoprotein ERAD pathway","display_label":"mannose trimming involved in glycoprotein ERAD pathway","url":"http://purl.obolibrary.org/obo/GO_1904382"}],"pathways":[],"genes":[{"id":"hgnc:16787","label":"EDEM3","display_label":"EDEM3","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/16787"}],"chemicals":[],"readouts":[],"evidence":[{"reference":"PMID:34143952","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/34143952","reference_title":"Bi-allelic variants in the ER quality-control mannosidase gene EDEM3 cause a congenital disorder of glycosylation.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"After 2 h of chase, the peaks for M7 and M4 did not appear in the cells of affected individuals (Figure 3B), indicating that the 1,2-alpha mannose residues were not removed from the M8B and M5 N-glycans during the chase, which is consistent with the absence of the biological function of EDEM3 (Figure 3A).","explanation":"The trimming defect measured directly in patient cells."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:EDEM3-Congenital_Disorder_of_Glycosylation","model_node_id":"model:kb/disorders/EDEM3-Congenital_Disorder_of_Glycosylation.yaml:EDEM3-CDG patient fibroblasts with EDEM3 complementation","focus_node_id":"node:disorder%3AEDEM3-Congenital_Disorder_of_Glycosylation:pathophysiology:Deficient%20ER%20Mannose%20Trimming","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/EDEM3-Congenital_Disorder_of_Glycosylation.html#pathograph","nodes":[{"id":"model:kb/disorders/EDEM3-Congenital_Disorder_of_Glycosylation.yaml:EDEM3-CDG patient fibroblasts with EDEM3 complementation","kind":"experimental_model","kind_label":"NAM model","label":"EDEM3-CDG patient fibroblasts with EDEM3 complementation","description":"Skin fibroblasts from affected individuals in families 1 and 3, studied by [2-3H]mannose pulse-chase N-glycan analysis before and after re-expression of wild-type EDEM3.","url":"https://dismech.monarchinitiative.org/pages/disorders/EDEM3-Congenital_Disorder_of_Glycosylation.html#experimental-model-edem3-cdg-patient-fibroblasts-with-edem3-complementation","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEDEM3-Congenital_Disorder_of_Glycosylation:pathophysiology:Deficient%20ER%20Mannose%20Trimming","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Deficient ER Mannose Trimming","description":"Without EDEM3, alpha-1,2-linked mannose is not trimmed from Man8GlcNAc2 isomer B to Man7-5GlcNAc2, and Man5GlcNAc2 is not trimmed to Man4GlcNAc2, with accumulation of Glc1Man5GlcNAc2 in patient fibroblasts. The authors suggest that this Man5 species may come from the lipid-linked oligosaccharide precursor rather than from trimming, which would imply an additional effect on precursor synthesis; this is speculative. In purified enzyme assays EDEM3 alone converts M8B to M7, M6 and M5 and is a major alpha-1,2-mannosidase for this second trimming step.","url":"https://dismech.monarchinitiative.org/pages/disorders/EDEM3-Congenital_Disorder_of_Glycosylation.html#pathophysiology-deficient-er-mannose-trimming","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEDEM3-Congenital_Disorder_of_Glycosylation:pathophysiology:Altered%20Plasma%20and%20Cellular%20High-Mannose%20N-Glycan%20Profile","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Altered Plasma and Cellular High-Mannose N-Glycan Profile","description":"Secreted and cellular glycoproteins carry fewer trimmed high-mannose glycans. Patient plasma shows reduced Man3-Man7 species with normal or mildly raised Man8 and Man9, giving reduced Man5:Man9, Man6:Man9, Man7:Man9 and Man3:Man4 ratios and a raised Man9:Man3 ratio. Transferrin glycosylation, the standard CDG screen, is normal.","url":"https://dismech.monarchinitiative.org/pages/disorders/EDEM3-Congenital_Disorder_of_Glycosylation.html#pathophysiology-altered-plasma-and-cellular-high-mannose-n-glycan-profile","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEDEM3-Congenital_Disorder_of_Glycosylation:pathophysiology:Biallelic%20EDEM3%20Loss-of-Function%20Variants","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Biallelic EDEM3 Loss-of-Function Variants","description":"Mostly protein-truncating EDEM3 variants (frameshift, nonsense and splice donor) that trigger nonsense-mediated mRNA decay, leaving about 17-18% of normal transcript and no detectable EDEM3 protein in patient cells. One family carries two missense variants in the GH47 mannosidase domain. EDEM1, which performs an overlapping trimming step, is not upregulated.","url":"https://dismech.monarchinitiative.org/pages/disorders/EDEM3-Congenital_Disorder_of_Glycosylation.html#pathophysiology-biallelic-edem3-loss-of-function-variants","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEDEM3-Congenital_Disorder_of_Glycosylation:pathophysiology:Blunted%20PERK-Mediated%20Unfolded%20Protein%20Response","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Blunted PERK-Mediated Unfolded Protein Response","description":"Lymphoblastoid cells from affected individuals induce PERK (EIF2AK3) mRNA less than control cells after tunicamycin (measured by quantitative PCR only); ATF6 and IRE1 changes were not significant (three patient and three control lines). In contrast, EDEM3 knockout in hepatoma cells activates ER stress and apoptosis, so the direction of the stress response appears to depend on the cell type.","url":"https://dismech.monarchinitiative.org/pages/disorders/EDEM3-Congenital_Disorder_of_Glycosylation.html#pathophysiology-blunted-perk-mediated-unfolded-protein-response","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEDEM3-Congenital_Disorder_of_Glycosylation:pathophysiology:Impaired%20Glycoprotein%20ER-Associated%20Degradation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Glycoprotein ER-Associated Degradation","description":"Trimmed high-mannose glycans are the signal recognised by the lectins that deliver misfolded glycoproteins to ERAD. EDEM3 overexpression accelerates ERAD of misfolded glycoproteins, and combined EDEM1 and EDEM3 loss delays it. Slower clearance of misfolded glycoproteins is therefore the expected consequence of EDEM3 loss, but it has not been measured in patient cells.","url":"https://dismech.monarchinitiative.org/pages/disorders/EDEM3-Congenital_Disorder_of_Glycosylation.html#pathophysiology-impaired-glycoprotein-er-associated-degradation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEDEM3-Congenital_Disorder_of_Glycosylation:phenotype:Neurodevelopmental%20Delay","kind":"phenotype","kind_label":"Phenotype","label":"Neurodevelopmental Delay","description":"Developmental delay and/or intellectual disability in all reported individuals, described as neurodevelopmental delay. Brain MRI in three families showed no structural abnormality or myelination defect.","url":"https://dismech.monarchinitiative.org/pages/disorders/EDEM3-Congenital_Disorder_of_Glycosylation.html#phenotype-neurodevelopmental-delay","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/EDEM3-Congenital_Disorder_of_Glycosylation.yaml:EDEM3-CDG patient fibroblasts with EDEM3 complementation","source_id":"model:kb/disorders/EDEM3-Congenital_Disorder_of_Glycosylation.yaml:EDEM3-CDG patient fibroblasts with EDEM3 complementation","target_id":"node:disorder%3AEDEM3-Congenital_Disorder_of_Glycosylation:pathophysiology:Deficient%20ER%20Mannose%20Trimming","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"HIGH","causal_link_type":null,"causal_link_type_label":null,"description":"Patient fibroblasts fail to trim M8B and M5 during the chase.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AEDEM3-Congenital_Disorder_of_Glycosylation:0:0","source_id":"node:disorder%3AEDEM3-Congenital_Disorder_of_Glycosylation:pathophysiology:Biallelic%20EDEM3%20Loss-of-Function%20Variants","target_id":"node:disorder%3AEDEM3-Congenital_Disorder_of_Glycosylation:pathophysiology:Deficient%20ER%20Mannose%20Trimming","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AEDEM3-Congenital_Disorder_of_Glycosylation:1:0","source_id":"node:disorder%3AEDEM3-Congenital_Disorder_of_Glycosylation:pathophysiology:Deficient%20ER%20Mannose%20Trimming","target_id":"node:disorder%3AEDEM3-Congenital_Disorder_of_Glycosylation:pathophysiology:Altered%20Plasma%20and%20Cellular%20High-Mannose%20N-Glycan%20Profile","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AEDEM3-Congenital_Disorder_of_Glycosylation:1:3","source_id":"node:disorder%3AEDEM3-Congenital_Disorder_of_Glycosylation:pathophysiology:Deficient%20ER%20Mannose%20Trimming","target_id":"node:disorder%3AEDEM3-Congenital_Disorder_of_Glycosylation:pathophysiology:Blunted%20PERK-Mediated%20Unfolded%20Protein%20Response","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[3]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"Proposed link. The authors connect the Glc1Man5GlcNAc2 accumulation seen in patient fibroblasts to an impaired unfolded protein response, and offer two readings of the blunted PERK induction: an impaired response, or an increased capacity to eliminate misfolded proteins. 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Mannose trimming generates the glycan signal that targets misfolded glycoproteins for ERAD, and loss of EDEM1 and EDEM3 together delays ERAD in cultured cells, but degradation of ERAD substrates has not been measured in EDEM3-CDG patient cells.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AEDEM3-Congenital_Disorder_of_Glycosylation:1:2","source_id":"node:disorder%3AEDEM3-Congenital_Disorder_of_Glycosylation:pathophysiology:Deficient%20ER%20Mannose%20Trimming","target_id":"node:disorder%3AEDEM3-Congenital_Disorder_of_Glycosylation:phenotype:Neurodevelopmental%20Delay","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[2]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"The link from the glycan defect to the neurodevelopmental phenotype rests on genetic association only. The intervening cellular steps are unknown, no neural model of EDEM3 deficiency exists, and the authors state that the mechanism remains to be determined.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":2}]}}],"mechanism_names":["Deficient ER Mannose Trimming"],"relationships":["Recapitulates"],"fidelities":["High"],"biological_scales":["Molecular"],"system_context_sources":["Linked mechanism biological scale"],"modeled_system_labels":["Molecular"],"biological_process_terms":[{"id":"GO:1904382","label":"mannose trimming involved in glycoprotein ERAD pathway","display_label":"mannose trimming involved in glycoprotein ERAD pathway","url":"http://purl.obolibrary.org/obo/GO_1904382"}],"biological_processes":["mannose trimming involved in glycoprotein ERAD 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absence of the biological function of EDEM3 (Figure 3A).","explanation":"The trimming defect measured directly in patient cells."}],"evidence_text":["After 2 h of chase, the peaks for M7 and M4 did not appear in the cells of affected individuals (Figure 3B), indicating that the 1,2-alpha mannose residues were not removed from the M8B and M5 N-glycans during the chase, which is consistent with the absence of the biological function of EDEM3 (Figure 3A).","The trimming defect measured directly in patient cells."],"evidence_status":"Evidence recorded","metadata_completeness":50,"metadata_present":["Model category","Organism","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Anatomy","Cell type","Cell source","Culture system"],"dataset_context":"None recorded in same 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of CDKN2A Cooperates with WWTR1(TAZ)-CAMTA1 Gene Fusion to Promote Tumor Progression in Epithelioid Hemangioendothelioma.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"These cell lines are \"addicted\" to the TC oncoprotein, replicate the EHE transcriptional profile, and generate EHE tumors when injected into immunodeficient mice.","explanation":"Documents oncogene addiction in the first EHE cell lines, the cellular basis for fusion-directed therapy."},{"reference":"PMID:39283723","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39283723","reference_title":"GDF-15 Predicts Epithelioid Hemangioendothelioma Aggressiveness and Is Downregulated by Sirolimus through ATF4/ATF5 Suppression.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"A patient-derived xenograft model and corresponding cell line were established from a patient with advanced EHE, demonstrating consistency with the original tumor in terms of histomorphology, WWTR1::CAMTA1 fusion presence, and 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The disease-relevant claim, that the equivalent program in developing human neurons is what fails in NEDHSS, is an extension from stem-cell and invertebrate systems and is therefore provisional.","url":"https://dismech.monarchinitiative.org/pages/disorders/Neurodevelopmental_Disorder_with_Hypotonia_and_Speech_Delay,_With_or_Without_Seizures.html#pathophysiology-deregulated-neurodevelopmental-mrna-translation-program","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ANeurodevelopmental_Disorder_with_Hypotonia_and_Speech_Delay:pathophysiology:Deregulated%20Cap-Dependent%20Translation%20Initiation%20and%2043S%20Scanning","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Deregulated Cap-Dependent Translation Initiation and 43S Scanning","description":"Within the eIF4F cap-binding complex, eIF4A resolves secondary structure in the 5' leader so that the 43S preinitiation complex can be loaded and can scan to the start codon; pharmacological clamping of eIF4A1/eIF4A2 onto RNA blocks exactly these steps. eIF4A2 recognises the 5' cap structure, permits mRNA loading onto the ribosome, and binds preferentially in the translation initiation region spanning the 5' UTR and the adjacent start of the coding sequence. 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Leukocyte cDNA assays found no aberrant splicing in the tested exon intervals.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Recessive_Nonsyndromic_Hearing_Loss_88.html#pathophysiology-elmod3-biallelic-loss-of-function","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"}],"edges":[{"id":"model-link:0:model:kb/disorders/Autosomal_Recessive_Nonsyndromic_Hearing_Loss_88.yaml:Elmod3-disrupted mouse embryonic fibroblasts","source_id":"model:kb/disorders/Autosomal_Recessive_Nonsyndromic_Hearing_Loss_88.yaml:Elmod3-disrupted mouse embryonic fibroblasts","target_id":"node:disorder%3AAutosomal_Recessive_Nonsyndromic_Hearing_Loss_88:pathophysiology:Reduced%20Primary%20Cilium%20Formation","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Measures","directed":false,"relationship":"MEASURES","fidelity":"LOW","causal_link_type":null,"causal_link_type_label":null,"description":"CRISPR disruption of Elmod3 in immortalized mouse embryonic fibroblasts reduces the fraction of ciliated cells after serum starvation. 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Engineered heterozygous ACTB Thr120Ile organoids reproduce this finding. Cleavage angle constrains possible division modes but does not by itself determine daughter-cell fate.","url":"https://dismech.monarchinitiative.org/pages/disorders/Baraitser-Winter_Cerebrofrontofacial_Syndrome.html#pathophysiology-actin-dependent-apical-progenitor-cleavage-plane-defect","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ABaraitser-Winter_Cerebrofrontofacial_Syndrome:phenotype:Microcephaly","kind":"phenotype","kind_label":"Phenotype","label":"Microcephaly","description":"Microcephaly may be prenatal or develop postnatally. 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Two such clones, referred to as CRTDi011-A–mutACTB-1 and CRTDi011-A–mutACTB-2, were used for the generation of cerebral organoids","explanation":"The engineered ACTB comparison uses two heterozygous clones in a control background; there is no analogous engineered ACTG1 comparison in this study."},{"reference":"PMID:41372632","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41372632","reference_title":"Cerebral organoids expressing mutant actin genes reveal cellular mechanism underlying microcephaly.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"anaphase AP cleavage plane angles ... revealed essentially the same phenotypes—with exception of the number of ventricle-like structures ... in the 30 days-old cr. ACTB Thr120Ile organoids as observed in the BWCFF-S ACTB Thr120Ile patient-derived organoids","explanation":"The results compare engineered and patient-derived ACTB Thr120Ile organoids. The ventricle-number phenotype did not reproduce, and the comparison is not an ACTG1 isogenic experiment."}],"evidence_text":["heterozygous single-cell clones were identified by Sanger Sequencing of the target region ... Two such clones, referred to as CRTDi011-A–mutACTB-1 and CRTDi011-A–mutACTB-2, were used for the generation of cerebral organoids","anaphase AP cleavage plane angles ... revealed essentially the same phenotypes—with exception of the number of ventricle-like structures ... in the 30 days-old cr. ACTB Thr120Ile organoids as observed in the BWCFF-S ACTB Thr120Ile patient-derived organoids","The engineered ACTB comparison uses two heterozygous clones in a control background; there is no analogous engineered ACTG1 comparison in this study.","The results compare engineered and patient-derived ACTB Thr120Ile organoids. The ventricle-number phenotype did not reproduce, and the comparison is not an ACTG1 isogenic experiment."],"evidence_status":"Evidence recorded","metadata_completeness":80,"metadata_present":["Model category","NAMO class","Organism","Cell type","Cell source","Modeled mechanism","Publication","Evidence"],"metadata_missing":["Anatomy","Culture system"],"dataset_context":"Available in same entry","context_dataset_ids":["dataset:https://data.ghga.de/dataset/ghgad98802067102801","dataset:https://www.ebi.ac.uk/biostudies/sourcedata/studies/s-scdt-10_1038-s44319-025-00647-7"],"candidate_dataset_ids":["dataset:https://data.ghga.de/dataset/ghgad98802067102801","dataset:https://www.ebi.ac.uk/biostudies/sourcedata/studies/s-scdt-10_1038-s44319-025-00647-7"],"source_path":"kb/disorders/Baraitser-Winter_Cerebrofrontofacial_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Baraitser-Winter_Cerebrofrontofacial_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Baraitser-Winter_Cerebrofrontofacial_Syndrome.html#experimental-model-engineered-actb-thr120ile-cerebral-organoids","source_anchor":"experimental-model-engineered-actb-thr120ile-cerebral-organoids"},{"id":"model:kb/disorders/CHD8-Related_Neurodevelopmental_Disorder_with_Overgrowth.yaml:Engineered CHD8 exon-1 iPSC cerebral organoids","name":"Engineered CHD8 exon-1 iPSC cerebral organoids","description":"Four engineered heterozygous frameshift clones and two control clones derive from one healthy donor. 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The model shows approximately halved protein and altered developmental transcription, including DLX6-AS1 and DLX1 upregulation.","url":"https://dismech.monarchinitiative.org/pages/disorders/CHD8-Related_Neurodevelopmental_Disorder_with_Overgrowth.html#experimental-model-engineered-chd8-exon-1-ipsc-cerebral-organoids","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACHD8-Related_Neurodevelopmental_Disorder_with_Overgrowth:pathophysiology:Dysregulation%20of%20Neurodevelopmental%20Gene%20Networks","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Dysregulation of Neurodevelopmental Gene Networks","description":"Human neural progenitor knockdown changes expression of chromatin regulators and a secondary network enriched for neurodevelopmental genes. Sugathan et al. reported 1,756 nominally significant genes, of which 369 passed false-discovery correction. Control-cell binding maps identified 7,324 sites, but most expression changes lacked a nearby CHD8-binding site. These results support direct and indirect regulation; pathway enrichment does not itself demonstrate reduced synapse assembly or axon guidance.","url":"https://dismech.monarchinitiative.org/pages/disorders/CHD8-Related_Neurodevelopmental_Disorder_with_Overgrowth.html#pathophysiology-dysregulation-of-neurodevelopmental-gene-networks","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ACHD8-Related_Neurodevelopmental_Disorder_with_Overgrowth:pathophysiology:Aberrant%20Long-Range%20Functional%20Connectivity","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Aberrant Long-Range Functional Connectivity","description":"Resting-state fMRI in the exon-3 Chd8 heterozygous mouse shows increased synchronized activity in specific cortico-hippocampal and auditory-parietal networks. The result is a model observation, not an established human diagnostic signature. Organoid lineage proportions and transcriptional enrichment do not directly establish its cause. A separate awake Olig1-Cre mouse imaging study found regional microstructural differences and exploratory connectivity changes; the connectivity comparisons did not survive multiple-testing correction, and that cohort did not reproduce increased social-contact time. Neither result establishes a universal direction of connectivity change.","url":"https://dismech.monarchinitiative.org/pages/disorders/CHD8-Related_Neurodevelopmental_Disorder_with_Overgrowth.html#pathophysiology-aberrant-long-range-functional-connectivity","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ACHD8-Related_Neurodevelopmental_Disorder_with_Overgrowth:pathophysiology:CHD8%20Haploinsufficiency","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"CHD8 Haploinsufficiency","description":"Heterozygous truncating, splice-disrupting and deletion alleles reduce functional CHD8 dosage. Approximately half-normal protein is measured in several engineered models, rather than in every patient. Haploinsufficiency is the principal mechanism; selected missense alleles can alter function without the same remodeling defect.","url":"https://dismech.monarchinitiative.org/pages/disorders/CHD8-Related_Neurodevelopmental_Disorder_with_Overgrowth.html#pathophysiology-chd8-haploinsufficiency","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACHD8-Related_Neurodevelopmental_Disorder_with_Overgrowth:pathophysiology:Delayed%20Cortical%20Spine%20Development","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Delayed Cortical Spine Development","description":"A 2025 preprint reports lower dendritic spine density and increased spine formation in adolescent constitutive Chd8 heterozygous mice. Adult spine density and dynamics are normal. This is a transient structural phenotype and does not establish persistent synapse loss in patients.","url":"https://dismech.monarchinitiative.org/pages/disorders/CHD8-Related_Neurodevelopmental_Disorder_with_Overgrowth.html#pathophysiology-delayed-cortical-spine-development","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ACHD8-Related_Neurodevelopmental_Disorder_with_Overgrowth:pathophysiology:Excitatory-Inhibitory%20Neuronal%20Trajectory%20Imbalance","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Excitatory-Inhibitory Neuronal Trajectory Imbalance","description":"Engineered female H9 embryonic-stem-cell cerebral organoids show earlier inhibitory-neuron production and delayed excitatory-neuron production around day 60, followed by excitatory expansion at day 120. These are transient lineage-proportion changes, not a measured functional excitation/inhibition ratio. The S62X allele, affecting only the long isoform, does not reproduce the enlargement of the other tested alleles.","url":"https://dismech.monarchinitiative.org/pages/disorders/CHD8-Related_Neurodevelopmental_Disorder_with_Overgrowth.html#pathophysiology-excitatory-inhibitory-neuronal-trajectory-imbalance","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ACHD8-Related_Neurodevelopmental_Disorder_with_Overgrowth:pathophysiology:Impaired%20Myelination","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Myelination","description":"Mouse Chd8 haploinsufficiency and Olig1-lineage heterozygous deletion impair myelination. This differs from increased glial markers or greater white-matter volume in primate models. Olig1-Cre also marks ventral interneuron progenitors, so behavioral changes cannot be assigned exclusively to mature oligodendrocytes.","url":"https://dismech.monarchinitiative.org/pages/disorders/CHD8-Related_Neurodevelopmental_Disorder_with_Overgrowth.html#pathophysiology-impaired-myelination","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ACHD8-Related_Neurodevelopmental_Disorder_with_Overgrowth:pathophysiology:Impaired%20Wnt%2Fbeta-Catenin%20Signal%20Transduction","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Wnt/beta-Catenin Signal Transduction","description":"In embryonic mouse cortical knockdown, CHD8 supports expression of Wnt transducers and Wnt reporter activity. Stabilized beta-catenin rescues progenitor and selected adult neuronal/behavioral abnormalities. This direction is context-specific: knockdown in HEK293T cells and adult striatal transcriptomes do not show the same response.","url":"https://dismech.monarchinitiative.org/pages/disorders/CHD8-Related_Neurodevelopmental_Disorder_with_Overgrowth.html#pathophysiology-impaired-wnt-beta-catenin-signal-transduction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ACHD8-Related_Neurodevelopmental_Disorder_with_Overgrowth:pathophysiology:Increased%20Gliogenesis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Increased Gliogenesis","description":"CHD8-disrupted cynomolgus monkey brains have increased astrocytic and oligodendroglial markers, and engineered newborn brain slices show enhanced glial proliferation. The embryo-edited series includes one aborted fetus, one stillborn animal and one surviving male. Different alleles, very small animal numbers and uncertain brain editing in the surviving animal limit inference about human disease.","url":"https://dismech.monarchinitiative.org/pages/disorders/CHD8-Related_Neurodevelopmental_Disorder_with_Overgrowth.html#pathophysiology-increased-gliogenesis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ACHD8-Related_Neurodevelopmental_Disorder_with_Overgrowth:pathophysiology:Increased%20Neural%20Progenitor%20Proliferation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Increased Neural Progenitor Proliferation","description":"Progenitor proliferation increases in engineered human cerebral organoids and zebrafish morphants. In the Hurley mouse allelic series, increased TBR2-positive basal progenitor proliferation occurs in mild hypomorphs with approximately 36% residual protein, but was not detected in approximately 50% heterozygotes. More severe depletion instead produces apoptosis and brain hypoplasia; the response is not monotonic.","url":"https://dismech.monarchinitiative.org/pages/disorders/CHD8-Related_Neurodevelopmental_Disorder_with_Overgrowth.html#pathophysiology-increased-neural-progenitor-proliferation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ACHD8-Related_Neurodevelopmental_Disorder_with_Overgrowth:pathophysiology:Reduced%20Aged-Cortex%20Proteostasis%20Response%20Signature","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced Aged-Cortex Proteostasis Response Signature","description":"Twelve-month-old male Chd8 p.Val986* heterozygous mice have reduced expression of unfolded-protein-response and chaperone pathways, accompanied by lower phospho-S6 staining. Whether these changes reflect impaired proteostasis, lower stress, or a blunted response remains unresolved. Most effects are small, selected individual genes are only nominal trends, and human progressive neurodegeneration is not established.","url":"https://dismech.monarchinitiative.org/pages/disorders/CHD8-Related_Neurodevelopmental_Disorder_with_Overgrowth.html#pathophysiology-reduced-aged-cortex-proteostasis-response-signature","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ACHD8-Related_Neurodevelopmental_Disorder_with_Overgrowth:pathophysiology:Reduced%20Neuronal%20Chromatin%20Accessibility","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced Neuronal Chromatin Accessibility","description":"Conditional CHD8 deletion in human stem-cell-derived excitatory neurons reduces accessibility at CHD8-bound promoters, especially ETS-motif-containing sites. The strong genome-wide result is from homozygous deletion; heterozygous changes are modest and not statistically significant at the highlighted sites. This supplies experimental support for a chromatin-accessibility mechanism without equating binding maps with remodeling failure in patients.","url":"https://dismech.monarchinitiative.org/pages/disorders/CHD8-Related_Neurodevelopmental_Disorder_with_Overgrowth.html#pathophysiology-reduced-neuronal-chromatin-accessibility","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ACHD8-Related_Neurodevelopmental_Disorder_with_Overgrowth:pathophysiology:REST-Mediated%20Repression%20of%20Neuronal%20Genes","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"REST-Mediated Repression of Neuronal Genes","description":"Reduced CHD8 is associated with enhanced REST-mediated repression in the Katayama mouse model, most prominently around E14.5. Neurodevelopmental gene-set timing is delayed in that model. REST activity has not been shown to explain every CHD8 allele or all human manifestations.","url":"https://dismech.monarchinitiative.org/pages/disorders/CHD8-Related_Neurodevelopmental_Disorder_with_Overgrowth.html#pathophysiology-rest-mediated-repression-of-neuronal-genes","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ACHD8-Related_Neurodevelopmental_Disorder_with_Overgrowth:pathophysiology:Shortened%20Neural%20Progenitor%20G1%20Phase","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Shortened Neural Progenitor G1 Phase","description":"In one H9 embryonic-stem-cell-derived neural progenitor clone with heterozygous CHD8 disruption, live-cell FUCCI imaging shows a shorter G1 phase without an overt S/G2/M change. 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EWS-FLI1 also upregulates glutamine uptake and one-carbon cycle genes, linking fusion-driven transcription to biosynthetic metabolism, redox state, and survival.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-atf4-serine-glycine-metabolic-reprogramming","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:BAF%20Complex%20Retargeting","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"BAF Complex Retargeting","description":"EWS-FLI1 uses the EWSR1 low-complexity/prion-like domain to retarget BRG1/BRM-associated factor (BAF/SWI-SNF) chromatin-remodeling complexes to tumor-specific enhancers. This neomorphic recruitment depends on tyrosine residues linked to phase-transition behavior of the EWSR1 domain and helps establish oncogenic enhancer activity.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-baf-complex-retargeting","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:DHX9%20Sequestration%20During%20Topoisomerase%20Stress","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"DHX9 Sequestration During Topoisomerase Stress","description":"Following topoisomerase I poison exposure, EWS-FLI1 sequesters DHX9 helicase and prevents resolution of drug-induced R-loops. Excess DHX9 or reduced fusion expression confers SN-38 resistance independent of measured proliferation and global transcription rates. This supports a protein-interaction contribution under topoisomerase stress, without proving complete independence from transcription or untreated tumor initiation.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-dhx9-sequestration-during-topoisomerase-stress","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:EWS-FLI1%20Chromatin%20Hub%20Dynamics","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"EWS-FLI1 Chromatin Hub Dynamics","description":"EWS-FLI1 low-complexity-domain interactions support GGAA-associated transcription within a narrow interaction-strength optimum. 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TRIM8-mediated turnover prevents toxic fusion accumulation. Engineered graded depletion and restoration of endogenous EWS-FLI1 produce persistent transcriptional changes and increased metastatic behavior at intermediate depletion in preclinical models. This does not establish a clinical hazard of a particular inhibitor dose. Independently of those engineered perturbations, single-cell profiling of patient tumors associates an intermediate range of inferred fusion activity with proliferation and oxidative phosphorylation, and cells on either side of that range with a hypoxia program. That is a cross-sectional association in tumors, not a demonstration that fusion dose sets the program.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-ews-fli1-dosage-and-state-plasticity","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:EZH2-Associated%20Differentiation%20Repression","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"EZH2-Associated Differentiation Repression","description":"EWS-FLI1 induces EZH2, which contributes to repression of differentiation-associated genes and maintenance of an undifferentiated state. Genetic depletion impairs clonogenicity and tumorigenicity in preclinical systems. This dependency is distinct from the heterogeneous PRC2 changes following STAG2 loss and does not imply that every Ewing tumor will respond to an EZH2 inhibitor.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-ezh2-associated-differentiation-repression","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:GGAA%20Microsatellite%20Enhancer%20Reprogramming","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"GGAA Microsatellite Enhancer Reprogramming","description":"EWS-FLI1 binds GGAA microsatellite repeats and canonical ETS motifs, remodeling the enhancer landscape. At GGAA repeats, multimeric EWS-FLI1 opens chromatin and creates de novo enhancers that contact target promoters; at conserved ETS enhancers, EWS-FLI1 can displace wild-type ETS factors and repress tumor suppressor and lineage-regulatory programs.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-ggaa-microsatellite-enhancer-reprogramming","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:NuRD-LSD1%20Transcriptional%20Repression","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"NuRD-LSD1 Transcriptional Repression","description":"EWS-FLI1 recruits NuRD-associated HDAC and LSD1 activities to repress tumor-suppressive and lineage-regulatory genes. Repression contributes to transformation alongside enhancer activation. CHD4 also maintains global chromatin architecture and survival, but this distinct dependency should not be equated with regulation of EWS-FLI1 transcriptional output.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-nurd-lsd1-transcriptional-repression","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:PARP1-Supported%20Fusion%20Transcription","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"PARP1-Supported Fusion Transcription","description":"PARP1 interacts with EWS-FLI1 and EWS-ERG and supports fusion-mediated transcription; EWS-FLI1 also maintains PARP1 expression. 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Fusion knockdown and POLQ rescue support causality in tested models. Proposed synthetic lethality with other repair pathways requires independent replication and clinical evaluation; this is an emerging additional repair defect rather than a reason to erase the BRCA1 literature.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-proposed-polq-splicing-and-mmej-defect","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:SLFN11-Dependent%20Replication%20Fork%20Arrest","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"SLFN11-Dependent Replication Fork Arrest","description":"EWS-FLI1 directly increases SLFN11 expression. SLFN11 blocks stressed replication forks and promotes susceptibility to DNA-damaging agents. Expression-outcome correlations are not a validated standalone clinical selection test. Loss of SLFN11 can confer treatment resistance and is associated with metabolic adaptation in Ewing models.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-slfn11-dependent-replication-fork-arrest","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:Transcription-Coupled%20R-loop%20Accumulation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Transcription-Coupled R-loop Accumulation","description":"EWS-FLI1-driven transcription and impaired regulation of damage-induced transcription promote RNA:DNA hybrids and replication stress in Ewing cell models. The stress state creates DNA-damage vulnerabilities and dependence on buffering pathways. 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current landscape of preclinical modeling used in Ewing sarcoma research encompassing both in vitro (cell lines and tumor organoids) and in vivo (mouse and nonmammalian xenografts) model systems.","explanation":"Supports tumor organoids as part of the Ewing sarcoma preclinical modeling landscape."}],"evidence_text":["Through an international collaborative effort between the Children's Oncology Group Bone Tumor Committee and the Euro Ewing Consortium, we review the current landscape of preclinical modeling used in Ewing sarcoma research encompassing both in vitro (cell lines and tumor organoids) and in vivo (mouse and nonmammalian xenografts) model systems.","Supports tumor organoids as part of the Ewing sarcoma preclinical modeling landscape."],"evidence_status":"Evidence recorded","metadata_completeness":90,"metadata_present":["Model category","NAMO class","Organism","Cell type","Cell source","Culture system","Modeled 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In an RCM troponin-T model, elevated resting myocardial stiffness was measured directly; in the MYL3 RCM model, both active and passive tension of papillary muscle were augmented. The same pair of quantities has since been measured in human cells: engineered cardiac tissue built from the cardiomyocytes of an FLNC restrictive cardiomyopathy patient shows increased passive tension and impaired relaxation velocity against a CRISPR-corrected isogenic control. Increased resting stiffness is the cellular basis of the restrictive filling that defines the disease.","url":"https://dismech.monarchinitiative.org/pages/disorders/Restrictive_Cardiomyopathy.html#pathophysiology-increased-resting-myocardial-stiffness-and-impaired-relaxation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ARestrictive_Cardiomyopathy:pathophysiology:Cardiac%20Fibroblast%20Stiffening%20and%20Fibroblast-Cardiomyocyte%20Crosstalk","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Cardiac Fibroblast Stiffening and Fibroblast-Cardiomyocyte Crosstalk","description":"A second, non-myocyte contribution to the stiff ventricle, and the arm that matters for the sizeable fraction of patients in whom no sarcomere variant is found - a third of genotyped children in a national pediatric cohort, and more than half in the series behind the fibroblast work. Cardiac fibroblasts explanted from children with idiopathic RCM are themselves mechanically abnormal - measured by atomic force microscopy they are stiffer and more viscous, and less fluid, than control fibroblasts - with a transcriptional signature of altered cytoskeletal signalling (cytoskeletal actin-associated genes up, several tubulin genes down). Because fibroblasts restrain cardiomyocyte relaxation through humoral factors and direct cell-cell contact, a stiffened fibroblast population acts on diastolic function independently of the myofilament, which is why this node is curated as a parallel amplifier of myocardial stiffness rather than as a step downstream of the sarcomeric lesion.","url":"https://dismech.monarchinitiative.org/pages/disorders/Restrictive_Cardiomyopathy.html#pathophysiology-cardiac-fibroblast-stiffening-and-fibroblast-cardiomyocyte-crosstalk","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ARestrictive_Cardiomyopathy:pathophysiology:Restrictive%20Filling%20Physiology","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Restrictive Filling Physiology","description":"The stiff, fibrotic, poorly relaxing ventricle produces the hemodynamic signature of RCM: severely impaired diastolic filling with preserved systolic function and non-dilated ventricles, so that atrial pressures rise and the atria enlarge markedly to maintain filling. This restrictive filling pattern is the defining physiology that separates RCM from the dilated and hypertrophic patterns.","url":"https://dismech.monarchinitiative.org/pages/disorders/Restrictive_Cardiomyopathy.html#pathophysiology-restrictive-filling-physiology","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ARestrictive_Cardiomyopathy:pathophysiology:Sarcomeric%20or%20Cytoskeletal%20Variant%20with%20Increased%20Myofilament%20Tension","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Sarcomeric or Cytoskeletal Variant with Increased Myofilament Tension","description":"The initiating lesion in primary RCM is a variant in a sarcomeric thin-filament or myosin gene, or in a cytoskeletal/Z-disc protein (desmin, filamin C, myopalladin), that raises myofilament tension or destabilises the apparatus that anchors it. Two evidenced archetypes illustrate the myofilament route: a cardiac troponin-T variant that increases the number of actively cycling myosin cross-bridges, and a myosin essential light chain variant (MYL3 E143K) that produces myosin hypercontractility (increased duty ratio, actin-binding affinity, and actin-activated ATPase). The mutant protein is incorporated into the sarcomere and shifts the myocyte toward a hypercontractile, poorly relaxing state. The cytoskeletal route reaches the same node by a different lesion in kind - failure of intermediate-filament assembly for desmin, disturbed myofibrillogenesis for the restrictive myopalladin allele - which is why the node is named for the sarcomeric *or* cytoskeletal variant rather than for the sarcomere alone.","url":"https://dismech.monarchinitiative.org/pages/disorders/Restrictive_Cardiomyopathy.html#pathophysiology-sarcomeric-or-cytoskeletal-variant-with-increased-myofilament-tension","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Restrictive_Cardiomyopathy.yaml:FLNC RCM patient iPSC-derived cardiomyocytes and 3D engineered cardiac tissue","source_id":"model:kb/disorders/Restrictive_Cardiomyopathy.yaml:FLNC RCM patient iPSC-derived cardiomyocytes and 3D engineered cardiac tissue","target_id":"node:disorder%3ARestrictive_Cardiomyopathy:pathophysiology:Increased%20Resting%20Myocardial%20Stiffness%20and%20Impaired%20Relaxation","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"Mutant engineered tissues reproduce both halves of the node - raised passive tension and slowed relaxation - in human cells, against an isogenic control.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ARestrictive_Cardiomyopathy:2:0","source_id":"node:disorder%3ARestrictive_Cardiomyopathy:pathophysiology:Cardiac%20Fibroblast%20Stiffening%20and%20Fibroblast-Cardiomyocyte%20Crosstalk","target_id":"node:disorder%3ARestrictive_Cardiomyopathy:pathophysiology:Increased%20Resting%20Myocardial%20Stiffness%20and%20Impaired%20Relaxation","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[0]","label":"Indirectly causes (known intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_KNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Known Intermediates","description":"Mechanically abnormal fibroblasts contribute to the stiffness of the myocardium as a tissue and restrain cardiomyocyte relaxation.","intermediate_mechanisms":["Fibroblast-derived humoral factors restraining cardiomyocyte relaxation","Direct fibroblast-cardiomyocyte contact"],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ARestrictive_Cardiomyopathy:1:0","source_id":"node:disorder%3ARestrictive_Cardiomyopathy:pathophysiology:Increased%20Resting%20Myocardial%20Stiffness%20and%20Impaired%20Relaxation","target_id":"node:disorder%3ARestrictive_Cardiomyopathy:pathophysiology:Restrictive%20Filling%20Physiology","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"A stiff, poorly relaxing ventricle cannot fill normally in diastole.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ARestrictive_Cardiomyopathy:0:0","source_id":"node:disorder%3ARestrictive_Cardiomyopathy:pathophysiology:Sarcomeric%20or%20Cytoskeletal%20Variant%20with%20Increased%20Myofilament%20Tension","target_id":"node:disorder%3ARestrictive_Cardiomyopathy:pathophysiology:Increased%20Resting%20Myocardial%20Stiffness%20and%20Impaired%20Relaxation","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Hypercontractility and increased passive tension raise resting myocardial stiffness and impair diastolic relaxation.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0}]}}],"mechanism_names":["Increased Resting Myocardial Stiffness and Impaired Relaxation"],"relationships":["Recapitulates"],"fidelities":["Moderate"],"biological_scales":["Cellular"],"system_context_sources":["Model-level cell type","Linked mechanism cell type","Linked mechanism biological scale"],"modeled_system_labels":["cardiac muscle cell","Cellular"],"biological_process_terms":[{"id":"GO:0055117","label":"regulation of cardiac muscle contraction","display_label":"Regulation of Cardiac Muscle Contraction","url":"http://purl.obolibrary.org/obo/GO_0055117"}],"biological_processes":["regulation of cardiac muscle contraction"],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":["Passive tension of engineered cardiac tissue","Cardiomyocyte relaxation and calcium kinetics in 2D culture"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:36921598","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/36921598","reference_title":"Engineered cardiac tissue model of restrictive cardiomyopathy for drug discovery.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Together, these data demonstrate an engineered cardiac tissue model of RCM and establish the translational potential of this precision medicine approach to identify therapeutics targeting myocardial relaxation.","explanation":"The authors' own statement of what the system is for, which is the claim this model entry makes: a human-cell platform for the relaxation defect."},{"reference":"PMID:36921598","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/36921598","reference_title":"Engineered cardiac tissue model of restrictive cardiomyopathy for drug discovery.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"mutant engineered cardiac tissues (ECTs) demonstrate increased passive tension and impaired relaxation velocity compared with isogenic controls","explanation":"Reports the passive-tension measurement behind this readout."},{"reference":"PMID:36921598","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/36921598","reference_title":"Engineered cardiac tissue model of restrictive cardiomyopathy for drug discovery.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) with this variant display impaired relaxation and reduced calcium kinetics in 2D culture when compared with a CRISPR-Cas9-corrected isogenic control line.","explanation":"Reports the monolayer relaxation and calcium measurements behind this readout."}],"evidence_text":["Together, these data demonstrate an engineered cardiac tissue model of RCM and establish the translational potential of this precision medicine approach to identify therapeutics targeting myocardial relaxation.","mutant engineered cardiac tissues (ECTs) demonstrate increased passive tension and impaired relaxation velocity compared with isogenic controls","Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) with this variant display impaired relaxation and reduced calcium kinetics in 2D culture when compared with a CRISPR-Cas9-corrected isogenic control line.","The authors' own statement of what the system is for, which is the claim this model entry makes: a human-cell platform for the relaxation defect.","Reports the passive-tension measurement behind this readout.","Reports the monolayer relaxation and calcium measurements behind this readout."],"evidence_status":"Evidence recorded","metadata_completeness":80,"metadata_present":["Model category","Organism","Cell type","Cell source","Culture system","Modeled 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biomechanical stimulation, enabling controlled testing of tumor-stroma signaling, IGF-1R/STAT3 biology, and drug-resistance mechanisms that are absent from standard monolayer systems.","notes":null,"context_id":"disorder:Ewing_Sarcoma","context_kind":"Disorder","disease_name":"Ewing Sarcoma","disease_synonyms":[],"disease_term":{"id":"MONDO:0012817","label":"Ewing sarcoma","display_label":"Ewing sarcoma","url":"http://purl.obolibrary.org/obo/MONDO_0012817"},"experimental_model_type":"CO_CULTURE","experimental_model_type_label":"Co-culture","namo_type":"namo:CoCulture","declared_namo_class_name":null,"namo_class_name":"CoCulture","namo_class_label":"Co Culture","namo_description":"Co-culture systems combining multiple cell types to mimic  microenvironments and cell-cell interactions.","namo_docs_url":"https://monarch-initiative.github.io/namo/elements/CoCulture/","namo_ontology_url":"https://w3id.org/monarch-initiative/namo/CoCulture","namo_mapping_basis":"Safe mapping from DisMech category","namo_class_in_schema":true,"namo_schema_status":"Defined in NAMO schema used for this build","modality":"Cellular system","organism":{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},"organism_label":"Homo sapiens","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[{"id":"CL:0000134","label":"mesenchymal stem cell","display_label":"mesenchymal stem cell","url":"http://purl.obolibrary.org/obo/CL_0000134"}],"model_cell_type_labels":["mesenchymal stem cell"],"linked_cell_types":[{"id":"CL:0000134","label":"mesenchymal stem cell","display_label":"mesenchymal stem cell","url":"http://purl.obolibrary.org/obo/CL_0000134"}],"linked_cell_type_labels":["mesenchymal stem cell"],"cell_types":[{"id":"CL:0000134","label":"mesenchymal stem cell","display_label":"mesenchymal stem cell","url":"http://purl.obolibrary.org/obo/CL_0000134"}],"cell_type_labels":["mesenchymal stem cell"],"conditions":["Ewing sarcoma","tumor-stroma coculture","flow perfusion"],"cell_source":"Ewing sarcoma cells cocultured with mesenchymal stem cells","source_category":"Stem / progenitor-derived","culture_system":"3D scaffold coculture in a flow perfusion bioreactor","publication":"PMID:27923328","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/27923328","mechanisms":[{"target":"Tumor-Stroma IL-6/STAT3 Signaling","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-tumor-stroma-il-6-stat3-signaling","relationship":"NOT_SPECIFIED","relationship_label":"Not Specified","fidelity":"NOT_SPECIFIED","fidelity_label":"Not Specified","description":"Assays IL-6/STAT3 tumor-stroma signaling and drug response under biophysical stimulation; it does not test developmental IGF-1/YAP1 initiation.","limitations":null,"biological_scale":null,"anatomy":[],"cell_types":[{"id":"CL:0000134","label":"mesenchymal stem cell","display_label":"mesenchymal stem cell","url":"http://purl.obolibrary.org/obo/CL_0000134"}],"biological_processes":[{"id":"GO:0070102","label":"interleukin-6-mediated signaling pathway","display_label":"interleukin-6-mediated signaling pathway","url":"http://purl.obolibrary.org/obo/GO_0070102"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[],"evidence":[],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Ewing_Sarcoma","model_node_id":"model:kb/disorders/Ewing_Sarcoma.yaml:Flow-perfusion Ewing sarcoma 3D scaffold coculture","focus_node_id":"node:disorder%3AEwing_Sarcoma:pathophysiology:Tumor-Stroma%20IL-6%2FSTAT3%20Signaling","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathograph","nodes":[{"id":"model:kb/disorders/Ewing_Sarcoma.yaml:Flow-perfusion Ewing sarcoma 3D scaffold coculture","kind":"experimental_model","kind_label":"NAM model","label":"Flow-perfusion Ewing sarcoma 3D scaffold coculture","description":"Flow-perfusion 3D scaffold cocultures combine Ewing sarcoma cells with mesenchymal stromal cells under biomechanical stimulation, enabling controlled testing of tumor-stroma signaling, IGF-1R/STAT3 biology, and drug-resistance mechanisms that are absent from standard monolayer 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This established-tumor microenvironment mechanism is distinct from IGF-1/YAP1 developmental initiation.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-tumor-stroma-il-6-stat3-signaling","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:Tumor%20Cell%20Proliferation%20and%20Survival","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Tumor Cell Proliferation and Survival","description":"Multiple fusion-driven mechanisms converge on tumor cell proliferation and survival: core regulatory circuitry sustains oncogenic signaling, metabolic reprogramming supplies biomass and redox buffering, and replication-stress adaptation prevents apoptosis during genotoxic stress.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-tumor-cell-proliferation-and-survival","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Ewing_Sarcoma.yaml:Flow-perfusion Ewing sarcoma 3D scaffold coculture","source_id":"model:kb/disorders/Ewing_Sarcoma.yaml:Flow-perfusion Ewing sarcoma 3D scaffold coculture","target_id":"node:disorder%3AEwing_Sarcoma:pathophysiology:Tumor-Stroma%20IL-6%2FSTAT3%20Signaling","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Not Specified","directed":false,"relationship":"NOT_SPECIFIED","fidelity":"NOT_SPECIFIED","causal_link_type":null,"causal_link_type_label":null,"description":"Assays IL-6/STAT3 tumor-stroma signaling and drug response under biophysical stimulation; it does not test developmental IGF-1/YAP1 initiation.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3AEwing_Sarcoma:24:0","source_id":"node:disorder%3AEwing_Sarcoma:pathophysiology:Tumor-Stroma%20IL-6%2FSTAT3%20Signaling","target_id":"node:disorder%3AEwing_Sarcoma:pathophysiology:Tumor%20Cell%20Proliferation%20and%20Survival","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[24].downstream[0]","label":"Indirectly causes (known intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_KNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Known Intermediates","description":"Stromal cytokine signaling modifies tumor-cell survival and drug response in a tissue-engineered model.","intermediate_mechanisms":["IL-6/STAT3 activation"],"hypothesis_groups":["canonical_fusion_enhanceropathy_model"],"evidence_count":1}]}},{"target":"Tumor Cell Proliferation and Survival","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-tumor-cell-proliferation-and-survival","relationship":"NOT_SPECIFIED","relationship_label":"Not Specified","fidelity":"NOT_SPECIFIED","fidelity_label":"Not Specified","description":"Models stromal support of growth and drug-resistance phenotypes.","limitations":null,"biological_scale":null,"anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0008283","label":"cell population proliferation","display_label":"cell population proliferation","url":"http://purl.obolibrary.org/obo/GO_0008283"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[],"evidence":[],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Ewing_Sarcoma","model_node_id":"model:kb/disorders/Ewing_Sarcoma.yaml:Flow-perfusion Ewing sarcoma 3D scaffold coculture","focus_node_id":"node:disorder%3AEwing_Sarcoma:pathophysiology:Tumor%20Cell%20Proliferation%20and%20Survival","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathograph","nodes":[{"id":"model:kb/disorders/Ewing_Sarcoma.yaml:Flow-perfusion Ewing sarcoma 3D scaffold coculture","kind":"experimental_model","kind_label":"NAM model","label":"Flow-perfusion Ewing sarcoma 3D scaffold coculture","description":"Flow-perfusion 3D scaffold cocultures combine Ewing sarcoma cells with mesenchymal stromal cells under biomechanical stimulation, enabling controlled testing of tumor-stroma signaling, IGF-1R/STAT3 biology, and drug-resistance mechanisms that are absent from standard monolayer systems.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#experimental-model-flow-perfusion-ewing-sarcoma-3d-scaffold-coculture","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:Tumor%20Cell%20Proliferation%20and%20Survival","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Tumor Cell Proliferation and Survival","description":"Multiple fusion-driven mechanisms converge on tumor cell proliferation and survival: core regulatory circuitry sustains oncogenic signaling, metabolic reprogramming supplies biomass and redox buffering, and replication-stress adaptation prevents apoptosis during genotoxic stress.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-tumor-cell-proliferation-and-survival","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:ATF4-Serine-Glycine%20Metabolic%20Reprogramming","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"ATF4-Serine-Glycine Metabolic Reprogramming","description":"EWS-FLI1 and menin converge on ATF4 to activate a serine synthesis pathway transcriptional program. EWS-FLI1 also upregulates glutamine uptake and one-carbon cycle genes, linking fusion-driven transcription to biosynthetic metabolism, redox state, and survival.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-atf4-serine-glycine-metabolic-reprogramming","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:CHD4%20Chromatin%20Architecture%20Maintenance","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"CHD4 Chromatin Architecture Maintenance","description":"CHD4/NuRD maintains global chromatin structure and limits spontaneous DNA damage in Ewing cells. Despite colocalization with EWS-FLI1 at enhancers, the reported survival effect did not operate by changing EWS-FLI1 activity or its oncogenic expression program. CHD4 loss causes apoptosis and increases sensitivity to DNA-damaging agents; combined CHD4 depletion and olaparib suppressed xenograft growth.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-chd4-chromatin-architecture-maintenance","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:Core%20Regulatory%20Circuitry%20Activation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Core Regulatory Circuitry Activation","description":"EWS-FLI1 activates super-enhancers controlling a core regulatory circuitry composed of transcription factors including KLF15, TCF4, and NKX2-2. These factors reinforce their own and each other's regulatory elements and cooperate with EWS-FLI1 to sustain proliferation, survival signaling, and the Ewing transcriptional state.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-core-regulatory-circuitry-activation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:ETV6%20GGAA%20Counter-Regulation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"ETV6 GGAA Counter-Regulation","description":"ETV6 is a native ETS-family factor that competes with EWS-FLI1 at select short GGAA-repeat elements. This counter-regulatory layer restrains part of the enhanceropathy, and forced ETV6 degradation can paradoxically increase EWS-FLI1 transcriptional stress and tumor cell death.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-etv6-ggaa-counter-regulation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:EWS-FLI1%20Dosage%20and%20State%20Plasticity","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"EWS-FLI1 Dosage and State Plasticity","description":"Fusion abundance and low-complexity-domain interaction strength are related but distinct control variables. TRIM8-mediated turnover prevents toxic fusion accumulation. Engineered graded depletion and restoration of endogenous EWS-FLI1 produce persistent transcriptional changes and increased metastatic behavior at intermediate depletion in preclinical models. This does not establish a clinical hazard of a particular inhibitor dose. Independently of those engineered perturbations, single-cell profiling of patient tumors associates an intermediate range of inferred fusion activity with proliferation and oxidative phosphorylation, and cells on either side of that range with a hypoxia program. That is a cross-sectional association in tumors, not a demonstration that fusion dose sets the program.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-ews-fli1-dosage-and-state-plasticity","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:GGAA%20Microsatellite%20Germline%20Susceptibility%20Architecture","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"GGAA Microsatellite Germline Susceptibility Architecture","description":"Germline variation in GGAA microsatellite architecture can determine how strongly the acquired EWS-FLI1 fusion converts a locus into a neo-enhancer. At EGR2 and RREB1 susceptibility loci, longer or newly contiguous GGAA repeat alleles increase EWS-FLI1 binding and enhancer output, linking inherited repeat length to the somatic enhanceropathy and proliferative transcriptional programs.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-ggaa-microsatellite-germline-susceptibility-architecture","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:IGF-1%2FYAP1%20Developmental%20Cooperation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"IGF-1/YAP1 Developmental Cooperation","description":"Transient IGF-1 exposure at concentrations chosen to mimic pubertal serum levels reprogrammed limb-derived mesenchymal cells from EWS-FLI1-mutant mice through a YAP1-centered mechanism and enabled stable tumorigenicity. This model suggests a developmental cooperating signal but does not establish puberty as the time of human initiation, a universal IGF-1 requirement, or a human cell of origin. YAP1/TAZ can oppose fusion transcription while promoting aggressive behavior in established tumors, so initiation and maintenance contexts require separate testing.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-igf-1-yap1-developmental-cooperation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:NuRD-LSD1%20Transcriptional%20Repression","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"NuRD-LSD1 Transcriptional Repression","description":"EWS-FLI1 recruits NuRD-associated HDAC and LSD1 activities to repress tumor-suppressive and lineage-regulatory genes. Repression contributes to transformation alongside enhancer activation. CHD4 also maintains global chromatin architecture and survival, but this distinct dependency should not be equated with regulation of EWS-FLI1 transcriptional output.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-nurd-lsd1-transcriptional-repression","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:Osseous%20Tumor%20Expansion%20and%20Bone%20Destruction","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Osseous Tumor Expansion and Bone Destruction","description":"In osseous Ewing sarcoma, infiltrative tumor growth destroys the affected bone and can extend through cortex into soft tissue. Local structural injury contributes to pain, swelling and fracture risk. These consequences are specific to osseous or bone-involving disease; treatment can also contribute to later fractures.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-osseous-tumor-expansion-and-bone-destruction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:SLFN11-Loss-Associated%20Lipid%20Remodeling","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"SLFN11-Loss-Associated Lipid Remodeling","description":"SLFN11-deficient Ewing models show reduced GPD2 expression and increased glycerophospholipid biosynthesis. Pharmacologic inhibition of glycerophospholipid synthesis increased SN-38 sensitivity in vitro, with modest and cell-line-dependent combination effects. The regulatory link from SLFN11 loss to GPD2 suppression and human predictive value remain unresolved. This loss state is not represented as a positive consequence of SLFN11 fork arrest.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-slfn11-loss-associated-lipid-remodeling","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3AEwing_Sarcoma:phenotype:Soft%20Tissue%20Mass%20%2F%20Localized%20Swelling","kind":"phenotype","kind_label":"Phenotype","label":"Soft Tissue Mass / Localized Swelling","description":"A palpable mass or localized swelling may develop as tumor extends through the bone cortex into surrounding soft tissues. 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the flow-perfusion scaffold format for Ewing sarcoma drug-sensitivity modeling."],"evidence_status":"Evidence recorded","metadata_completeness":90,"metadata_present":["Model category","NAMO class","Organism","Cell type","Cell source","Culture system","Modeled mechanism","Publication","Evidence"],"metadata_missing":["Anatomy"],"dataset_context":"Available in same 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others do not, which localises the limiting problem to redox balance.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:30429455","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30429455","reference_title":"Rescue from galactose-induced death of Leigh Syndrome patient cells by pyruvate and NAD().","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"LS cell death was dose-dependently inhibited by pyruvate, malate, oxaloacetate, α-ketoglutarate, aspartate, and exogenous NAD+ (eNAD), but not by lactate, succinate, α-ketobutyrate, and uridine.","explanation":"The rescue profile, including the substrates that did not work, which is what makes the interpretation specific."}],"notes":null}],"evidence":[{"reference":"PMID:30429455","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30429455","reference_title":"Rescue from galactose-induced death of Leigh Syndrome patient cells by pyruvate and NAD().","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"These cell lines harbored mutations in nuclear DNA (nDNA)-encoded CI genes (NDUFS7, NDUFS8, NDUFV1) and, to prevent glycolysis upregulation, were cultured in a pyruvate-free medium in which glucose was replaced by galactose.","explanation":"Confirms an NDUFS7 line is in the panel and states the design choice that makes the model informative."},{"reference":"PMID:30429455","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30429455","reference_title":"Rescue from galactose-induced death of Leigh Syndrome patient cells by pyruvate and NAD().","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Following optimization of the cell culture protocol, LS fibroblasts died in the galactose medium, whereas control cells did not.","explanation":"The survival measurement behind this readout."},{"reference":"PMID:30429455","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30429455","reference_title":"Rescue from galactose-induced death of Leigh Syndrome patient cells by pyruvate and NAD().","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"LS cell death was dose-dependently inhibited by pyruvate, malate, oxaloacetate, α-ketoglutarate, aspartate, and exogenous NAD+ (eNAD), but not by lactate, succinate, α-ketobutyrate, and uridine.","explanation":"The rescue profile, including the substrates that did not work, which is what makes the interpretation specific."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Mitochondrial_Complex_I_Deficiency_Nuclear_Type_3","model_node_id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_3.yaml:Galactose-stressed Leigh syndrome patient fibroblasts (NDUFS7 line)","focus_node_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_3:pathophysiology:Isolated%20Complex%20I%20Deficiency%20and%20Bioenergetic%20Failure","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_3.html#pathograph","nodes":[{"id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_3.yaml:Galactose-stressed Leigh syndrome patient fibroblasts (NDUFS7 line)","kind":"experimental_model","kind_label":"NAM model","label":"Galactose-stressed Leigh syndrome patient fibroblasts (NDUFS7 line)","description":"Patient fibroblasts, including a line carrying the founding NDUFS7 allele, cultured in a pyruvate-free medium with galactose substituted for glucose so that glycolytic compensation cannot mask the bioenergetic deficit. 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Both arms of the module node are evidenced here rather than only one: an NDUFS7-containing fibroblast panel shows raised ROS alongside reduced complex I activity and amount, and an engineered NDUFS7 mutation in HEK293T cells produces reduced proliferation, elevated cell death and increased susceptibility to oxidative stress.\nTwo caveats a curator should carry forward. First, cultured cells hide the deficit: complex I-deficient cells upregulate glycolysis to replace the lost mitochondrial ATP, and that adaptation masks other consequences - which is why the NDUFS7 line only dies when glucose is replaced by galactose in a pyruvate-free medium. The clinical counterpart is decompensation under catabolic stress. Second, the cells are not defenceless: upregulated SLC7A11 imports cystine and raises glutathione, and that response measurably limits the cell death caused by NDUFS7 deficiency.\nConformance note: the module's upstream node - age-related mitochondrial damage and mtDNA mutation - does not apply to a primary nuclear-gene subunit defect, so conformance is declared at this node alone.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_3.html#pathophysiology-isolated-complex-i-deficiency-and-bioenergetic-failure","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_3:pathophysiology:Basal%20Ganglia%20and%20Brainstem%20Vulnerability","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Basal Ganglia and Brainstem Vulnerability","description":"Selective failure of the basal ganglia, midbrain and brainstem, producing the bilateral symmetrical T2-hyperintense lesions that define Leigh syndrome. It is the anatomical signature of this entity: the founding siblings had neuropathologically proven Leigh syndrome, the Finnish siblings showed early basal ganglia and midbrain involvement, and the canine model reproduces both the imaging pattern and the underlying encephalomalacia.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_3.html#pathophysiology-basal-ganglia-and-brainstem-vulnerability","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_3:pathophysiology:Defective%20NADH-to-Ubiquinone%20Electron%20Transfer","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Defective NADH-to-Ubiquinone Electron Transfer","description":"The measured biochemical endpoint: reduced NADH:ubiquinone oxidoreductase activity, with the rest of the respiratory chain intact. Reconstructing the patient V122M substitution in the homologous subunit of Yarrowia lipolytica halves Vmax, and the same experiment records altered Km for n-decyl-ubiquinone and altered I50 for hydrophobic complex I inhibitors - both quinone-site readouts. The authors take this as evidence that nuclear-coded subunits, not only the hydrophobic mitochondrially coded ones, participate in the reaction with ubiquinone, which is precisely the claim the upstream Q-module node makes structurally.\nThe fibroblast panel that includes an NDUFS7 line adds the amount-versus-activity decomposition: in controls the ratio of complex I activity to complex I amount is one, and in patients it is below one, so the enzyme that does assemble is intrinsically less catalytically competent. The deficiency is quantitative and qualitative at once, which is what a core Q-module subunit defect predicts.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_3.html#pathophysiology-defective-nadh-to-ubiquinone-electron-transfer","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_3:pathophysiology:Retinal%20Ganglion%20Cell%20and%20Optic%20Nerve%20Vulnerability","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Retinal Ganglion Cell and Optic Nerve Vulnerability","description":"The other end of the tissue spectrum, and the newer of the two. 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The mechanistic proposal for why the same gene should do two different things is curated separately as a hypothesis.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_3.html#pathophysiology-retinal-ganglion-cell-and-optic-nerve-vulnerability","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"}],"edges":[{"id":"model-link:0:model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_3.yaml:Galactose-stressed Leigh syndrome patient fibroblasts (NDUFS7 line)","source_id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_3.yaml:Galactose-stressed Leigh syndrome patient fibroblasts (NDUFS7 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survival in galactose, pyruvate-free medium","Rescue of galactose-induced death by NAD+-regenerating substrates"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:30429455","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30429455","reference_title":"Rescue from galactose-induced death of Leigh Syndrome patient cells by pyruvate and NAD().","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"These cell lines harbored mutations in nuclear DNA (nDNA)-encoded CI genes (NDUFS7, NDUFS8, NDUFV1) and, to prevent glycolysis upregulation, were cultured in a pyruvate-free medium in which glucose was replaced by galactose.","explanation":"Confirms an NDUFS7 line is in the panel and states the design choice that makes the model 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It is a conditional model - in ordinary glucose medium the same cells survive.","notes":null,"context_id":"disorder:Mitochondrial_Complex_I_Deficiency_Nuclear_Type_2","context_kind":"Disorder","disease_name":"Mitochondrial Complex I Deficiency, Nuclear Type 2","disease_synonyms":["MC1DN2","NDUFS8 deficiency","mitochondrial complex I deficiency, nuclear type 2","TYKY subunit deficiency","complex I deficiency due to NDUFS8 mutation"],"disease_term":{"id":"MONDO:0032606","label":"mitochondrial complex I deficiency, nuclear type 2","display_label":"mitochondrial complex I deficiency, nuclear type 2","url":"http://purl.obolibrary.org/obo/MONDO_0032606"},"experimental_model_type":"PRIMARY_CELL_CULTURE","experimental_model_type_label":"Primary-cell culture","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},"organism_label":"Homo sapiens","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[{"id":"CL:0000057","label":"fibroblast","display_label":"Fibroblast","url":"http://purl.obolibrary.org/obo/CL_0000057"}],"model_cell_type_labels":["fibroblast"],"linked_cell_types":[{"id":"CL:0000057","label":"fibroblast","display_label":"Fibroblast","url":"http://purl.obolibrary.org/obo/CL_0000057"}],"linked_cell_type_labels":["fibroblast"],"cell_types":[{"id":"CL:0000057","label":"fibroblast","display_label":"Fibroblast","url":"http://purl.obolibrary.org/obo/CL_0000057"}],"cell_type_labels":["fibroblast"],"conditions":[],"cell_source":null,"source_category":"Primary / biopsy-derived","culture_system":null,"publication":"PMID:30429455","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/30429455","mechanisms":[{"target":"Glycolytic Compensation Masking the Bioenergetic Deficit","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_2.html#pathophysiology-glycolytic-compensation-masking-the-bioenergetic-deficit","relationship":"MEASURES","relationship_label":"Measures","fidelity":"MODERATE","fidelity_label":"Moderate","description":"The galactose switch is a direct assay of the compensation node: it removes the glycolytic route and measures what is left.","limitations":"Fibroblasts are not the affected tissue - the disease kills neurons and the striatum, not skin - and forced galactose metabolism is a supraphysiological stress with no in vivo counterpart. The lines pool three different genes, so an NDUFS8-specific effect cannot be separated from a general complex I one in this design. A modelling review identifies the NDUFS8 line in this experiment as carrying p.Arg94Cys, which at least anchors which allele was represented.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[{"id":"CL:0000057","label":"fibroblast","display_label":"Fibroblast","url":"http://purl.obolibrary.org/obo/CL_0000057"}],"biological_processes":[],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Survival in galactose medium","description":null,"target":"Glycolytic Compensation Masking the Bioenergetic Deficit","direction":"DECREASED","interpretation":"Patient cells die where controls survive, showing the deficit is lethal once glycolysis cannot compensate.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:30429455","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30429455","reference_title":"Rescue from galactose-induced death of Leigh Syndrome patient cells by pyruvate and NAD().","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Following optimization of the cell culture protocol, LS fibroblasts died in the galactose medium, whereas control cells did not.","explanation":"The survival readout, with the control comparison."}],"notes":null}],"evidence":[{"reference":"PMID:30429455","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30429455","reference_title":"Rescue from galactose-induced death of Leigh Syndrome patient cells by pyruvate and NAD().","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Cell models of mitochondrial complex I (CI) deficiency display activation of glycolysis to compensate for the loss in mitochondrial ATP production. 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It is a conditional model - in ordinary glucose medium the same cells survive.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_2.html#experimental-model-galactose-stressed-leigh-syndrome-patient-fibroblasts-ndufs7-ndufs8-ndufv1","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_2:pathophysiology:Impaired%20NADH-Ubiquinone%20Oxidoreduction%20and%20OXPHOS%20Deficit","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired NADH-Ubiquinone Oxidoreduction and OXPHOS Deficit","description":"Reduced NADH oxidation and electron delivery to ubiquinone lower proton pumping and oxidative phosphorylation capacity. 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Cells with complex I deficiency upregulate glycolysis to replace lost mitochondrial ATP, and that adaptation masks other consequences of the deficiency. Replacing glucose with galactose in a pyruvate-free medium removes the glycolytic escape route: under those conditions patient fibroblasts die while control cells do not.\nClinically the same logic explains why these patients decompensate under catabolic stress, and why a resting biochemical measurement can understate how close to the edge a tissue is.\nGlycolysis is not the only compensatory response in play. In the late-onset patient's skeletal muscle the mitochondrially encoded complex IV COI subunit was ELEVATED while complex I protein was reduced, which the reporting authors read as an attempt to compensate by inducing mitochondrial gene expression. That is hedged as a reading rather than a demonstration, but it is worth recording: an assay that finds one respiratory complex up and another down should not be assumed to have gone wrong.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_2.html#pathophysiology-glycolytic-compensation-masking-the-bioenergetic-deficit","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_2:pathophysiology:Increased%20Reactive%20Oxygen%20Species%20Production","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Increased Reactive Oxygen Species Production","description":"Fibroblasts from children with nuclear complex I gene defects, including NDUFS8, show raised reactive oxygen species. 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The reporting authors read that as evidence that complex I expression is itself regulated by ROS, which makes this node a feedback modifier on the assembly node rather than a terminal consequence.\nIt is curated PROVISIONAL because the causal claim rests on the correlated response to one intervention in cultured fibroblasts, and because the authors describe the contribution of ROS to pathogenesis as supported by circumstantial evidence.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_2.html#pathophysiology-increased-reactive-oxygen-species-production","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_2:pathophysiology:Leigh%20Syndrome%20and%20Mitochondrial%20Encephalomyopathy","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Leigh Syndrome and Mitochondrial Encephalomyopathy","description":"The clinical endpoint, and the striking thing about it in this entity is its range rather than its severity. 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The authors of that report make the methodological point explicitly: untargeted exome analysis can re-write a phenotype.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_2.html#pathophysiology-leigh-syndrome-and-mitochondrial-encephalomyopathy","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_2:pathophysiology:Reduced%20Complex%20I%20Amount%20and%20Intrinsic%20Catalytic%20Activity","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced Complex I Amount and Intrinsic Catalytic Activity","description":"The step at which this entity's biochemistry says something the assembly story alone does not. In control fibroblasts the ratio between complex I enzymatic activity and complex I amount is exactly one - enzyme present is enzyme working. In fibroblasts from children with nuclear complex I gene defects including NDUFS8 that ratio falls below one. The enzyme that does get assembled is therefore intrinsically impaired, not merely scarce.\nThat is what a core subunit carrying the terminal iron-sulfur cluster would be expected to do, and it distinguishes this entity mechanistically from the accessory-subunit deficiencies elsewhere in the nuclear complex I series, where the lesion is essentially one of quantity. Practically, it also predicts a ceiling on any therapy that works by increasing the amount of complex I - see the antioxidant node.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_2.html#pathophysiology-reduced-complex-i-amount-and-intrinsic-catalytic-activity","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"}],"edges":[{"id":"model-link:1:model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_2.yaml:Galactose-stressed Leigh syndrome patient fibroblasts (NDUFS7/NDUFS8/NDUFV1)","source_id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_2.yaml:Galactose-stressed Leigh syndrome patient fibroblasts 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This adaptation can mask other relevant deficiency-induced aberrations in cell physiology.","explanation":"States why the model is constructed this way, which is what makes it informative for this node."},{"reference":"PMID:30429455","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30429455","reference_title":"Rescue from galactose-induced death of Leigh Syndrome patient cells by pyruvate and NAD().","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Following optimization of the cell culture protocol, LS fibroblasts died in the galactose medium, whereas control cells did not.","explanation":"The survival readout, with the control comparison."},{"reference":"PMID:30429455","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30429455","reference_title":"Rescue from galactose-induced death of Leigh Syndrome patient cells by pyruvate and NAD().","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"These findings establish a cell-based strategy for intervention testing and enhance our understanding of CI deficiency pathophysiology.","explanation":"The authors' own statement of what the model is informative for."},{"reference":"PMID:39385390","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39385390","reference_title":"Disease models of Leigh syndrome: From yeast to organoids.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"used three of the previously studied patient fibroblasts carrying mutations in NDUFS7-p.V112M, NDUFS8-p.R94C, and NDUFV1-p.R59X/p.T423M","explanation":"Names the exact NDUFS8 allele represented in the galactose experiment, which the primary report does not spell out."},{"reference":"PMID:30429455","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30429455","reference_title":"Rescue from galactose-induced death of Leigh Syndrome patient cells by pyruvate and NAD().","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Functionally, in LS cells glucose-by-galactose replacement increased mitochondrial fragmentation and mass, depolarized the mitochondrial membrane potential","explanation":"Records the depolarization measurement."},{"reference":"PMID:30429455","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30429455","reference_title":"Rescue from galactose-induced death of Leigh Syndrome patient cells by pyruvate and NAD().","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"LS cell death was dose-dependently inhibited by pyruvate, malate, oxaloacetate, α-ketoglutarate, aspartate, and exogenous NAD+ (eNAD), but not by lactate, succinate, α-ketobutyrate, and uridine.","explanation":"The differential rescue profile behind this readout."}],"evidence_text":["Cell models of mitochondrial complex I (CI) deficiency display activation of glycolysis to compensate for the loss in mitochondrial ATP production. 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Conditional Gas2l2 deletion impairs clearance in mice, supporting a transport consequence without establishing that every normal-TEM PCD genotype shares this mechanism.","url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Ciliary_Dyskinesia.html#pathophysiology-ciliary-disorientation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APrimary_Ciliary_Dyskinesia:pathophysiology:Impaired%20Mucociliary%20Clearance","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Mucociliary Clearance","description":"Ineffective propulsion by airway cilia, insufficient cilia number and impaired epithelial transport retain mucus and inhaled material. Radioaerosol clearance was absent in most of 69 measured patients spanning 26 genotypes, with a residual-clearance exception in CCDC103-related disease. Voluntary cough improved clearance and represents a partly compensating mechanism; regional deposition and cough complicate interpretation of whole-lung tracer measurements.","url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Ciliary_Dyskinesia.html#pathophysiology-impaired-mucociliary-clearance","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Primary_Ciliary_Dyskinesia.yaml:GAS2L2-deficient patient nasal epithelial orientation model","source_id":"model:kb/disorders/Primary_Ciliary_Dyskinesia.yaml:GAS2L2-deficient patient nasal epithelial orientation model","target_id":"node:disorder%3APrimary_Ciliary_Dyskinesia:pathophysiology:Ciliary%20Disorientation","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"Measures patient-associated ciliary disorientation together with asynchronous, increased-frequency beating.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3APrimary_Ciliary_Dyskinesia:2:0","source_id":"node:disorder%3APrimary_Ciliary_Dyskinesia:pathophysiology:Ciliary%20Disorientation","target_id":"node:disorder%3APrimary_Ciliary_Dyskinesia:pathophysiology:Impaired%20Mucociliary%20Clearance","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[0]","label":"Indirectly causes (known intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_KNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Known Intermediates","description":"Loss of common ciliary orientation can reduce effective directional transport; 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this does not establish the cause of transport failure in C1d-associated disease."}],"evidence_text":["Cultured GAS2L2-deficient nasal epithelial cells from one of the affected individuals showed defects in ciliary orientation and had an asynchronous and hyperkinetic (GAS2L2-deficient = 19.8 Hz versus control = 15.8 Hz) ciliary-beat pattern.","Patient-derived nasal cells demonstrate an orientation defect with asynchronous hyperkinetic beating; this does not establish the cause of transport failure in C1d-associated disease."],"evidence_status":"Evidence recorded","metadata_completeness":100,"metadata_present":["Model category","NAMO class","Organism","Anatomy","Cell type","Cell source","Culture system","Modeled mechanism","Publication","Evidence"],"metadata_missing":[],"dataset_context":"Available in same entry","context_dataset_ids":["dataset:geo:gse254100","dataset:geo:gse272189"],"candidate_dataset_ids":[],"source_path":"kb/disorders/Primary_Ciliary_Dyskinesia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Primary_Ciliary_Dyskinesia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Ciliary_Dyskinesia.html#experimental-model-gas2l2-deficient-patient-nasal-epithelial-orientation-model","source_anchor":"experimental-model-gas2l2-deficient-patient-nasal-epithelial-orientation-model"},{"id":"model:kb/disorders/Combined_Oxidative_Phosphorylation_Deficiency_42.yaml:GATC patient primary dermal fibroblasts","name":"GATC patient primary dermal fibroblasts","description":"Primary skin fibroblasts from patient P4B, homozygous for GATC p.Met78Arg. They are the system in which nearly all the mechanism in this entry was established, and they are also the clearest illustration of why fibroblasts are a poor diagnostic tissue for this disorder: under standard culture conditions their respiratory chain enzymes and steady-state OXPHOS subunit levels are normal, and the defect appears only when glutamine is withdrawn or translational demand is sustained.","notes":null,"context_id":"disorder:Combined_Oxidative_Phosphorylation_Deficiency_42","context_kind":"Disorder","disease_name":"Combined oxidative phosphorylation deficiency 42","disease_synonyms":["COXPD42","GATC-related mitochondrial cardiomyopathy","GatC deficiency"],"disease_term":{"id":"MONDO:0030008","label":"combined oxidative phosphorylation deficiency 42","display_label":"Combined oxidative phosphorylation deficiency 42","url":"http://purl.obolibrary.org/obo/MONDO_0030008"},"experimental_model_type":"PRIMARY_CELL_CULTURE","experimental_model_type_label":"Primary-cell culture","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":null,"source_category":"Primary / biopsy-derived","culture_system":null,"publication":null,"publication_url":null,"mechanisms":[{"target":"GatCAB Trimer Destabilization","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_oxidative_phosphorylation_deficiency_42.html#pathophysiology-gatcab-trimer-destabilization","relationship":"MEASURES","relationship_label":"Measures","fidelity":"HIGH","fidelity_label":"High","description":"The system in which GatC depletion to 20 percent of control, the parallel loss of GatA and GatB, and the unchanged transcript levels were measured.","limitations":"Fibroblast is not the affected tissue. Whether the same degree of subunit depletion occurs in cardiomyocytes has not been measured.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[],"biological_processes":[],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"GatC steady-state protein level","description":null,"target":"GatCAB Trimer Destabilization","direction":"DECREASED","interpretation":"Reduction to about a fifth of control, with GatA and GatB falling in parallel, is the measurement establishing trimer destabilization.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:30283131","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30283131","reference_title":"Pathogenic variants in glutamyl-tRNA(Gln) amidotransferase subunits cause a lethal mitochondrial cardiomyopathy disorder.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Western blot analysis of control and patient P4B fibroblasts showed a strong reduction in GatC protein, and also reduced levels of GatA and GatB protein, with porin as loading control.","explanation":"The western blot measurement underlying this readout."}],"notes":null}],"evidence":[{"reference":"PMID:30283131","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30283131","reference_title":"Pathogenic variants in glutamyl-tRNA(Gln) amidotransferase subunits cause a lethal mitochondrial cardiomyopathy disorder.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"In subject P4B with mutations in GATC, the steady state level of GatC in fibroblasts was decreased to 20% of controls","explanation":"Establishes the model as informative for the trimer-destabilization node."},{"reference":"PMID:30283131","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30283131","reference_title":"Pathogenic variants in glutamyl-tRNA(Gln) amidotransferase subunits cause a lethal mitochondrial cardiomyopathy disorder.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Western blot analysis of control and patient P4B fibroblasts showed a strong reduction in GatC protein, and also reduced levels of GatA and GatB protein, with porin as loading control.","explanation":"The western blot measurement underlying this readout."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Combined_Oxidative_Phosphorylation_Deficiency_42","model_node_id":"model:kb/disorders/Combined_Oxidative_Phosphorylation_Deficiency_42.yaml:GATC patient primary dermal fibroblasts","focus_node_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_42:pathophysiology:GatCAB%20Trimer%20Destabilization","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_oxidative_phosphorylation_deficiency_42.html#pathograph","nodes":[{"id":"model:kb/disorders/Combined_Oxidative_Phosphorylation_Deficiency_42.yaml:GATC patient primary dermal fibroblasts","kind":"experimental_model","kind_label":"NAM model","label":"GATC patient primary dermal fibroblasts","description":"Primary skin fibroblasts from patient P4B, homozygous for GATC p.Met78Arg. 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The patient data show that this architectural role is what fails. In GATC patient fibroblasts GatC protein falls to about 20 percent of control, and GatA and GatB fall by a comparable amount - even though neither of their genes is mutated. The likely explanation is that the individual subunits are unstable when not incorporated into the trimer.\nCrucially this is post-transcriptional: mRNA levels of QRSL1, GATB and GATC were unchanged in patient fibroblasts, so the loss of GatA and GatB is protein instability rather than a transcriptional response. A GATC lesion therefore behaves as a lesion of the whole amidotransferase, which is why a subunit with no catalytic activity of its own produces the same disease as the catalytic subunits.","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_oxidative_phosphorylation_deficiency_42.html#pathophysiology-gatcab-trimer-destabilization","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_42:pathophysiology:Biallelic%20GATC%20Missense%20Variant","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Biallelic GATC Missense Variant","description":"The initiating lesion is the homozygous GATC missense allele c.233T>G (p.Met78Arg), the only GATC variant reported in this disorder. That it is a missense rather than a null allele is not incidental. Complete loss of a tRNA-charging function is thought to be embryonically lethal, so a viable patient must retain some residual activity; every patient in the defining series carried at least one missense allele. The authors go further and propose that severity tracks the degree of conservation of the affected residue - the prenatal-onset GATB and QRSL1 families had variants at highly conserved residues, while the infantile-onset GATC families had a variant at a moderately conserved one. On that reading the later onset of COXPD42 relative to its GatCAB siblings is a consequence of a milder residual activity, not of the subunit affected.","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_oxidative_phosphorylation_deficiency_42.html#pathophysiology-biallelic-gatc-missense-variant","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_42:pathophysiology:Impaired%20Transamidation%20of%20Glu-mt-tRNA%28Gln%29","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Transamidation of Glu-mt-tRNA(Gln)","description":"Mitochondria have no glutaminyl-tRNA synthetase. Glutaminyl mt-tRNA is therefore charged indirectly in two steps: EARS2 mischarges it with glutamate, and GatCAB transamidates the Glu-mt-tRNA(Gln) to Gln-mt-tRNA(Gln) using free glutamine as amide donor. The same paper closed the obvious escape route - cytoplasmic QARS had been reported in some databases as dual-localised, but QARS-GFP did not co-localise with TOM20, cellular fractionation showed no mitochondrial enrichment, and the trace that did fractionate with mitochondria was proteinase-K sensitive. Mitochondria depend exclusively on GatCAB.\nThe defect is conditional on substrate supply, which is the single most important practical fact about this disorder. In standard glutamine-rich culture medium patient fibroblasts charge mt-tRNA(Gln) similarly to controls; only after three days without glutamine does charging fall. A normal-looking fibroblast assay run under standard conditions is therefore not evidence against the diagnosis.","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_oxidative_phosphorylation_deficiency_42.html#pathophysiology-impaired-transamidation-of-glu-mt-trna-gln","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"}],"edges":[{"id":"model-link:0:model:kb/disorders/Combined_Oxidative_Phosphorylation_Deficiency_42.yaml:GATC patient primary dermal fibroblasts","source_id":"model:kb/disorders/Combined_Oxidative_Phosphorylation_Deficiency_42.yaml:GATC patient primary dermal fibroblasts","target_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_42:pathophysiology:GatCAB%20Trimer%20Destabilization","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Measures","directed":false,"relationship":"MEASURES","fidelity":"HIGH","causal_link_type":null,"causal_link_type_label":null,"description":"The system in which GatC depletion to 20 percent of control, the parallel loss of GatA and GatB, and the unchanged transcript levels were measured.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_42:0:0","source_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_42:pathophysiology:Biallelic%20GATC%20Missense%20Variant","target_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_42:pathophysiology:GatCAB%20Trimer%20Destabilization","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_42:1:0","source_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_42:pathophysiology:GatCAB%20Trimer%20Destabilization","target_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_42:pathophysiology:Impaired%20Transamidation%20of%20Glu-mt-tRNA%28Gln%29","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0}]}},{"target":"Impaired Transamidation of Glu-mt-tRNA(Gln)","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_oxidative_phosphorylation_deficiency_42.html#pathophysiology-impaired-transamidation-of-glu-mt-trna-gln","relationship":"PARTIALLY_RECAPITULATES","relationship_label":"Partially Recapitulates","fidelity":"MODERATE","fidelity_label":"Moderate","description":"Reproduces the charging defect, but conditionally: mt-tRNA(Gln) charging is similar to control in glutamine-replete medium and falls only after three days of glutamine withdrawal.","limitations":"The conditionality is the limitation. A negative result in glutamine-replete medium says nothing about the genotype, so this model must be run under glutamine restriction to be informative.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[],"biological_processes":[],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"mt-tRNA(Gln) aminoacylation by northern blot","description":null,"target":"Impaired Transamidation of Glu-mt-tRNA(Gln)","direction":"DECREASED","interpretation":"Reduced charging under glutamine withdrawal, against normal charging in replete medium.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:30283131","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30283131","reference_title":"Pathogenic variants in glutamyl-tRNA(Gln) amidotransferase subunits cause a lethal mitochondrial cardiomyopathy disorder.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"After 3 days in culture medium without glutamine, fibroblasts from P1A, P3A, and P4B show decreased glutamine charging of mt-tRNAGln compared to control fibroblasts.","explanation":"The northern blot measurement underlying this readout."}],"notes":null}],"evidence":[{"reference":"PMID:30283131","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30283131","reference_title":"Pathogenic variants in glutamyl-tRNA(Gln) amidotransferase subunits cause a lethal mitochondrial cardiomyopathy disorder.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"While aminoacylation of mt-tRNAGln appears to show only minor changes in comparison to controls when patient cells are grown under standard conditions with high concentrations of the GatCAB substrate glutamine in the culture medium","explanation":"Curated as PARTIAL because the model reproduces the defect only under glutamine restriction."},{"reference":"PMID:30283131","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30283131","reference_title":"Pathogenic variants in glutamyl-tRNA(Gln) amidotransferase subunits cause a lethal mitochondrial cardiomyopathy disorder.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"After 3 days in culture medium without glutamine, fibroblasts from P1A, P3A, and P4B show decreased glutamine charging of mt-tRNAGln compared to control fibroblasts.","explanation":"The northern blot measurement underlying this readout."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Combined_Oxidative_Phosphorylation_Deficiency_42","model_node_id":"model:kb/disorders/Combined_Oxidative_Phosphorylation_Deficiency_42.yaml:GATC patient primary dermal fibroblasts","focus_node_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_42:pathophysiology:Impaired%20Transamidation%20of%20Glu-mt-tRNA%28Gln%29","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_oxidative_phosphorylation_deficiency_42.html#pathograph","nodes":[{"id":"model:kb/disorders/Combined_Oxidative_Phosphorylation_Deficiency_42.yaml:GATC patient primary dermal fibroblasts","kind":"experimental_model","kind_label":"NAM model","label":"GATC patient primary dermal fibroblasts","description":"Primary skin fibroblasts from patient P4B, homozygous for GATC p.Met78Arg. They are the system in which nearly all the mechanism in this entry was established, and they are also the clearest illustration of why fibroblasts are a poor diagnostic tissue for this disorder: under standard culture conditions their respiratory chain enzymes and steady-state OXPHOS subunit levels are normal, and the defect appears only when glutamine is withdrawn or translational demand is sustained.","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_oxidative_phosphorylation_deficiency_42.html#experimental-model-gatc-patient-primary-dermal-fibroblasts","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_42:pathophysiology:Impaired%20Transamidation%20of%20Glu-mt-tRNA%28Gln%29","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Transamidation of Glu-mt-tRNA(Gln)","description":"Mitochondria have no glutaminyl-tRNA synthetase. 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A normal-looking fibroblast assay run under standard conditions is therefore not evidence against the diagnosis.","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_oxidative_phosphorylation_deficiency_42.html#pathophysiology-impaired-transamidation-of-glu-mt-trna-gln","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_42:pathophysiology:Deficient%20Mitochondrial%20Protein%20Synthesis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Deficient Mitochondrial Protein Synthesis","description":"Pulse labelling with radiolabelled methionine in the presence of emetine, to silence cytoplasmic translation, showed a strong and generalized defect in mtDNA-encoded protein synthesis in the GATC patient's fibroblasts. 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A chloramphenicol block and release experiment made the kinetics visible: translation resumes at a near-normal rate for a few hours on accumulated charged tRNA, then falls behind as charging fails to keep up with demand.","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_oxidative_phosphorylation_deficiency_42.html#pathophysiology-deficient-mitochondrial-protein-synthesis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_42:pathophysiology:GatCAB%20Trimer%20Destabilization","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"GatCAB Trimer Destabilization","description":"In the bacterial complex GatA carries the amidase function and GatB the kinase function, while GatC serves as a stabilizing linker between them. 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A GATC lesion therefore behaves as a lesion of the whole amidotransferase, which is why a subunit with no catalytic activity of its own produces the same disease as the catalytic subunits.","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_oxidative_phosphorylation_deficiency_42.html#pathophysiology-gatcab-trimer-destabilization","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"}],"edges":[{"id":"model-link:1:model:kb/disorders/Combined_Oxidative_Phosphorylation_Deficiency_42.yaml:GATC patient primary dermal fibroblasts","source_id":"model:kb/disorders/Combined_Oxidative_Phosphorylation_Deficiency_42.yaml:GATC patient primary dermal fibroblasts","target_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_42:pathophysiology:Impaired%20Transamidation%20of%20Glu-mt-tRNA%28Gln%29","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[1]","label":"Partially Recapitulates","directed":false,"relationship":"PARTIALLY_RECAPITULATES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"Reproduces the charging defect, but conditionally: mt-tRNA(Gln) charging is similar to control in glutamine-replete medium and falls only after three days of glutamine withdrawal.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_42:1:0","source_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_42:pathophysiology:GatCAB%20Trimer%20Destabilization","target_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_42:pathophysiology:Impaired%20Transamidation%20of%20Glu-mt-tRNA%28Gln%29","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_42:2:0","source_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_42:pathophysiology:Impaired%20Transamidation%20of%20Glu-mt-tRNA%28Gln%29","target_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_42:pathophysiology:Deficient%20Mitochondrial%20Protein%20Synthesis","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0}]}},{"target":"Deficient Mitochondrial Protein Synthesis","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_oxidative_phosphorylation_deficiency_42.html#pathophysiology-deficient-mitochondrial-protein-synthesis","relationship":"RECAPITULATES","relationship_label":"Recapitulates","fidelity":"HIGH","fidelity_label":"High","description":"Radiolabelled-methionine pulse labelling under emetine block showed a strong generalized mtDNA-encoded translation defect in these cells, and a chloramphenicol block-and-release experiment resolved its kinetics.","limitations":"The translation defect does not translate into reduced steady-state OXPHOS subunit levels in this cell type, because the existing subunits are stabilised - so the model reproduces the primary defect but not its usual downstream readout.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0032543","label":"mitochondrial translation","display_label":"mitochondrial translation","url":"http://purl.obolibrary.org/obo/GO_0032543"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"De novo mtDNA-encoded protein synthesis","description":null,"target":"Deficient Mitochondrial Protein Synthesis","direction":"DECREASED","interpretation":"Reduced incorporation of labelled methionine into mitochondrially translated peptides.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:30283131","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30283131","reference_title":"Pathogenic variants in glutamyl-tRNA(Gln) amidotransferase subunits cause a lethal mitochondrial cardiomyopathy disorder.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"a Decrease in newly synthesized peptides in GATA and GATC patient fibroblasts compared to control as determined by pulse labeling.","explanation":"The pulse-labelling measurement underlying this readout. Note the figure legend writes \"GATA\" where the gene is QRSL1 (GatA); the GATC arm is the one relevant here."}],"notes":null}],"evidence":[{"reference":"PMID:30283131","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30283131","reference_title":"Pathogenic variants in glutamyl-tRNA(Gln) amidotransferase subunits cause a lethal mitochondrial cardiomyopathy disorder.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"revealed a strong and generalized mtDNA-encoded protein synthesis defect after a 90-min pulse in P4B (GATC) and in P3A (QRSL1) patients' fibroblasts","explanation":"Establishes the model as informative for the translation node."},{"reference":"PMID:30283131","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30283131","reference_title":"Pathogenic variants in glutamyl-tRNA(Gln) amidotransferase subunits cause a lethal mitochondrial cardiomyopathy disorder.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"a Decrease in newly synthesized peptides in GATA and GATC patient fibroblasts compared to control as determined by pulse labeling.","explanation":"The pulse-labelling measurement underlying this readout. Note the figure legend writes \"GATA\" where the gene is QRSL1 (GatA); the GATC arm is the one relevant here."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Combined_Oxidative_Phosphorylation_Deficiency_42","model_node_id":"model:kb/disorders/Combined_Oxidative_Phosphorylation_Deficiency_42.yaml:GATC patient primary dermal fibroblasts","focus_node_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_42:pathophysiology:Deficient%20Mitochondrial%20Protein%20Synthesis","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_oxidative_phosphorylation_deficiency_42.html#pathograph","nodes":[{"id":"model:kb/disorders/Combined_Oxidative_Phosphorylation_Deficiency_42.yaml:GATC patient primary dermal fibroblasts","kind":"experimental_model","kind_label":"NAM model","label":"GATC patient primary dermal fibroblasts","description":"Primary skin fibroblasts from patient P4B, homozygous for GATC p.Met78Arg. 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The module's upstream node - age-related mitochondrial damage and mtDNA mutation - does not apply to a primary nuclear-gene translation defect, which is why conformance is declared at this node alone.","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_oxidative_phosphorylation_deficiency_42.html#pathophysiology-combined-respiratory-chain-enzyme-deficiency","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_42:pathophysiology:Impaired%20Transamidation%20of%20Glu-mt-tRNA%28Gln%29","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Transamidation of Glu-mt-tRNA(Gln)","description":"Mitochondria have no glutaminyl-tRNA synthetase. 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They established two things that changed the field. The hypoplasia is underpinned by intrinsic cardiomyocyte proliferation and differentiation defects rather than being purely haemodynamic, and the disease is genetically heterogeneous and multigenic rather than attributable to one locus. Similar but milder defects in the right ventricle in these models are the animal counterpart of the late systemic right ventricular failure seen in patients.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypoplastic_Left_Heart_Syndrome.html#experimental-model-genetic-mouse-models-of-hypoplastic-left-heart","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypoplastic_Left_Heart_Syndrome:pathophysiology:Genetic%20lesion%20affecting%20cardiac%20growth%20or%20valvulogenesis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Genetic lesion affecting cardiac growth or valvulogenesis","description":"Variants in cardiac transcription factors, signalling genes, sarcomeric genes, and chromatin regulators contribute to the disease, but not in the way a Mendelian disorder does. Eight independent mouse lines produce the phenotype, the human genetic architecture combines de novo single-gene and copy-number lesions with lower-penetrance and common variation, and no single gene accounts for more than a small fraction of cases. That architecture is itself a mechanistic claim, because it says the phenotype is a convergence point reachable by many routes rather than the readout of one pathway.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypoplastic_Left_Heart_Syndrome.html#pathophysiology-genetic-lesion-affecting-cardiac-growth-or-valvulogenesis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypoplastic_Left_Heart_Syndrome:pathophysiology:Impaired%20cardiomyocyte%20proliferation%20and%20differentiation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired cardiomyocyte proliferation and differentiation","description":"Cardiomyocytes in the developing left ventricle proliferate less and differentiate abnormally, with disorganised sarcomeric architecture and altered mitochondrial maturation. This is what the first genetic mouse model of the disease showed, and it is the node that distinguishes an intrinsically small ventricle from a ventricle that is small because it is unused.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypoplastic_Left_Heart_Syndrome.html#pathophysiology-impaired-cardiomyocyte-proliferation-and-differentiation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypoplastic_Left_Heart_Syndrome:pathophysiology:Obstruction%20to%20left%20heart%20inflow%20or%20outflow","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Obstruction to left heart inflow or outflow","description":"Stenosis or atresia of the mitral or aortic valve. In the evolving form this is present in mid-gestation while the left ventricle is still of adequate size, so the obstruction can be observed before the hypoplasia it is proposed to cause.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypoplastic_Left_Heart_Syndrome.html#pathophysiology-obstruction-to-left-heart-inflow-or-outflow","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:1:model:kb/disorders/Hypoplastic_Left_Heart_Syndrome.yaml:Genetic mouse models of hypoplastic left heart","source_id":"model:kb/disorders/Hypoplastic_Left_Heart_Syndrome.yaml:Genetic mouse models of hypoplastic left 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of 8 independent HLHS mouse lines showed HLHS is genetically heterogeneous and multigenic in etiology.","The findings of similar defects of lesser severity in the right ventricle suggest this could contribute to the heart failure risks in surgically palliated HLHS patients.","Establishes the multigenic architecture from independently derived lines rather than from a single mutant.","Provides the model-organism counterpart of the recessive-variant finding in patients, that the right ventricle is not a normal chamber pressed into abnormal service but is itself affected."],"evidence_status":"Evidence recorded","metadata_completeness":70,"metadata_present":["Model category","Organism","Anatomy","Cell type","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Cell source","Culture system"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Hypoplastic_Left_Heart_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hypoplastic_Left_Heart_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hypoplastic_Left_Heart_Syndrome.html#experimental-model-genetic-mouse-models-of-hypoplastic-left-heart","source_anchor":"experimental-model-genetic-mouse-models-of-hypoplastic-left-heart"},{"id":"model:kb/disorders/Hypertrophic_Cardiomyopathy_3.yaml:Genetically engineered heart tissue expressing TPM1 S215L","name":"Genetically engineered heart tissue expressing TPM1 S215L","description":"Three-dimensional genetically engineered heart tissue expressing the TPM1 S215L variant, used together with molecular-dynamics simulation and a Markov model of thin-filament activation to reclassify a variant of unknown significance as 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The measurable consequences are a left-shift in the calcium dependence of filament sliding, residual actomyosin activity at low calcium, and loss of the normal inhibition of sliding in relaxing conditions. Different alleles reach this end state by different routes - S215L and D219V principally by destabilizing the blocked state, E192K by permitting residual crossbridge activity even while overall calcium sensitivity falls - which is why calcium sensitivity alone is an incomplete description of the lesion.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_3.html#pathophysiology-loss-of-crossbridge-inhibition-and-increased-myofilament-calcium-sensitivity","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_3:pathophysiology:Alpha-Tropomyosin%20Thin%20Filament%20Regulatory%20Defect","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Alpha-Tropomyosin Thin Filament Regulatory Defect","description":"TPM1 encodes alpha-tropomyosin, a rod-shaped coiled-coil dimer that polymerises head-to-tail along the actin thin filament and, in concert with the troponin complex, occupies the blocked, closed, or open azimuthal position that determines whether myosin can engage actin. Disease-associated missense substitutions are scattered along the molecule - in the N-terminal overlap/troponin T binding region (Arg21Leu, Gly3Arg, Glu62Gln, Gln68Arg), in the central period 4/5 region that contacts actin (Asp175Asn, Glu180Gly, Glu192Lys), and in the C-terminal region (Ser215Leu, Asp219Val, Asp254Gly) - and act by altering tropomyosin flexibility, its azimuthal positioning on actin, or its interactions with troponin, rather than by abolishing the protein. This is the primary cardiomyocyte insult of CMH3.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_3.html#pathophysiology-alpha-tropomyosin-thin-filament-regulatory-defect","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_3:pathophysiology:Cardiomyocyte%20Hypercontractility%20and%20Impaired%20Relaxation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Cardiomyocyte Hypercontractility and Impaired Relaxation","description":"At the level of the working myocyte the regulatory defect presents as hypercontractility with a relaxation deficit: three-dimensional engineered heart tissues carrying TPM1 HCM variants generate excess force, relax slowly, and show diastolic dysfunction, together with induction of hypertrophic gene markers and cellular hypertrophy. Patient-derived hiPSC-cardiomyocytes carrying the classic Asp175Asn allele reproduce the cellular phenotype with increased cell size and altered calcium handling and electrophysiology. Hypercontractility is the pathophysiological abnormality that myosin-inhibitor therapy is designed to reverse.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_3.html#pathophysiology-cardiomyocyte-hypercontractility-and-impaired-relaxation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Hypertrophic_Cardiomyopathy_3.yaml:Genetically engineered heart tissue expressing TPM1 S215L","source_id":"model:kb/disorders/Hypertrophic_Cardiomyopathy_3.yaml:Genetically engineered heart tissue expressing TPM1 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Patient-derived hiPSC-cardiomyocytes carrying the classic Asp175Asn allele reproduce the cellular phenotype with increased cell size and altered calcium handling and electrophysiology. Hypercontractility is the pathophysiological abnormality that myosin-inhibitor therapy is designed to reverse.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_3.html#pathophysiology-cardiomyocyte-hypercontractility-and-impaired-relaxation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_3:pathophysiology:Cardiomyocyte%20Hypertrophy%20with%20Myofiber%20Disarray%20and%20Interstitial%20Fibrosis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Cardiomyocyte Hypertrophy with Myofiber Disarray and Interstitial Fibrosis","description":"Sustained hypercontractility and calcium-dependent hypertrophic signaling remodel the myocardium into the classic hypertrophic pattern: myocyte hypertrophy, loss of the normal parallel myofibre architecture (disarray), and replacement/interstitial fibrosis, producing wall thickening with a small cavity. Histology in TPM1-mutation hearts is indistinguishable from that of other sarcomeric causes, so the node is a faithful specialization of the generic ventricular-remodeling node rather than a TPM1-specific pathology. Human cardiac biopsies carrying TPM1 variants show loss of sarcomeric structure.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_3.html#pathophysiology-cardiomyocyte-hypertrophy-with-myofiber-disarray-and-interstitial-fibrosis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_3:pathophysiology:Diastolic%20Dysfunction%20and%20Left%20Ventricular%20Outflow%20Tract%20Obstruction","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Diastolic Dysfunction and Left Ventricular Outflow Tract Obstruction","description":"The stiffened, hypertrophied, fibrotic ventricle fills poorly, and when hypertrophy is asymmetric and septal it can also obstruct the left ventricular outflow tract dynamically. The clinical result is exertional dyspnoea, chest pain, and reduced exercise capacity with preserved or supranormal ejection fraction. Thin-filament HCM as a class tends to produce relatively less hypertrophy and less outflow obstruction than thick-filament HCM while carrying more heart-failure morbidity, so the obstructive presentation should not be assumed in a TPM1 carrier.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_3.html#pathophysiology-diastolic-dysfunction-and-left-ventricular-outflow-tract-obstruction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_3:pathophysiology:Loss%20of%20Crossbridge%20Inhibition%20and%20Increased%20Myofilament%20Calcium%20Sensitivity","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Loss of Crossbridge Inhibition and Increased Myofilament Calcium Sensitivity","description":"Mutant alpha-tropomyosin is more flexible and sits less stably in the inhibitory (blocked/closed) position on actin, so the thin filament fails to keep myosin switched off. The measurable consequences are a left-shift in the calcium dependence of filament sliding, residual actomyosin activity at low calcium, and loss of the normal inhibition of sliding in relaxing conditions. Different alleles reach this end state by different routes - S215L and D219V principally by destabilizing the blocked state, E192K by permitting residual crossbridge activity even while overall calcium sensitivity falls - which is why calcium sensitivity alone is an incomplete description of the lesion.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_3.html#pathophysiology-loss-of-crossbridge-inhibition-and-increased-myofilament-calcium-sensitivity","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:1:model:kb/disorders/Hypertrophic_Cardiomyopathy_3.yaml:Genetically engineered heart tissue expressing TPM1 S215L","source_id":"model:kb/disorders/Hypertrophic_Cardiomyopathy_3.yaml:Genetically engineered heart tissue expressing TPM1 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pathogenic.","evidence":[]}],"findings_text":["Hypercontractility, upregulation of hypertrophic gene markers, and diastolic dysfunction, supporting reclassification of S215L as pathogenic."],"evidence":[{"reference":"PMID:36896133","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/36896133","reference_title":"Mechanisms of pathogenicity in the hypertrophic cardiomyopathy-associated TPM1 variant S215L.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Three-dimensional genetically engineered heart tissues expressing TPM1 S215L exhibited hypercontractility, upregulation of hypertrophic gene markers, and diastolic dysfunction.","explanation":"Describes the model and its phenotype."}],"evidence_text":["Three-dimensional genetically engineered heart tissues expressing TPM1 S215L exhibited hypercontractility, upregulation of hypertrophic gene markers, and diastolic dysfunction.","Describes the model and its phenotype."],"evidence_status":"Evidence 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This system established both that complex assembly is preserved and that H4-tail acetylation on chromatin is lost, and is the functional cornerstone of pathogenicity for the three reported variants.","notes":null,"context_id":"disorder:Neurodevelopmental_Disorder_With_Dysmorphic_Facies_Sleep_Disturbance_And_Brain_Abnormalities","context_kind":"Disorder","disease_name":"Neurodevelopmental Disorder With Dysmorphic Facies, Sleep Disturbance, and Brain Abnormalities","disease_synonyms":["NEDFASB","KAT5-related neurodevelopmental disorder","KAT5-related chromatinopathy","TIP60-related neurodevelopmental syndrome"],"disease_term":{"id":"MONDO:0030852","label":"neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalities","display_label":"neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalities","url":"http://purl.obolibrary.org/obo/MONDO_0030852"},"experimental_model_type":"CELL_LINE","experimental_model_type_label":"Cell line","namo_type":"namo:CellLineModel","declared_namo_class_name":null,"namo_class_name":"CellLineModel","namo_class_label":"Cell Line Model","namo_description":"A model system based on immortalized cell lines that can be maintained in culture indefinitely. Examples: HepG2, A549, Caco-2, etc.","namo_docs_url":"https://monarch-initiative.github.io/namo/elements/CellLineModel/","namo_ontology_url":"https://w3id.org/monarch-initiative/namo/CellLineModel","namo_mapping_basis":"Safe mapping from DisMech category","namo_class_in_schema":true,"namo_schema_status":"Defined in NAMO schema used for this build","modality":"Cellular system","organism":{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},"organism_label":"Homo sapiens","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":null,"source_category":"Immortalized / cell line","culture_system":null,"publication":"PMID:32822602","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32822602","mechanisms":[{"target":"Impaired NuA4/TIP60 Histone H4 Acetyltransferase Activity","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Neurodevelopmental_Disorder_With_Dysmorphic_Facies,_Sleep_Disturbance,_and_Brain_Abnormalities.html#pathophysiology-impaired-nua4-tip60-histone-h4-acetyltransferase-activity","relationship":"MEASURES","relationship_label":"Measures","fidelity":"HIGH","fidelity_label":"High","description":"Purification of native NuA4/TIP60 complexes from cells expressing wild-type or patient-variant KAT5, followed by histone acetylation assays on free histones and on chromatin, is the assay that established both preserved complex assembly and loss of H4-tail acetylation.","limitations":"An erythroleukaemia cell line rather than a neural or neural-crest context, so it reports the biochemical defect faithfully but says nothing about which downstream loci are affected in the tissues that matter.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[],"biological_processes":[],"pathways":[],"genes":[],"chemicals":[],"readouts":[],"evidence":[],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Neurodevelopmental_Disorder_With_Dysmorphic_Facies_Sleep_Disturbance_And_Brain_Abnormalities","model_node_id":"model:kb/disorders/Neurodevelopmental_Disorder_With_Dysmorphic_Facies_Sleep_Disturbance_And_Brain_Abnormalities.yaml:Genome-edited K562 cells expressing patient-variant KAT5","focus_node_id":"node:disorder%3ANeurodevelopmental_Disorder_With_Dysmorphic_Facies_Sleep_Disturbance_And_Brain_Abnormalities:pathophysiology:Impaired%20NuA4%2FTIP60%20Histone%20H4%20Acetyltransferase%20Activity","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Neurodevelopmental_Disorder_With_Dysmorphic_Facies,_Sleep_Disturbance,_and_Brain_Abnormalities.html#pathograph","nodes":[{"id":"model:kb/disorders/Neurodevelopmental_Disorder_With_Dysmorphic_Facies_Sleep_Disturbance_And_Brain_Abnormalities.yaml:Genome-edited K562 cells expressing patient-variant KAT5","kind":"experimental_model","kind_label":"NAM model","label":"Genome-edited K562 cells expressing patient-variant KAT5","description":"K562 cells genome-edited at the AAVS1 locus to express tagged wild-type or patient-variant KAT5 were used to purify native NuA4/TIP60 complexes and quantify histone acetylation on free histones and on chromatin. 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Because complex assembly is preserved, the catalytically dead subunit is expected to occupy complexes that would otherwise contain wild-type KAT5, giving a dominant-interfering effect rather than simple haploinsufficiency.","url":"https://dismech.monarchinitiative.org/pages/disorders/Neurodevelopmental_Disorder_With_Dysmorphic_Facies,_Sleep_Disturbance,_and_Brain_Abnormalities.html#pathophysiology-impaired-nua4-tip60-histone-h4-acetyltransferase-activity","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ANeurodevelopmental_Disorder_With_Dysmorphic_Facies_Sleep_Disturbance_And_Brain_Abnormalities:pathophysiology:Chromatin-Dependent%20Dysregulation%20of%20Developmental%20Transcription","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Chromatin-Dependent Dysregulation of Developmental Transcription","description":"Reduced histone H4 acetylation at NuA4/TIP60 target loci alters chromatin accessibility and RNA polymerase II-dependent transcription. 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PER1 and HDAC4 had previously been mapped as NuA4/TIP60-bound regions, supporting direct rather than incidental dysregulation.","url":"https://dismech.monarchinitiative.org/pages/disorders/Neurodevelopmental_Disorder_With_Dysmorphic_Facies,_Sleep_Disturbance,_and_Brain_Abnormalities.html#pathophysiology-chromatin-dependent-dysregulation-of-developmental-transcription","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ANeurodevelopmental_Disorder_With_Dysmorphic_Facies_Sleep_Disturbance_And_Brain_Abnormalities:pathophysiology:Circadian%20Transcriptional%20Dysregulation%20with%20PER1%20Upregulation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Circadian Transcriptional Dysregulation with PER1 Upregulation","description":"Fibroblasts from affected individuals show upregulated expression of PER1, a core negative-limb component of the transcription-translation feedback loop that generates circadian rhythms, and the authors of the defining report linked this directly to the sleep anomalies seen in all individuals. 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The panel includes p.Gly555Glu, which scores at the low end of enzymatic activity, and the authors attribute its effect to disruption of SDHA-SDHB binding - a full-text derivation recorded in this entry's notes rather than a verified quotation, because the cached reference is abstract-only and names no individual variant.","notes":null,"context_id":"disorder:Dilated_Cardiomyopathy_1GG","context_kind":"Disorder","disease_name":"Dilated Cardiomyopathy 1GG","disease_synonyms":["CMD1GG","cardiomyopathy, dilated, 1GG","dilated cardiomyopathy type 1GG","SDHA familial isolated dilated cardiomyopathy","familial isolated dilated cardiomyopathy caused by mutation in SDHA"],"disease_term":{"id":"MONDO:0013339","label":"dilated cardiomyopathy 1GG","display_label":"dilated cardiomyopathy 1GG","url":"http://purl.obolibrary.org/obo/MONDO_0013339"},"experimental_model_type":"CELL_LINE","experimental_model_type_label":"Cell line","namo_type":"namo:CellLineModel","declared_namo_class_name":null,"namo_class_name":"CellLineModel","namo_class_label":"Cell Line Model","namo_description":"A model system based on immortalized cell lines that can be maintained in culture indefinitely. 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The authors themselves note that activity-score similarity between p.Gly555Glu and an unrelated cancer variant may reflect artefacts of this model system.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0034553","label":"mitochondrial respiratory chain complex II assembly","display_label":"mitochondrial respiratory chain complex II assembly","url":"http://purl.obolibrary.org/obo/GO_0034553"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[],"evidence":[{"reference":"PMID:39321216","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39321216","reference_title":"A Novel Human SDHA-Knockout Cell Line Model for the Functional Analysis of Clinically Relevant SDHA Variants.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"SDHA variants were introduced into a clonal SDHA-knockout cell line via Bxb1-mediated recombination. SDH activity and SDHA abundance were determined for each variant","explanation":"Describes the system and the measurement, which is what makes it informative for the interface node. Scoped to the abstract's account of the assay design; the inclusion of p.Gly555Glu in the panel is a full-text derivation and is not claimed by this snippet."},{"reference":"PMID:39321216","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39321216","reference_title":"A Novel Human SDHA-Knockout Cell Line Model for the Functional Analysis of Clinically Relevant SDHA Variants.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"In total, we characterized 72 variants, developed criteria for obtaining functional evidence, and demonstrated the potential of this evidence for clinical variant interpretation.","explanation":"The scale of the panel, which is the aggregate statement that can be quoted from the cached abstract in support of this variant having been assayed among them."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Dilated_Cardiomyopathy_1GG","model_node_id":"model:kb/disorders/Dilated_Cardiomyopathy_1GG.yaml:HAP1 SDHA-knockout cell line with single-variant reintroduction","focus_node_id":"node:disorder%3ADilated_Cardiomyopathy_1GG:pathophysiology:Destabilised%20Flavoprotein-Iron-Sulfur%20Subunit%20Interface","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy_1GG.html#pathograph","nodes":[{"id":"model:kb/disorders/Dilated_Cardiomyopathy_1GG.yaml:HAP1 SDHA-knockout cell line with single-variant reintroduction","kind":"experimental_model","kind_label":"NAM model","label":"HAP1 SDHA-knockout cell line with single-variant reintroduction","description":"A clonal human SDHA-knockout line into which individual SDHA missense variants are reintroduced by site-specific recombination, after which succinate dehydrogenase activity and SDHA protein abundance are measured for each variant. 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The panel includes p.Gly555Glu, which scores at the low end of enzymatic activity, and the authors attribute its effect to disruption of SDHA-SDHB binding - a full-text derivation recorded in this entry's notes rather than a verified quotation, because the cached reference is abstract-only and names no individual variant.","url":"https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy_1GG.html#experimental-model-hap1-sdha-knockout-cell-line-with-single-variant-reintroduction","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ADilated_Cardiomyopathy_1GG:pathophysiology:Destabilised%20Flavoprotein-Iron-Sulfur%20Subunit%20Interface","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Destabilised Flavoprotein-Iron-Sulfur Subunit Interface","description":"The molecular consequence of the substitution, and the step at which the published biochemistry is most direct. In the proband studied by immunochemistry, the amount of flavoprotein and of the iron-containing subunit were both reduced, and the assembled 130 kDa holoenzyme was reduced further still. A loss of assembled complex that exceeds the loss of its individual subunits is the signature of an interaction that has become labile rather than of a subunit that is absent, which is the basis for placing residue 555 in the interacting domain.\nAn independent human cell system reaches the same conclusion by a different route. A clonal SDHA-knockout line into which SDHA missense variants are reintroduced singly, and in which succinate dehydrogenase activity is then measured directly, includes p.Gly555Glu in its panel; the variant scores at the low end of enzymatic activity and the authors attribute its effect to disruption of SDHA-SDHB binding. That per-variant result is a full-text derivation and is recorded as such in this entry's notes, not as a verified quotation.","url":"https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy_1GG.html#pathophysiology-destabilised-flavoprotein-iron-sulfur-subunit-interface","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ADilated_Cardiomyopathy_1GG:pathophysiology:Myocardium-Restricted%20Loss%20of%20Succinate%20Dehydrogenase%20Activity","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Myocardium-Restricted Loss of Succinate Dehydrogenase Activity","description":"The node that distinguishes this disease from every other SDHA phenotype, and the one nothing published explains. The same homozygous allele, present in every cell, produces a severe deficit of succinate dehydrogenase activity in cardiac muscle while substantial activity persists in skeletal muscle and in lymphoblastoid cells. The measured residual activities - roughly 15-21% of control in heart against 50-56% in skeletal muscle and 60-63% in lymphoblastoid cells - are a full-text derivation recorded in this entry's notes; the cached abstract states the pattern qualitatively.\nEvery explanation available for tissue-restricted respiratory-chain disease elsewhere is unavailable here. There is no heteroplasmy to invoke, because all four complex II subunits and both relevant assembly factors are nuclear-encoded and therefore present at the same dose in every tissue. The reporting authors sequenced SDHB, SDHD and SDHAF1 and found no modifier allele. What remains is a tissue-dependent difference in how much residual complex II a cell can tolerate, or in how efficiently the destabilised interface is assembled or degraded in cardiac mitochondria, and neither has been tested.","url":"https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy_1GG.html#pathophysiology-myocardium-restricted-loss-of-succinate-dehydrogenase-activity","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ADilated_Cardiomyopathy_1GG:pathophysiology:SDHA%20p.Gly555Glu%20Homozygosity","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"SDHA p.Gly555Glu Homozygosity","description":"Homozygosity for SDHA c.1664G>A, which substitutes a small uncharged glycine at position 555 of the flavoprotein subunit with glutamic acid. 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AAGGG tracts also stall replication in yeast plasmids and SV40-origin episomes in human cells, with orientation dependence. Lack of enhancement after PIF1 deletion favors a triplex contribution in yeast. These assays use short repeats or non-native replication systems; they do not establish replication-fork injury in postmitotic CANVAS neurons.","url":"https://dismech.monarchinitiative.org/pages/disorders/CANVAS.html#pathophysiology-repeat-associated-replication-fork-stalling","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ACANVAS:pathophysiology:Repeat%20DNA%20Secondary%20Structures","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Repeat DNA Secondary Structures","description":"Short synthetic AAGGG DNA repeats adopt G-quadruplex or H-r triplex structures under different ionic and temperature conditions. Triplex-sensitive probing and cellular replication assays argue against assigning all stalling to G-quadruplexes. 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Wild-type lines protect against all-trans-retinal toxicity; mutant lines do not, and instead show oxidative and ER stress with sXBP1, CHOP and ATF4 upregulated.\nIts limitation is structural rather than technical: HEK-293 cells are not photoreceptors, have no outer segment, no visual cycle and no light exposure, so the system can show that mutant RDH12 fails to protect a cell from all-trans-retinal, and cannot show that this is what kills a photoreceptor.","notes":null,"context_id":"disorder:Leber_Congenital_Amaurosis_13","context_kind":"Disorder","disease_name":"Leber Congenital Amaurosis 13","disease_synonyms":["LCA13","RDH12-associated retinal degeneration","RDH12 retinopathy","retinal dystrophy, early-onset severe, RDH12-related"],"disease_term":{"id":"MONDO:0012990","label":"Leber congenital amaurosis 13","display_label":"RDH12-associated retinal degeneration","url":"http://purl.obolibrary.org/obo/MONDO_0012990"},"experimental_model_type":"CELL_LINE","experimental_model_type_label":"Cell line","namo_type":"namo:CellLineModel","declared_namo_class_name":null,"namo_class_name":"CellLineModel","namo_class_label":"Cell Line Model","namo_description":"A model system based on immortalized cell lines that can be maintained in culture indefinitely. 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Fidelity is graded LOW for that reason despite the result being clean and internally controlled.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[{"id":"CL:0000210","label":"photoreceptor cell","display_label":"photoreceptor cell","url":"http://purl.obolibrary.org/obo/CL_0000210"}],"biological_processes":[{"id":"GO:0034976","label":"response to endoplasmic reticulum stress","display_label":"response to endoplasmic reticulum stress","url":"http://purl.obolibrary.org/obo/GO_0034976"},{"id":"GO:0006979","label":"response to oxidative stress","display_label":"response to oxidative stress","url":"http://purl.obolibrary.org/obo/GO_0006979"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"sXBP1, CHOP and ATF4 expression","description":null,"target":"Endoplasmic Reticulum and Oxidative Stress","direction":"INCREASED","interpretation":"Upregulation of three unfolded-protein-response effectors in mutant but not wild-type lines.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:34445569","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/34445569","reference_title":"Involvement of Oxidative and Endoplasmic Reticulum Stress in RDH12-Related Retinopathies.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"inducing oxidative and endoplasmic reticulum (ER) stress, with upregulation of sXBP1, CHOP, and ATF4","explanation":"The measurement behind this readout."}],"notes":null}],"evidence":[{"reference":"PMID:34445569","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/34445569","reference_title":"Involvement of Oxidative and Endoplasmic Reticulum Stress in RDH12-Related Retinopathies.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"HEK-293 cell lines expressing wildtype (WT) and mutant RDH12 were created. The WT cells afforded protection from atRAL-induced toxicity and oxidative stress.","explanation":"The system and its wild-type control."},{"reference":"PMID:34445569","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/34445569","reference_title":"Involvement of Oxidative and Endoplasmic Reticulum Stress in RDH12-Related Retinopathies.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"inducing oxidative and endoplasmic reticulum (ER) stress, with upregulation of sXBP1, CHOP, and ATF4","explanation":"The measurement behind this readout."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Leber_Congenital_Amaurosis_13","model_node_id":"model:kb/disorders/Leber_Congenital_Amaurosis_13.yaml:HEK-293 lines expressing wild-type and mutant RDH12","focus_node_id":"node:disorder%3ALeber_Congenital_Amaurosis_13:pathophysiology:Endoplasmic%20Reticulum%20and%20Oxidative%20Stress","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Leber_Congenital_Amaurosis_13.html#pathograph","nodes":[{"id":"model:kb/disorders/Leber_Congenital_Amaurosis_13.yaml:HEK-293 lines expressing wild-type and mutant RDH12","kind":"experimental_model","kind_label":"NAM model","label":"HEK-293 lines expressing wild-type and mutant RDH12","description":"A heterologous expression system, and the source of the entry's ER and oxidative stress node and of the pregabalin result. 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In HEK-293 lines expressing wild-type RDH12, the enzyme protects against all-trans-retinal toxicity and oxidative stress. Lines expressing mutant RDH12 have reduced protein expression and activity, cannot protect, and instead show oxidative and endoplasmic reticulum stress with upregulation of sXBP1, CHOP and ATF4 - the IRE1, ATF6 and PERK arms of the unfolded protein response respectively, and CHOP in particular is the pro-apoptotic output of that response.\nGraded PROVISIONAL: this is a heterologous expression system, not a photoreceptor, and the transcriptional response has not been demonstrated in an RDH12-deficient retina. It is curated as a distinct node rather than folded into the aldehyde toxicity above because it is the step pregabalin acts on, and because its addition is what stops the two-way question about which toxic species kills the cell from reading as a false binary - stress signalling is the shared downstream consequence either way.","url":"https://dismech.monarchinitiative.org/pages/disorders/Leber_Congenital_Amaurosis_13.html#pathophysiology-endoplasmic-reticulum-and-oxidative-stress","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ALeber_Congenital_Amaurosis_13:pathophysiology:Photoreceptor%20Degeneration","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Photoreceptor Degeneration","description":"Progressive loss of rod and cone photoreceptors. Functionally it is complete early: scotopic and photopic electroretinography was markedly reduced in every subject of the natural-history cohort, with a non-recordable ERG documented at one year of age.\nThe word to hold onto is *progressive*. The gene-discovery series described a severe yet progressive rod-cone dystrophy, and the natural-history data show reduced but often useful vision retained into adolescence before severe loss of function and structure after age ten. That trajectory is what makes treatment timing the central clinical question here.","url":"https://dismech.monarchinitiative.org/pages/disorders/Leber_Congenital_Amaurosis_13.html#pathophysiology-photoreceptor-degeneration","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ALeber_Congenital_Amaurosis_13:pathophysiology:Retinaldehyde%20and%20Aldehyde%20Toxicity%20in%20the%20Inner%20Segment","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Retinaldehyde and Aldehyde Toxicity in the Inner Segment","description":"Unreduced all-trans-retinal is a reactive aldehyde, and it accumulates in the compartment that holds the photoreceptor's mitochondria and endoplasmic reticulum. 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Extracellular 4-aminobenzoic acid restored currents at allele-dependent concentrations. Cryo-EM of purified BEST1-PABA complexes supports extracellular binding and neck-gate opening. The study did not demonstrate retinal rescue in patients.","notes":null,"context_id":"disorder:BEST1_Bestrophinopathies","context_kind":"Disorder","disease_name":"BEST1 Bestrophinopathies","disease_synonyms":[],"disease_term":{"id":null,"label":"BEST1 bestrophinopathy spectrum","display_label":"BEST1 bestrophinopathy spectrum","url":null},"experimental_model_type":"CELL_LINE","experimental_model_type_label":"Cell line","namo_type":"namo:CellLineModel","declared_namo_class_name":null,"namo_class_name":"CellLineModel","namo_class_label":"Cell Line Model","namo_description":"A model system based on immortalized cell lines that can be maintained in culture indefinitely. Examples: HepG2, A549, Caco-2, etc.","namo_docs_url":"https://monarch-initiative.github.io/namo/elements/CellLineModel/","namo_ontology_url":"https://w3id.org/monarch-initiative/namo/CellLineModel","namo_mapping_basis":"Safe mapping from DisMech category","namo_class_in_schema":true,"namo_schema_status":"Defined in NAMO schema used for this build","modality":"Cellular system","organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[{"id":"CL:0002586","label":"retinal pigment epithelial cell","display_label":"Retinal Pigment Epithelial Cell","url":"http://purl.obolibrary.org/obo/CL_0002586"}],"linked_cell_type_labels":["retinal pigment epithelial cell"],"cell_types":[{"id":"CL:0002586","label":"retinal pigment epithelial cell","display_label":"Retinal Pigment Epithelial Cell","url":"http://purl.obolibrary.org/obo/CL_0002586"}],"cell_type_labels":["retinal pigment epithelial cell"],"conditions":[],"cell_source":null,"source_category":"Immortalized / cell line","culture_system":null,"publication":"DOI:10.1038/s41467-024-54938-z","publication_url":null,"mechanisms":[{"target":"BEST1 Channel Dysfunction","target_url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathophysiology-best1-channel-dysfunction","relationship":"RESCUES","relationship_label":"Rescues","fidelity":"NOT_SPECIFIED","fidelity_label":"Not Specified","description":null,"limitations":"Selected loss-of-function constructs and an imposed coexpression ratio; gain-of-function variants and recessive mutants require separate assessment.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[{"id":"CL:0002586","label":"retinal pigment epithelial cell","display_label":"Retinal Pigment Epithelial Cell","url":"http://purl.obolibrary.org/obo/CL_0002586"}],"biological_processes":[{"id":"GO:0006821","label":"chloride transport","display_label":"Chloride Transport","url":"http://purl.obolibrary.org/obo/GO_0006821"}],"pathways":[],"genes":[{"id":"hgnc:12703","label":"BEST1","display_label":"BEST1","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/12703"}],"chemicals":[],"readouts":[],"evidence":[],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:BEST1_Bestrophinopathies","model_node_id":"model:kb/disorders/BEST1_Bestrophinopathies.yaml:HEK293 BEST1 mutant and wild-type coexpression with PABA rescue","focus_node_id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:BEST1%20Channel%20Dysfunction","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathograph","nodes":[{"id":"model:kb/disorders/BEST1_Bestrophinopathies.yaml:HEK293 BEST1 mutant and wild-type coexpression with PABA rescue","kind":"experimental_model","kind_label":"NAM model","label":"HEK293 BEST1 mutant and wild-type coexpression with PABA rescue","description":"Whole-cell patch clamp tested six mutant constructs (p.Ala10Thr, p.Arg218His, p.Leu234Pro, p.Ala243Thr, p.Gln293Lys and p.Asp302Ala) coexpressed with wild-type BEST1 at a 4:1 mutant:wild-type ratio. Extracellular 4-aminobenzoic acid restored currents at allele-dependent concentrations. Cryo-EM of purified BEST1-PABA complexes supports extracellular binding and neck-gate opening. The study did not demonstrate retinal rescue in patients.","url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#experimental-model-hek293-best1-mutant-and-wild-type-coexpression-with-paba-rescue","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:BEST1%20Channel%20Dysfunction","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"BEST1 Channel Dysfunction","description":"BEST1 encodes a pentameric calcium-activated anion channel of the RPE basolateral membrane. Variant effects differ: selected dominant patient-derived RPE lines have greatly reduced calcium-activated chloride currents, whereas p.Pro77Ser RPE shows increased halide permeability in a fluorescent biosensor assay. Reduced protein abundance, altered localization and channel-gating defects are allele-dependent. Dominant inheritance does not imply a uniform dominant-negative loss of channel activity.","url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathophysiology-best1-channel-dysfunction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:BEST1%20Deep-Intronic%20Splice%20Alteration","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"BEST1 Deep-Intronic Splice Alteration","description":"On NM_004183.4, c.1101-491A>G activates a cryptic donor and yields a 204-nucleotide pseudoexon. c.867+97G>A and c.867+97G>T increase use of an alternative intron-7 donor, producing a 203-nucleotide intron-retaining transcript. Both the canonical and longer transcripts occur in normal tissues; the variants shift their relative abundance. Minigene and patient PBMC RNA assays support splice alteration, while the predicted premature termination products and nonsense-mediated decay were not directly demonstrated at the protein or RNA-decay level. Patient RPE splice proportions remain uncertain.","url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathophysiology-best1-deep-intronic-splice-alteration","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:Delayed%20Photoreceptor%20Outer-Segment%20Protein%20Degradation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Delayed Photoreceptor Outer-Segment Protein Degradation","description":"Selected dominant BEST1 patient-derived iPSC-RPE models show delayed degradation of rhodopsin after photoreceptor outer-segment feeding. Wild-type BEST1 augmentation improved this endpoint in p.Arg218Cys and p.Asn296His cells but not p.Ala146Lys cells. This is a post-feeding protein-clearance readout and does not by itself measure outer-segment internalization or prove the composition of human vitelliform lesions.","url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathophysiology-delayed-photoreceptor-outer-segment-protein-degradation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:Impaired%20Photoreceptor%20Outer-Segment%20Internalization","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Photoreceptor Outer-Segment Internalization","description":"RPE differentiated from one ARB donor carrying p.Arg141His and p.Ile366fsTer18 internalized photoreceptor outer segments less efficiently than parental and unrelated control RPE. After three hours, two ARB clones internalized approximately 24% and 31% of associated outer segments versus approximately 42% in controls. This measures uptake, distinct from subsequent rhodopsin degradation. The causal contribution of reduced BEST1 abundance versus mutant-protein dysfunction was unresolved.","url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathophysiology-impaired-photoreceptor-outer-segment-internalization","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:Reduced%20BEST1%20Membrane%20Localization","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced BEST1 Membrane Localization","description":"Selected BEST1 mutants fail to accumulate normally at the membrane. This can reduce anion-channel activity, but other pathogenic alleles retain basolateral localization; preserved localization alone does not establish normal function.","url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathophysiology-reduced-best1-membrane-localization","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:Reduced%20RPE%20Transepithelial%20Fluid%20Transport","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced RPE Transepithelial Fluid Transport","description":"Patient-derived ARB iPSC-RPE monolayers showed reduced apical-to-basal fluid transport despite preserved epithelial morphology and no significant change in transepithelial electrical resistance. In a study of one ARB donor, one dominant Best disease donor and two controls, fluid flow was 0.12, 0.29 and 0.35 microliters/hour/cm2, respectively. This cellular transport defect provides a candidate explanation for fluid accumulation; the small donor sample does not establish its magnitude across BEST1 genotypes or demonstrate that epithelial barrier breakdown is required.","url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathophysiology-reduced-rpe-transepithelial-fluid-transport","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:Retinal%20Pigment%20Epithelium%20Atrophy","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Retinal Pigment Epithelium Atrophy","description":"Imaging can demonstrate loss of RPE at the macula and, in ARB, peripheral patches. Atrophy is distinct from persistent fluid and from fibrosis. The route from altered channel function and outer-segment handling to RPE cell loss remains incompletely resolved, and atrophy is not present at every disease stage.","url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathophysiology-retinal-pigment-epithelium-atrophy","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:RPE%20Apical%20Microvillar%20Underdevelopment","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"RPE Apical Microvillar Underdevelopment","description":"Recessive canine BEST1 disease shows fewer and shorter RPE apical microvilli before visible retinal lesions, with loss of cone outer-segment ensheathment and compromised interphotoreceptor matrix in established disease. These structural defects were absent in the comparator CNGB3 cone-channelopathy model. Altered calcium-dependent EZRIN activation is a proposed intermediate, not a directly tested BEST1-to-EZRIN pathway.","url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathophysiology-rpe-apical-microvillar-underdevelopment","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"}],"edges":[{"id":"model-link:0:model:kb/disorders/BEST1_Bestrophinopathies.yaml:HEK293 BEST1 mutant and wild-type coexpression with PABA rescue","source_id":"model:kb/disorders/BEST1_Bestrophinopathies.yaml:HEK293 BEST1 mutant and wild-type coexpression with PABA rescue","target_id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:BEST1%20Channel%20Dysfunction","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Rescues","directed":false,"relationship":"RESCUES","fidelity":"NOT_SPECIFIED","causal_link_type":null,"causal_link_type_label":null,"description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ABEST1_Bestrophinopathies:1:2","source_id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:BEST1%20Channel%20Dysfunction","target_id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:Delayed%20Photoreceptor%20Outer-Segment%20Protein%20Degradation","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[2]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"Augmentation restored channel activity and protein clearance in responsive lines, but did not isolate the causal coupling between these readouts.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ABEST1_Bestrophinopathies:1:3","source_id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:BEST1%20Channel%20Dysfunction","target_id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:Impaired%20Photoreceptor%20Outer-Segment%20Internalization","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[3]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"Anion/calcium signaling or insufficient protein could impair uptake in the ARB model; 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this does not demonstrate restoration of vision."}],"evidence_text":["we individually co-transfected six patient-derived dominant LOF mutants (A10T, R218H, L234P, A243T, Q293K and D302A) along with WT Best1 into HEK293 cells at a 4:1 ratio","and were fully rescued by PABA at different concentrations","The six clinical-origin mutant constructs were tested in engineered HEK293 cells with a chosen mutant:wild-type expression ratio, not in cells derived from these patients.","PABA restored the reduced whole-cell chloride currents in the six engineered coexpression conditions; this does not demonstrate restoration of vision."],"evidence_status":"Evidence recorded","metadata_completeness":60,"metadata_present":["Model category","NAMO class","Cell type","Modeled mechanism","Publication","Evidence"],"metadata_missing":["Organism","Anatomy","Cell source","Culture system"],"dataset_context":"Available in same entry","context_dataset_ids":["dataset:bioproject:prjna633668"],"candidate_dataset_ids":[],"source_path":"kb/disorders/BEST1_Bestrophinopathies.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/BEST1_Bestrophinopathies.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#experimental-model-hek293-best1-mutant-and-wild-type-coexpression-with-paba-rescue","source_anchor":"experimental-model-hek293-best1-mutant-and-wild-type-coexpression-with-paba-rescue"},{"id":"model:kb/disorders/CDK19-Related_Disorder.yaml:HEK293 CDK19 Autophosphorylation Assay","name":"HEK293 CDK19 Autophosphorylation Assay","description":"Immunoprecipitated kinase was assayed for autophosphorylation. 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That distinction is what makes pharmacochaperone rescue conceivable at all, and it is why a cell-permeable non-peptide ligand can restore membrane expression of a mutant receptor that a membrane-impermeant peptide agonist could never reach.","url":"https://dismech.monarchinitiative.org/pages/disorders/X-Linked_Nephrogenic_Diabetes_Insipidus.html#pathophysiology-endoplasmic-reticulum-retention-of-misfolded-v2-receptor","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AX-Linked_Nephrogenic_Diabetes_Insipidus:pathophysiology:AVPR2%20Loss-of-Function%20Variant","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"AVPR2 Loss-of-Function Variant","description":"A hemizygous pathogenic variant in AVPR2 on Xq28, the gene encoding the arginine vasopressin V2 receptor. The allelic spectrum is wide and largely private: 82 different putative disease-causing variants were found among 117 families, and haplotype analysis indicates that recurrences of the same variant in apparently unrelated families arose independently rather than from a shared founder. Roughly a fifth of isolated cases are de novo, arising during oogenesis in the mother.","url":"https://dismech.monarchinitiative.org/pages/disorders/X-Linked_Nephrogenic_Diabetes_Insipidus.html#pathophysiology-avpr2-loss-of-function-variant","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AX-Linked_Nephrogenic_Diabetes_Insipidus:pathophysiology:Loss%20of%20Vasopressin-Stimulated%20cAMP%20and%20PKA%20Signalling","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Loss of Vasopressin-Stimulated cAMP and PKA Signalling","description":"Vasopressin normally acts on the principal cell through a single linear cascade: V2 receptor occupancy activates the stimulatory G protein Gs, Gs activates adenylyl cyclase, cAMP rises, and cAMP activates protein kinase A. 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Note what is intact: the hormone, the G protein, the cyclase and PKA itself are all normal, which is the reason every experimental strategy for XNDI has aimed at re-entering the cascade below the receptor.","url":"https://dismech.monarchinitiative.org/pages/disorders/X-Linked_Nephrogenic_Diabetes_Insipidus.html#pathophysiology-loss-of-vasopressin-stimulated-camp-and-pka-signalling","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/X-Linked_Nephrogenic_Diabetes_Insipidus.yaml:HEK293 cells expressing the S127F V2 receptor mutant","source_id":"model:kb/disorders/X-Linked_Nephrogenic_Diabetes_Insipidus.yaml:HEK293 cells expressing the S127F V2 receptor mutant","target_id":"node:disorder%3AX-Linked_Nephrogenic_Diabetes_Insipidus:pathophysiology:Endoplasmic%20Reticulum%20Retention%20of%20Misfolded%20V2%20Receptor","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Rescues","directed":false,"relationship":"RESCUES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"Establishes the ER localization and the functional consequence for one patient variant, then partially reverses both with two chemically and pharmacologically different chaperones.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AX-Linked_Nephrogenic_Diabetes_Insipidus:0:1","source_id":"node:disorder%3AX-Linked_Nephrogenic_Diabetes_Insipidus:pathophysiology:AVPR2%20Loss-of-Function%20Variant","target_id":"node:disorder%3AX-Linked_Nephrogenic_Diabetes_Insipidus:pathophysiology:Endoplasmic%20Reticulum%20Retention%20of%20Misfolded%20V2%20Receptor","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[1]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"The commonest route, and the one with a therapeutic handle. 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direct copper transfer by COX6B1 remains unproven."},{"reference":"PMID:41419202","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41419202","reference_title":"The cytochrome c oxidase subunit COX6B1 is required for redox-sensitive early assembly and late stabilization of complex IV.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"These experiments showed the total loss of fully assembled monomeric cIV (IV), cIV dimer (IV2), as well as SC III2IV in 6B1KO.","explanation":"Complete absence of these native forms is a result of engineered knockout; patient missense alleles can retain holoenzyme."},{"reference":"PMID:41419202","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41419202","reference_title":"The cytochrome c oxidase subunit COX6B1 is required for redox-sensitive early assembly and late stabilization of complex IV.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Even though the AOX-expressing cells displayed robust rates of routine respiration, titration of the AOX inhibitor (salicylhydroxamic acid) completely abolished oxygen consumption, indicating that in intact cells, oxygen consumption was exclusively happening through AOX (Fig. S3, C and D).","explanation":"Respiratory bypass restores flux through AOX, not normal native complex IV respiration."},{"reference":"PMID:39184436","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39184436","reference_title":"Mitochondrial translation is the primary determinant of secondary mitochondrial complex I deficiencies.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Despite efficient inhibition of ISR in cIV- (4dKO, 6BKO) and cV- (βKO) lacking cells, documented by (i) a significant decrease of ATF4 and its targets to wt levels (Figures 5E and 5F) and (ii) decreased eIF4EBP1 levels (Figures 5G and 5H), the level of cI subunits was not increased (Figures 5E–5H and S5D–S5F).","explanation":"ISRIB and eIF4EBP1 silencing fail to restore complex I; ISR activation is not established as the mediator of secondary complex I loss."},{"reference":"PMID:41419202","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41419202","reference_title":"The cytochrome c oxidase subunit COX6B1 is required for redox-sensitive early assembly and late stabilization of complex IV.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"On the other hand, the expression of either a C-terminal or an N-terminal FLAG-tagged COX6B2 isoform failed to even marginally rescue either MT-CO2 levels (Figs. 1F, S1D) or mitochondrial respiration (Fig. 1G).","explanation":"Non-rescue applies to the tested HEK293 expression context and does not establish behavior in all tissues."},{"reference":"PMID:41419202","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41419202","reference_title":"The cytochrome c oxidase subunit COX6B1 is required for redox-sensitive early assembly and late stabilization of complex IV.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The abundance of both MT-CO1 and all the other tested cIV subunits in SC I III2IVsub was also substantially augmented after AOX expression compared with 6B1KO, whereas IV2 and III2IV SCs remained absent (Figs. 4, C and D, S3B).","explanation":"AOX permits partial assembly and an incomplete respirasome while mature dimer and III2IV remain absent."},{"reference":"PMID:41419202","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41419202","reference_title":"The cytochrome c oxidase subunit COX6B1 is required for redox-sensitive early assembly and late stabilization of complex IV.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Thus, the introduction of the R20C variant disrupted cIV native forms and respiration to a greater extent than R20H, similar to the observations in patient-derived fibroblasts (30, 31).","explanation":"Direct comparison of human allele-expression models shows a more severe Arg20Cys defect without establishing a population genotype–prognosis rule."}],"evidence_text":["Altogether, these results suggest a block in cIV assembly at the stage of MT-CO2 maturation and/or incorporation.","These experiments showed the total loss of fully assembled monomeric cIV (IV), cIV dimer (IV2), as well as SC III2IV in 6B1KO.","Even though the AOX-expressing cells displayed robust rates of routine respiration, titration of the AOX inhibitor (salicylhydroxamic acid) completely abolished oxygen consumption, indicating that in intact cells, oxygen consumption was exclusively happening through AOX (Fig. S3, C and D).","Despite efficient inhibition of ISR in cIV- (4dKO, 6BKO) and cV- (βKO) lacking cells, documented by (i) a significant decrease of ATF4 and its targets to wt levels (Figures 5E and 5F) and (ii) decreased eIF4EBP1 levels (Figures 5G and 5H), the level of cI subunits was not increased (Figures 5E–5H and S5D–S5F).","On the other hand, the expression of either a C-terminal or an N-terminal FLAG-tagged COX6B2 isoform failed to even marginally rescue either MT-CO2 levels (Figs. 1F, S1D) or mitochondrial respiration (Fig. 1G).","The abundance of both MT-CO1 and all the other tested cIV subunits in SC I III2IVsub was also substantially augmented after AOX expression compared with 6B1KO, whereas IV2 and III2IV SCs remained absent (Figs. 4, C and D, S3B).","Thus, the introduction of the R20C variant disrupted cIV native forms and respiration to a greater extent than R20H, similar to the observations in patient-derived fibroblasts (30, 31).","Knockout cells retain MT-CO1/COX4/COX5A intermediates but lose MT-CO2 and mature complex IV; 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The motif partially overlaps the HDAC4 nuclear localization signal (residues 244-279).","url":"https://dismech.monarchinitiative.org/pages/disorders/Neurodevelopmental_Disorder_with_Central_Hypotonia_and_Dysmorphic_Facies.html#pathophysiology-hdac4-14-3-3-binding-site-missense-variant","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ANeurodevelopmental_Disorder_with_Central_Hypotonia_and_Dysmorphic_Facies:pathophysiology:Increased%20Nuclear%20HDAC4%20Co-repressor%20Activity","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Increased Nuclear HDAC4 Co-repressor Activity","description":"Vertebrate HDAC4 is catalytically inactive as a histone deacetylase in its own right and acts predominantly as a signal-dependent transcriptional co-repressor. 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This is the mechanistic step that distinguishes NEDCHF from HDAC4 haploinsufficiency; it is inferred from the binding data plus the known biology rather than measured directly in patient neurons, so the node is marked provisional.","url":"https://dismech.monarchinitiative.org/pages/disorders/Neurodevelopmental_Disorder_with_Central_Hypotonia_and_Dysmorphic_Facies.html#pathophysiology-increased-nuclear-hdac4-co-repressor-activity","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"}],"edges":[{"id":"model-link:0:model:kb/disorders/Neurodevelopmental_Disorder_with_Central_Hypotonia_and_Dysmorphic_Facies.yaml:HEK293 HDAC4 / 14-3-3 beta co-immunoprecipitation assay","source_id":"model:kb/disorders/Neurodevelopmental_Disorder_with_Central_Hypotonia_and_Dysmorphic_Facies.yaml:HEK293 HDAC4 / 14-3-3 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A later study did not reproduce the same A20S deoxylipid result under its conditions.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[],"biological_processes":[],"pathways":[],"genes":[{"id":"hgnc:11277","label":"SPTLC1","display_label":"SPTLC1","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/11277"}],"chemicals":[],"readouts":[],"evidence":[{"reference":"PMID:34459874","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/34459874","reference_title":"Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The SPTLC1 enzyme complex activity was determined using a photometric assay measuring the release of free coenzyme A (coA) from the condensation reaction between palmitoyl-CoA and L-serine, L-alanine, and L-glycine.","explanation":"Assay identifies the measured chemistry; no direct neuronal outcome."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Amyotrophic_Lateral_Sclerosis_27_Juvenile","model_node_id":"model:kb/disorders/Amyotrophic_Lateral_Sclerosis_27_Juvenile.yaml:HEK293FT substrate preference and serine-response assays","focus_node_id":"node:disorder%3AAmyotrophic_Lateral_Sclerosis_27_Juvenile:pathophysiology:Pathogenic%20SPTLC1%20Variation","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Amyotrophic_Lateral_Sclerosis_27,_Juvenile.html#pathograph","nodes":[{"id":"model:kb/disorders/Amyotrophic_Lateral_Sclerosis_27_Juvenile.yaml:HEK293FT substrate preference and serine-response assays","kind":"experimental_model","kind_label":"NAM model","label":"HEK293FT substrate preference and serine-response assays","description":"Stable expression of A20S or C133W was tested with a CoA-release photometric assay and mitochondrial probe imaging. 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Y23F retained association in the 2022 study; C133W also showed reduced association without the same canonical-lipid feedback defect. Purified ALS-variant complexes in the 2023 study retained ORMDL. 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A mouse lacking 4.1G with 4.1N at 22% of normal has normal basal transmission and long-term potentiation at 3 weeks.","url":"https://dismech.monarchinitiative.org/pages/disorders/Intellectual_Disability,_Autosomal_Dominant_11.html#pathophysiology-impaired-glutamatergic-synapse-function-and-plasticity","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AIntellectual_Disability_Autosomal_Dominant_11:pathophysiology:Reduced%204.1N%20Binding%20to%20GluA1","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced 4.1N Binding to GluA1","description":"Protein 4.1N binds a membrane-proximal region of the GluA1 C-terminus through a consensus sequence in its own C-terminal domain, and associates with GluA1 at excitatory synapses. 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This overlaps this node's elastic-fiber-assembly arm (GO:0048251 DECREASED) and its net aortic-wall-weakening consequence, but the graft's dominant mechanism is defective ECM SYNTHESIS/maturation (reduced collagen-modifying enzyme activity) rather than the MMP-driven ECM DISASSEMBLY (GO:0022617 INCREASED) this node principally asserts, so the model is graded a partial recapitulation rather than a full one.","limitations":"Direction conflict: this node describes increased TGF-beta signaling driving MMP-mediated extracellular-matrix disassembly (GO:0022617 INCREASED), but PMID:38718134 evidences the opposite arm -- defective ECM synthesis, with reduced collagen-modifying enzyme activity (e.g. P4HA2, P3H1, PLOD1, LOX) and ECM-formation gene sets enriched in the corrected (not mutant) grafts, and lower TGF-beta signaling in mutant grafts than in corrected ones. Both readouts recorded below are DECREASED, not INCREASED, so they support this node's elastic-fiber-assembly (GO:0048251 DECREASED) arm and the general aortic-wall-weakening/medial-degeneration anchor (aortopathy_tgfbeta_dysregulation#Aortic Medial Degeneration and Wall Weakening) rather than the MMP-driven degradation arm the node otherwise centers on. The graft is also a bioengineered tissue-construct implant rather than a native aorta, and models a single TGFBR1 missense allele (A230T); generalization to other TGFBR1 kinase-domain variants is not established.","biological_scale":null,"anatomy":[{"id":"UBERON:0000947","label":"aorta","display_label":"Aorta","url":"http://purl.obolibrary.org/obo/UBERON_0000947"}],"cell_types":[{"id":"CL:0000359","label":"vascular associated smooth muscle cell","display_label":"vascular associated smooth muscle cell","url":"http://purl.obolibrary.org/obo/CL_0000359"}],"biological_processes":[{"id":"GO:0022617","label":"extracellular matrix disassembly","display_label":"Extracellular Matrix Disassembly","url":"http://purl.obolibrary.org/obo/GO_0022617"},{"id":"GO:0048251","label":"elastic fiber assembly","display_label":"Elastic Fiber Assembly","url":"http://purl.obolibrary.org/obo/GO_0048251"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Graft mechanical strength (burst pressure, 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Orphanet classifies aortic aneurysm as Very frequent (99-80%) in LDS.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Loeys-Dietz_Syndrome.html#phenotype-aortic-aneurysm","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALoeys-Dietz_Syndrome:phenotype:Aortic%20Dissection","kind":"phenotype","kind_label":"Phenotype","label":"Aortic Dissection","description":"Aortic dissection is a life-threatening complication occurring at smaller aortic diameters than in Marfan syndrome. 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Dissections have occurred at aortic dimensions of 3.9-4.0 cm, unlike the 5.0 cm threshold in Marfan syndrome.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Loeys-Dietz_Syndrome.html#phenotype-aortic-root-aneurysm","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALoeys-Dietz_Syndrome:phenotype:Arterial%20Dissection","kind":"phenotype","kind_label":"Phenotype","label":"Arterial Dissection","description":"Dissection can occur in arteries throughout the body, not just the aorta. Orphanet classifies arterial dissection as Very frequent (99-80%).\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Loeys-Dietz_Syndrome.html#phenotype-arterial-dissection","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALoeys-Dietz_Syndrome:phenotype:Arterial%20Tortuosity","kind":"phenotype","kind_label":"Phenotype","label":"Arterial Tortuosity","description":"Widespread arterial tortuosity, particularly of the head and neck vessels. A distinguishing feature from Marfan syndrome. Increased vertebral arterial tortuosity is a marker of adverse aortic outcome.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Loeys-Dietz_Syndrome.html#phenotype-arterial-tortuosity","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALoeys-Dietz_Syndrome:phenotype:Atypical%20Scarring%20of%20Skin","kind":"phenotype","kind_label":"Phenotype","label":"Atypical Scarring of Skin","description":"Abnormal scarring pattern reflecting connective tissue fragility.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Loeys-Dietz_Syndrome.html#phenotype-atypical-scarring-of-skin","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALoeys-Dietz_Syndrome:phenotype:Bruising%20Susceptibility","kind":"phenotype","kind_label":"Phenotype","label":"Bruising Susceptibility","description":"Easy bruising reflecting vascular and connective tissue fragility.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Loeys-Dietz_Syndrome.html#phenotype-bruising-susceptibility","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALoeys-Dietz_Syndrome:phenotype:Mitral%20Regurgitation","kind":"phenotype","kind_label":"Phenotype","label":"Mitral Regurgitation","description":"Mitral valve insufficiency, an occasional cardiac feature.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Loeys-Dietz_Syndrome.html#phenotype-mitral-regurgitation","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALoeys-Dietz_Syndrome:pathophysiology:Paradoxical%20TGF-beta%20Signaling","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Paradoxical TGF-beta Signaling","description":"The six LDS genes all sit in the TGF-beta pathway: the receptors TGFBR1 and TGFBR2 (Types 1-2), the ligands TGFB2 and TGFB3 (Types 4-5), and the intracellular effectors SMAD3 and SMAD2 (Types 3 and 6). Although most variants are predicted to reduce pathway function, aortic-wall tissue from patients with TGFBR1/2, SMAD3, TGFB2 and TGFB3 variants paradoxically shows increased canonical and noncanonical TGF-beta signaling, with up-regulated TGF-beta ligand expression. This results in excessive SMAD2/3 phosphorylation and activation of ERK and p38 MAPK downstream targets that promote extracellular matrix degradation. SMAD2 and SMAD3 therefore appear here in two roles: as the mutated gene in Types 6 and 3, and, as the wild-type protein, as the phosphorylated readout of the paradoxical signal. The cited sources do not establish the aortic-wall signaling state for SMAD2 variants specifically; SMAD2 is placed on this node as a pathway member, not on the strength of a measured paradox.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Loeys-Dietz_Syndrome.html#pathophysiology-paradoxical-tgf-beta-signaling","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALoeys-Dietz_Syndrome:phenotype:Patent%20Ductus%20Arteriosus","kind":"phenotype","kind_label":"Phenotype","label":"Patent Ductus Arteriosus","description":"Patent ductus arteriosus is a congenital cardiovascular feature. Orphanet classifies this as Very frequent (99-80%).\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Loeys-Dietz_Syndrome.html#phenotype-patent-ductus-arteriosus","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALoeys-Dietz_Syndrome:phenotype:Pregnancy-Related%20Vascular%20Complications","kind":"phenotype","kind_label":"Phenotype","label":"Pregnancy-Related Vascular Complications","description":"High incidence of pregnancy-related complications including aortic dissection. Among 222 women with 522 pregnancies in a systematic review, 4% experienced aortic dissection with 1% peripartum mortality.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Loeys-Dietz_Syndrome.html#phenotype-pregnancy-related-vascular-complications","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALoeys-Dietz_Syndrome:phenotype:Spontaneous%20Pneumothorax","kind":"phenotype","kind_label":"Phenotype","label":"Spontaneous Pneumothorax","description":"Spontaneous pneumothorax, an occasional pulmonary feature.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Loeys-Dietz_Syndrome.html#phenotype-spontaneous-pneumothorax","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALoeys-Dietz_Syndrome:phenotype:Striae%20Distensae","kind":"phenotype","kind_label":"Phenotype","label":"Striae Distensae","description":"Stretch marks (striae) reflecting connective tissue fragility.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Loeys-Dietz_Syndrome.html#phenotype-striae-distensae","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALoeys-Dietz_Syndrome:phenotype:Translucent%20Skin","kind":"phenotype","kind_label":"Phenotype","label":"Translucent Skin","description":"Thin, velvety, translucent skin with easy bruising and visible veins. Scars may be atrophic and wound healing delayed.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Loeys-Dietz_Syndrome.html#phenotype-translucent-skin","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALoeys-Dietz_Syndrome:phenotype:Uterine%20Rupture","kind":"phenotype","kind_label":"Phenotype","label":"Uterine Rupture","description":"Uterine rupture during pregnancy, reflecting connective tissue fragility of the uterine wall. Orphanet classifies this as Very frequent (99-80%).\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Loeys-Dietz_Syndrome.html#phenotype-uterine-rupture","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Loeys-Dietz_Syndrome.yaml:hiPSC-derived bioengineered vascular graft, TGFBR1 A230T (LDS Type 1)","source_id":"model:kb/disorders/Loeys-Dietz_Syndrome.yaml:hiPSC-derived bioengineered vascular graft, TGFBR1 A230T (LDS Type 1)","target_id":"node:disorder%3ALoeys-Dietz_Syndrome:pathophysiology:Extracellular%20Matrix%20Degradation","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Partially Recapitulates","directed":false,"relationship":"PARTIALLY_RECAPITULATES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"TGFBR1 A230T bioengineered vascular grafts show defective extracellular-matrix gene expression, decreased collagen hydroxylation, and impaired smooth-muscle-cell organization. This overlaps this node's elastic-fiber-assembly arm (GO:0048251 DECREASED) and its net aortic-wall-weakening consequence, but the graft's dominant mechanism is defective ECM SYNTHESIS/maturation (reduced collagen-modifying enzyme activity) rather than the MMP-driven ECM DISASSEMBLY (GO:0022617 INCREASED) this node principally asserts, so the model is graded a partial recapitulation rather than a full one.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ALoeys-Dietz_Syndrome:2:0","source_id":"node:disorder%3ALoeys-Dietz_Syndrome:pathophysiology:Extracellular%20Matrix%20Degradation","target_id":"node:disorder%3ALoeys-Dietz_Syndrome:phenotype:Aortic%20Aneurysm","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[0]","label":"Causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":null,"causal_link_type_label":null,"description":"Degradation of elastic fibers and collagen weakens the aortic media, promoting aneurysmal dilation.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ALoeys-Dietz_Syndrome:2:1","source_id":"node:disorder%3ALoeys-Dietz_Syndrome:pathophysiology:Extracellular%20Matrix%20Degradation","target_id":"node:disorder%3ALoeys-Dietz_Syndrome:phenotype:Aortic%20Dissection","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[1]","label":"Causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":null,"causal_link_type_label":null,"description":"Progressive medial weakening predisposes to dissection, characteristically at smaller aortic diameters than in Marfan 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oeys-Dietz_Syndrome:phenotype:Spontaneous%20Pneumothorax","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[9]","label":"Causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":null,"causal_link_type_label":null,"description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ALoeys-Dietz_Syndrome:2:11","source_id":"node:disorder%3ALoeys-Dietz_Syndrome:pathophysiology:Extracellular%20Matrix%20Degradation","target_id":"node:disorder%3ALoeys-Dietz_Syndrome:phenotype:Striae%20Distensae","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[11]","label":"Causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":null,"causal_link_type_label":null,"description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ALoeys-Dietz_Syndrome:2:10","source_id":"node:disorder%3ALoeys-Dietz_Syndrome:pathophysiology:Extracellular%20Matrix%20Degradation","target_id":"node:disorder%3ALoeys-Dietz_Syndrome:phenotype:Translucent%20Skin","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[10]","label":"Causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":null,"causal_link_type_label":null,"description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ALoeys-Dietz_Syndrome:2:7","source_id":"node:disorder%3ALoeys-Dietz_Syndrome:pathophysiology:Extracellular%20Matrix%20Degradation","target_id":"node:disorder%3ALoeys-Dietz_Syndrome:phenotype:Uterine%20Rupture","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[7]","label":"Causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":null,"causal_link_type_label":null,"description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ALoeys-Dietz_Syndrome:0:0","source_id":"node:disorder%3ALoeys-Dietz_Syndrome:pathophysiology:Paradoxical%20TGF-beta%20Signaling","target_id":"node:disorder%3ALoeys-Dietz_Syndrome:pathophysiology:Extracellular%20Matrix%20Degradation","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[0]","label":"Causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":null,"causal_link_type_label":null,"description":"Enhanced TGF-beta/SMAD signaling drives matrix metalloproteinase upregulation and degradation of the aortic wall extracellular matrix.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0}]}}],"mechanism_names":["Extracellular Matrix Degradation"],"relationships":["Partially Recapitulates"],"fidelities":["Moderate"],"biological_scales":[],"system_context_sources":["Linked mechanism anatomy","Linked mechanism cell type"],"modeled_system_labels":["aorta","vascular associated smooth muscle cell"],"biological_process_terms":[{"id":"GO:0022617","label":"extracellular matrix disassembly","display_label":"Extracellular Matrix Disassembly","url":"http://purl.obolibrary.org/obo/GO_0022617"},{"id":"GO:0048251","label":"elastic fiber assembly","display_label":"Elastic Fiber Assembly","url":"http://purl.obolibrary.org/obo/GO_0048251"}],"biological_processes":["extracellular matrix disassembly","elastic fiber assembly"],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":["Graft mechanical strength (burst pressure, suture retention)","Collagen hydroxylation and ECM gene expression"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:38718134","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38718134","reference_title":"Bioengineered vascular grafts with a pathogenic TGFBR1 variant model aneurysm formation in vivo and reveal underlying collagen defects.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"highlighted the role of reduced collagen modifying enzyme activity in human TAA formation","explanation":"States the study's overall conclusion that reduced collagen-modifying enzyme activity, downstream of the TGFBR1 A230T variant, drives human thoracic aortic aneurysm formation, supporting this hiPSC graft model as informative for the ECM-degradation node."},{"reference":"PMID:38718134","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38718134","reference_title":"Bioengineered vascular grafts with a pathogenic TGFBR1 variant model aneurysm formation in vivo and reveal underlying collagen defects.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The TGFBR1A230T variant led to impaired mechanical properties of BVGs, resulting in lower burst pressure and suture retention strength.","explanation":"Directly measures the weakened mechanical performance that results from the ECM defect this node models."},{"reference":"PMID:38718134","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38718134","reference_title":"Bioengineered vascular grafts with a pathogenic TGFBR1 variant model aneurysm formation in vivo and reveal underlying collagen defects.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Histological analysis and protein assays validated quantitative and qualitative ECM defects in PatientA230T/+ BVGs and patient tissue, including decreased collagen hydroxylation.","explanation":"Documents the specific ECM/collagen molecular defect underlying the mechanical weakening in this TGFBR1-genotype human model."}],"evidence_text":["highlighted the role of reduced collagen modifying enzyme activity in human TAA formation","The TGFBR1A230T variant led to impaired mechanical properties of BVGs, resulting in lower burst pressure and suture retention strength.","Histological analysis and protein assays validated quantitative and qualitative ECM defects in PatientA230T/+ BVGs and patient tissue, including decreased collagen hydroxylation.","States the study's overall conclusion that reduced collagen-modifying enzyme activity, downstream of the TGFBR1 A230T variant, drives human thoracic aortic aneurysm formation, supporting this hiPSC graft model as informative for the ECM-degradation node.","Directly measures the weakened mechanical performance that results from the ECM defect this node models.","Documents the specific ECM/collagen molecular defect underlying the mechanical weakening in this TGFBR1-genotype human model."],"evidence_status":"Evidence recorded","metadata_completeness":80,"metadata_present":["Model category","Anatomy","Cell type","Cell source","Culture system","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Organism"],"dataset_context":"None recorded in same 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the study did not find significance versus Ctrl2.","The superoxide result depends on the control comparison; one recessive patient was studied."],"evidence_status":"Evidence recorded","metadata_completeness":40,"metadata_present":["Model category","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Organism","Anatomy","Cell type","Cell source","Culture system"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Autosomal_Dominant_Charcot-Marie-Tooth_Disease_Type_2K.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autosomal_Dominant_Charcot-Marie-Tooth_Disease_Type_2K.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_dominant_Charcot-Marie-Tooth_disease_type_2K.html#experimental-model-homozygous-gdap1-ser194ter-patient-derived-motor-neurons","source_anchor":"experimental-model-homozygous-gdap1-ser194ter-patient-derived-motor-neurons"},{"id":"model:kb/disorders/TRAPPC12-Related_Encephalopathy.yaml:Homozygous Phe227Val affected-person fibroblast model","name":"Homozygous Phe227Val affected-person fibroblast model","description":"Primary skin fibroblasts from one affected individual homozygous for c.679T>G (p.Phe227Val) show absent or highly reduced mature TRAPPC12, mild Golgi disorganization, slight ER enlargement, and altered neutral-lipid vesicle distribution. 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integrity","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3AUlcerative_Colitis:5:1","source_id":"node:disorder%3AUlcerative_Colitis:pathophysiology:Pathobiont%20Expansion","target_id":"node:disorder%3AUlcerative_Colitis:pathophysiology:Epithelial%20Barrier%20Dysfunction","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[5].downstream[1]","label":"Causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":null,"causal_link_type_label":null,"description":"AIEC can invade epithelial cells and disrupt tight junctions","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0}]}}],"mechanism_names":["Epithelial Barrier Dysfunction"],"relationships":["Measures"],"fidelities":["Low"],"biological_scales":[],"system_context_sources":["Model-level tissue","Model-level cell type"],"modeled_system_labels":["colon","colon epithelial cell"],"biological_process_terms":[{"id":"GO:0090557","label":"establishment of endothelial intestinal barrier","display_label":"Epithelial Barrier Function","url":"http://purl.obolibrary.org/obo/GO_0090557"}],"biological_processes":["establishment of endothelial intestinal barrier"],"pathway_terms":[],"pathways":[],"gene_terms":[{"id":"hgnc:5024","label":"HNF4A","display_label":"HNF4A","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/5024"},{"id":"hgnc:1748","label":"CDH1","display_label":"CDH1","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/1748"}],"genes":["HNF4A","CDH1"],"chemical_terms":[],"chemicals":[],"readout_names":["Mucus volume expansion after prostaglandin E2 stimulation"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[{"statement":"The colon chip reproduces human colonic mucus bilayer structure, making it useful for mechanistic study of mucus-barrier defects relevant to UC","evidence":[{"reference":"PMID:31778828","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/31778828","reference_title":"Human Colon-on-a-Chip Enables Continuous In Vitro Analysis of Colon Mucus Layer Accumulation and Physiology.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The Colon Chip supports spontaneous goblet cell differentiation and accumulation of a mucus bilayer with impenetrable and penetrable layers, and a thickness similar to that observed in the human colon, while maintaining a subpopulation of proliferative epithelial cells.","explanation":"Supports physiologic mucus-barrier fidelity in a human colon microphysiological system relevant to UC barrier biology."},{"reference":"PMID:31778828","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/31778828","reference_title":"Human Colon-on-a-Chip Enables Continuous In Vitro Analysis of Colon Mucus Layer Accumulation and Physiology.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The Colon Chip may offer a new preclinical tool to analyze the role of mucus in human intestinal homeostasis as well as diseases, such as ulcerative colitis and cancer.","explanation":"Supports inclusion as a restrained UC-adjacent organ-on-chip bridge rather than a direct disease-specific UC model."}]},{"statement":"The chip captures inflammatory mediator effects on mucus hydration without requiring animal models","evidence":[{"reference":"PMID:31778828","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/31778828","reference_title":"Human Colon-on-a-Chip Enables Continuous In Vitro Analysis of Colon Mucus Layer Accumulation and Physiology.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Live imaging of the mucus layer formation on-chip showed that stimulation of the colonic epithelium with prostaglandin E2, which is increased during inflammation, causes rapid mucus volume expansion via an Na-K-Cl cotransporter 1 ion channel-dependent increase in its hydration state, but no increase in de novo mucus secretion.","explanation":"Connects the platform to inflammatory mediator responses relevant to mucosal inflammation and mucus-layer physiology in UC."}]}],"findings_text":["The colon chip reproduces human colonic mucus bilayer structure, making it useful for mechanistic study of mucus-barrier defects relevant to UC","The chip captures inflammatory mediator effects on mucus hydration without requiring animal models"],"evidence":[{"reference":"PMID:31778828","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/31778828","reference_title":"Human Colon-on-a-Chip Enables Continuous In Vitro Analysis of Colon Mucus Layer Accumulation and Physiology.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"A human colon-on-a-chip (Colon Chip) microfluidic device lined by primary patient-derived colonic epithelial cells was used to recapitulate mucus bilayer formation, and to visualize mucus accumulation in living cultures noninvasively.","explanation":"Supports this as a human colon organ-on-chip platform for studying mucus-barrier mechanisms relevant to UC."},{"reference":"PMID:31778828","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/31778828","reference_title":"Human Colon-on-a-Chip Enables Continuous In Vitro Analysis of Colon Mucus Layer Accumulation and Physiology.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The Colon Chip may offer a new preclinical tool to analyze the role of mucus in human intestinal homeostasis as well as diseases, such as ulcerative colitis and cancer.","explanation":"The entry's own hedge that this is a restrained UC-adjacent bridge, matching the LOW fidelity and MEASURES relationship recorded here."},{"reference":"PMID:31778828","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/31778828","reference_title":"Human Colon-on-a-Chip Enables Continuous In Vitro Analysis of Colon Mucus Layer Accumulation and Physiology.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Live imaging of the mucus layer formation on-chip showed that stimulation of the colonic epithelium with prostaglandin E2, which is increased during inflammation, causes rapid mucus volume expansion via an Na-K-Cl cotransporter 1 ion channel-dependent increase in its hydration state, but no increase in de novo mucus secretion.","explanation":"Directly reports the PGE2 hydration readout and its limits."},{"reference":"PMID:31778828","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/31778828","reference_title":"Human Colon-on-a-Chip Enables Continuous In Vitro Analysis of Colon Mucus Layer Accumulation and Physiology.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The Colon Chip supports spontaneous goblet cell differentiation and accumulation of a mucus bilayer with impenetrable and penetrable layers, and a thickness similar to that observed in the human colon, while maintaining a subpopulation of proliferative epithelial cells.","explanation":"Supports physiologic mucus-barrier fidelity in a human colon microphysiological system relevant to UC barrier biology."}],"evidence_text":["A human colon-on-a-chip (Colon Chip) microfluidic device lined by primary patient-derived colonic epithelial cells was used to recapitulate mucus bilayer formation, and to visualize mucus accumulation in living cultures noninvasively.","The Colon Chip may offer a new preclinical tool to analyze the role of mucus in human intestinal homeostasis as well as diseases, such as ulcerative colitis and cancer.","Live imaging of the mucus layer formation on-chip showed that stimulation of the colonic epithelium with prostaglandin E2, which is increased during inflammation, causes rapid mucus volume expansion via an Na-K-Cl cotransporter 1 ion channel-dependent increase in its hydration state, but no increase in de novo mucus secretion.","The Colon Chip supports spontaneous goblet cell differentiation and accumulation of a mucus bilayer with impenetrable and penetrable layers, and a thickness similar to that observed in the human colon, while maintaining a subpopulation of proliferative epithelial cells.","Supports this as a human colon organ-on-chip platform for studying mucus-barrier mechanisms relevant to UC.","The entry's own hedge that this is a restrained UC-adjacent bridge, matching the LOW fidelity and MEASURES relationship recorded here.","Directly reports the PGE2 hydration readout and its limits.","Supports physiologic mucus-barrier fidelity in a human colon microphysiological system relevant to UC barrier biology."],"evidence_status":"Evidence recorded","metadata_completeness":100,"metadata_present":["Model category","NAMO class","Organism","Anatomy","Cell type","Cell source","Culture system","Modeled mechanism","Publication","Evidence"],"metadata_missing":[],"dataset_context":"Available in same 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Cortical organoids are grown in a 3D-printed scaffold device under rocking flow, which lets primary blood monocytes be perfused in and infiltrate the tissue non-invasively. Monocytes isolated from aged and from young human donors are then run against otherwise identical organoids. Aged-donor monocytes infiltrate more, raise aging-associated marker expression including p16 within the organoid, secrete more proinflammatory cytokine, and increase MCP-3 chemokine and prostaglandin E2 signaling; neurons next to the infiltrating cells take on an apoptotic morphology. Because donor age is the only variable separating the arms and no pathogen is present, the system isolates the module's chain from stimulus to tissue outcome in entirely human material.","notes":"Typed CO_CULTURE rather than ORGAN_ON_CHIP deliberately, following the organoid-plus-immune-cell precedent in drug_induced_liver_injury. The platform is a device, so either value is defensible, but the enum is single-valued and what makes this model informative here is the aged-donor monocyte coculture, not the scaffold. The intestine-on-a-chip attached to gut_dysbiosis is typed ORGAN_ON_CHIP on the same reasoning inverted: there the oxygen-gradient device is the distinctive feature. The divergence between the two is intended.\nThe first non-animal model on this module, and the only one of its models that is entirely human. It complements the two naked mole-rat entries under animal_models rather than duplicating them: those carry an intervention arm for the chain as a whole in a whole organism, while this one runs the stimulus-to-consequence chain in human tissue with donor age as the only variable. It does not resolve the HUMAN_MODEL_MISMATCH discussion this module records, which is about the naked mole-rat hyaluronan adaptation, and conforming disorder entries do not inherit these links.\nTwo limits apply across every link. The coculture is short, so the model speaks to the initiation of the chain and not to its chronicity, which is the defining feature of inflammaging. The responding tissue is young by construction: the authors note their organoids derive from human embryonic stem cells with long telomeres and do not reflect the senescent phenotypes of an aged brain, so this system tests whether an aged immune compartment is sufficient to inflame young tissue, not how aged tissue and an aged immune system interact.","context_id":"module:inflammaging","context_kind":"Module","disease_name":"Inflammaging Module","disease_synonyms":[],"disease_term":null,"experimental_model_type":"CO_CULTURE","experimental_model_type_label":"Co-culture","namo_type":"namo:CoCulture","declared_namo_class_name":"CoCulture","namo_class_name":"CoCulture","namo_class_label":"Co Culture","namo_description":"Co-culture systems combining multiple cell types to mimic  microenvironments and cell-cell interactions.","namo_docs_url":"https://monarch-initiative.github.io/namo/elements/CoCulture/","namo_ontology_url":"https://w3id.org/monarch-initiative/namo/CoCulture","namo_mapping_basis":"Explicit in DisMech","namo_class_in_schema":true,"namo_schema_status":"Defined in NAMO schema used for this build","modality":"Cellular system","organism":{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},"organism_label":"Homo sapiens","model_tissue":[{"id":"UBERON:0000956","label":"cerebral cortex","display_label":"cerebral cortex","url":"http://purl.obolibrary.org/obo/UBERON_0000956"}],"model_tissue_labels":["cerebral cortex"],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[{"id":"UBERON:0000956","label":"cerebral cortex","display_label":"cerebral cortex","url":"http://purl.obolibrary.org/obo/UBERON_0000956"}],"anatomy_labels":["cerebral cortex"],"tissue_label":"cerebral cortex","model_cell_types":[{"id":"CL:0010012","label":"cerebral cortex neuron","display_label":"cortical neuron","url":"http://purl.obolibrary.org/obo/CL_0010012"},{"id":"CL:0000860","label":"classical monocyte","display_label":"primary classical blood monocyte","url":"http://purl.obolibrary.org/obo/CL_0000860"}],"model_cell_type_labels":["cerebral cortex neuron","classical monocyte"],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[{"id":"CL:0010012","label":"cerebral cortex neuron","display_label":"cortical neuron","url":"http://purl.obolibrary.org/obo/CL_0010012"},{"id":"CL:0000860","label":"classical monocyte","display_label":"primary classical blood monocyte","url":"http://purl.obolibrary.org/obo/CL_0000860"}],"cell_type_labels":["cerebral cortex neuron","classical monocyte"],"conditions":["Cortical organoid without monocytes (baseline)","Young-donor primary monocyte coculture (comparator)","Aged-donor primary monocyte coculture"],"cell_source":"Human cortical organoids differentiated from the WA01 human embryonic stem cell line, cocultured with classical monocytes isolated from the peripheral blood mononuclear cells of young and aged human donors, three donors per group. The abstract describes the donor groups as 20 to 30 years and over 60 years while the methods describe them as under 35 and over 65, so the exact stratification is stated inconsistently within the paper. The methods also list the THP-1 monocyte line, but it appears only in the cell-culture paragraph and underpins none of the reported comparisons, every one of which uses primary donor monocytes.","source_category":"Primary / biopsy-derived","culture_system":"Cortical organoids confined in a 3D-printed tubular scaffold device under rocking flow, permitting perfusion and non-invasive infiltration of primary monocytes into the organoid over a coculture of roughly one to three days","publication":"PMID:35908805","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35908805","mechanisms":[{"target":"Age-Associated Inflammatory Stimuli","target_url":"https://dismech.monarchinitiative.org/pages/modules/inflammaging.html#pathophysiology-age-associated-inflammatory-stimuli","relationship":"PARTIALLY_RECAPITULATES","relationship_label":"Partially Recapitulates","fidelity":"MODERATE","fidelity_label":"Moderate","description":"Immune-cell dysregulation is one of the stimulus classes this node enumerates, and here it is instantiated with monocytes taken from elderly humans rather than with a surrogate insult. 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Three donors per group is a small sample for a phenotype with known inter-individual variability, and the paper states the donor age thresholds inconsistently between its abstract and its methods.","biological_scale":null,"anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0006954","label":"inflammatory response","display_label":"Inflammatory Response","url":"http://purl.obolibrary.org/obo/GO_0006954"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Aged-monocyte infiltration and induction of aging-associated markers in the organoid","description":null,"target":"Age-Associated Inflammatory Stimuli","direction":"INCREASED","interpretation":"Measured against young-donor monocytes on identical organoids. Greater infiltration establishes that the aged cells engage the tissue, and the rise in aging-associated markers including p16 establishes that they change its state, which together is what qualifies them as a stimulus for this node rather than a bystander.","biological_processes":[{"id":"GO:0030595","label":"leukocyte chemotaxis","display_label":"leukocyte chemotaxis","url":"http://purl.obolibrary.org/obo/GO_0030595"},{"id":"GO:0090398","label":"cellular senescence","display_label":"cellular senescence","url":"http://purl.obolibrary.org/obo/GO_0090398"}],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:35908805","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/35908805","reference_title":"Understanding Immune-Driven Brain Aging by Human Brain Organoid Microphysiological Analysis Platform.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The authors find that the aged monocytes increase infiltration and promote the expression of aging-related markers (e.g., higher expression of p16) within the human cortical organoids, indicating that aged monocytes may drive brain aging.","explanation":"Reports both measurements this readout records, and their direction against the young-donor comparator."}],"notes":null}],"evidence":[{"reference":"PMID:35908805","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/35908805","reference_title":"Understanding Immune-Driven Brain Aging by Human Brain Organoid Microphysiological Analysis Platform.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"we discovered that monocytes isolated from aged individuals could exert a unique phenotype on young brain organoids.","explanation":"Establishes that the aged origin of the immune cells is what produces the phenotype, which is what makes them a stimulus for this node rather than inflammation in general."},{"reference":"PMID:35908805","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/35908805","reference_title":"Understanding Immune-Driven Brain Aging by Human Brain Organoid Microphysiological Analysis Platform.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The authors find that the aged monocytes increase infiltration and promote the expression of aging-related markers (e.g., higher expression of p16) within the human cortical organoids, indicating that aged monocytes may drive brain aging.","explanation":"Reports both measurements this readout records, and their direction against the young-donor comparator."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"module:inflammaging","model_node_id":"model:kb/modules/inflammaging.yaml:Human cortical organoid microphysiological platform with aged-donor monocyte coculture","focus_node_id":"node:module%3Ainflammaging:pathophysiology:Age-Associated%20Inflammatory%20Stimuli","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/modules/inflammaging.html#pathograph","nodes":[{"id":"model:kb/modules/inflammaging.yaml:Human cortical organoid microphysiological platform with aged-donor monocyte coculture","kind":"experimental_model","kind_label":"NAM model","label":"Human cortical organoid microphysiological platform with aged-donor monocyte coculture","description":"A human brain organoid microphysiological analysis platform used to ask whether an aged peripheral immune compartment is sufficient to drive an inflammatory, aging-associated state in young human neural tissue. 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Regardless of the dominant source, these converge to drive a persistent inflammatory response.","url":"https://dismech.monarchinitiative.org/pages/modules/inflammaging.html#module-pathophysiology-age-associated-inflammatory-stimuli","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:module%3Ainflammaging:pathophysiology:Chronic%20Low-Grade%20Sterile%20Inflammation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Chronic Low-Grade Sterile Inflammation","description":"The persistent stimuli establish a chronic, low-grade, sterile inflammatory state - elevated circulating inflammatory mediators without overt infection. This is the defining central effector of inflammaging and the conserved node that disease-specific inflammatory drivers converge upon.","url":"https://dismech.monarchinitiative.org/pages/modules/inflammaging.html#module-pathophysiology-chronic-low-grade-sterile-inflammation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/modules/inflammaging.yaml:Human cortical organoid microphysiological platform with aged-donor monocyte coculture","source_id":"model:kb/modules/inflammaging.yaml:Human cortical organoid microphysiological platform with aged-donor monocyte coculture","target_id":"node:module%3Ainflammaging:pathophysiology:Age-Associated%20Inflammatory%20Stimuli","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Partially Recapitulates","directed":false,"relationship":"PARTIALLY_RECAPITULATES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"Immune-cell dysregulation is one of the stimulus classes this node enumerates, and here it is instantiated with monocytes taken from elderly humans rather than with a surrogate insult. 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Those cells behave as an active stimulus and not merely a marker: they infiltrate the tissue more and raise aging-associated marker expression within it.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:module%3Ainflammaging:0:0","source_id":"node:module%3Ainflammaging:pathophysiology:Age-Associated%20Inflammatory%20Stimuli","target_id":"node:module%3Ainflammaging:pathophysiology:Chronic%20Low-Grade%20Sterile%20Inflammation","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[0]","label":"Causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":null,"causal_link_type_label":null,"description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0}]}},{"target":"Chronic Low-Grade Sterile Inflammation","target_url":"https://dismech.monarchinitiative.org/pages/modules/inflammaging.html#pathophysiology-chronic-low-grade-sterile-inflammation","relationship":"PARTIALLY_RECAPITULATES","relationship_label":"Partially Recapitulates","fidelity":"MODERATE","fidelity_label":"Moderate","description":"Aged-donor monocytes raise proinflammatory cytokine secretion, assayed as MCP-3, interleukin-1 beta and tumour necrosis factor alpha, in a system containing no pathogen. The sterility this node's name turns on is therefore a property of the experiment rather than an inference, and the elevation is referenced to young-donor cells in the same tissue, which is the comparison the human circulating-cytokine literature can only make across individuals.","limitations":"The coculture runs for roughly one to three days, so what is captured is an acute response, not the chronic persistence this node's definition rests on; nothing here shows the state is self-sustaining. Mediators are read in the organoid microenvironment rather than in circulation, so this is not the elevated-circulating-mediator measurement the node describes and it does not connect directly to the module's circulating IL-6, CRP or TNF biomarkers. 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No patient-derived dental cells have been reported.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[{"id":"CL:0000060","label":"odontoblast","display_label":"odontoblast","url":"http://purl.obolibrary.org/obo/CL_0000060"}],"biological_processes":[{"id":"GO:0071895","label":"odontoblast differentiation","display_label":"odontoblast differentiation","url":"http://purl.obolibrary.org/obo/GO_0071895"},{"id":"GO:0042476","label":"odontogenesis","display_label":"odontogenesis","url":"http://purl.obolibrary.org/obo/GO_0042476"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Polarized odontoblastic differentiation of human dental pulp stem cells","description":null,"target":"Impaired BMP-Driven Odontoblast Differentiation","direction":"INCREASED","interpretation":"Added SCUBE3 raises odontoblastic differentiation, so the disease direction is the loss of that drive.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:37189178","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/37189178","reference_title":"Epithelium-derived SCUBE3 promotes polarized odontoblastic differentiation of dental mesenchymal stem cells and pulp regeneration.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"In hDPSCs, exogenous SCUBE3 promoted cell proliferation and migration via TGF-β signalling and accelerated odontoblastic differentiation via BMP2 signalling.","explanation":"The measured differentiation response to SCUBE3, and the pathway it runs through."}],"notes":null}],"evidence":[{"reference":"PMID:37189178","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/37189178","reference_title":"Epithelium-derived SCUBE3 promotes polarized odontoblastic differentiation of dental mesenchymal stem cells and pulp regeneration.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Our results demonstrate that epithelium-derived SCUBE3 translocates to Mes via a paracrine pathway, accelerates proliferation, migration, and polarized odontoblastic differentiation of Mes, and promotes vascularized pulp regeneration.","explanation":"The study's own summary of what this system showed, which is what makes it informative for the odontoblast node."},{"reference":"PMID:37189178","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/37189178","reference_title":"Epithelium-derived SCUBE3 promotes polarized odontoblastic differentiation of dental mesenchymal stem cells and pulp regeneration.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"In hDPSCs, exogenous SCUBE3 promoted cell proliferation and migration via TGF-β signalling and accelerated odontoblastic differentiation via BMP2 signalling.","explanation":"The measured differentiation response to SCUBE3, and the pathway it runs through."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:SCUBE3-Related_Short_Stature_Syndrome","model_node_id":"model:kb/disorders/SCUBE3-Related_Short_Stature_Syndrome.yaml:Human dental pulp stem cell and pulp-dentin organoid odontoblast model","focus_node_id":"node:disorder%3ASCUBE3-Related_Short_Stature_Syndrome:pathophysiology:Impaired%20BMP-Driven%20Odontoblast%20Differentiation","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/SCUBE3-Related_Short_Stature_Syndrome.html#pathograph","nodes":[{"id":"model:kb/disorders/SCUBE3-Related_Short_Stature_Syndrome.yaml:Human dental pulp stem cell and pulp-dentin organoid odontoblast model","kind":"experimental_model","kind_label":"NAM model","label":"Human dental pulp stem cell and pulp-dentin organoid odontoblast model","description":"A human organoid system for the dental arm of the mechanism. It supplies the step the disease is missing rather than removing it, so the inference is a sufficiency argument read in reverse.","url":"https://dismech.monarchinitiative.org/pages/disorders/SCUBE3-Related_Short_Stature_Syndrome.html#experimental-model-human-dental-pulp-stem-cell-and-pulp-dentin-organoid-odontoblast-model","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ASCUBE3-Related_Short_Stature_Syndrome:pathophysiology:Impaired%20BMP-Driven%20Odontoblast%20Differentiation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired BMP-Driven Odontoblast Differentiation","description":"The dental arm of the mechanism, which is separable from the bone arm rather than a restatement of it. Scube3 transcript in the developing tooth is epithelial, and the protein moves to the mesenchyme, so the defect is in an epithelial-to-mesenchymal instruction: without it, dental mesenchymal cells fail to differentiate into polarized odontoblasts. The epithelial side is affected too - Scube3 knockout ameloblasts are shorter and wider and lose their Tomes processes; ameloblasts are epithelial rather than the mesenchyme-derived odontoblasts this node is bound to, and are recorded here because ameloblast induction is a prerequisite for odontoblast differentiation. This is why dental anomalies are prominent enough to appear in the disorder's ISDS row rather than being an incidental finding.\n\nOne caveat on how much this node claims. Nothing has been measured in SCUBE3-deficient human or mouse teeth at the odontoblast level: the Scube3 knockout reports dental defects clinically, and the odontoblast step is a sufficiency result in healthy cells read in reverse. The DECREASED modifiers on the two GO processes are therefore an inference from the direction of those experiments rather than a measured reduction.","url":"https://dismech.monarchinitiative.org/pages/disorders/SCUBE3-Related_Short_Stature_Syndrome.html#pathophysiology-impaired-bmp-driven-odontoblast-differentiation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ASCUBE3-Related_Short_Stature_Syndrome:phenotype:Dental%20anomalies","kind":"phenotype","kind_label":"Phenotype","label":"Dental anomalies","description":"Prominent enough to be named in the disorder's ISDS row, and reproduced in the Scube3 knockout mouse - unusual among the group-21 disorders, most of which have no dental component.","url":"https://dismech.monarchinitiative.org/pages/disorders/SCUBE3-Related_Short_Stature_Syndrome.html#phenotype-dental-anomalies","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ASCUBE3-Related_Short_Stature_Syndrome:pathophysiology:Loss%20of%20SCUBE3%20BMP%20Co-Receptor%20Function","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Loss of SCUBE3 BMP Co-Receptor Function","description":"Biallelic inactivating SCUBE3 variants remove a membrane-associated BMP2/4 co-receptor. Wild-type SCUBE3 attracts BMP receptor complexes to lipid-raft microdomains and enhances BMP signalling, apparently by facilitating the interaction of BMP ligands with BMP type I receptors. The best-characterized illustration of what that loss costs at the protein level is the N294K substitution, which reaches the cell surface normally but fails to complex with BMP type IA receptor - so the defect is in receptor engagement, not in protein trafficking. Read that as mechanism rather than as a patient variant: N294K is a mouse ENU-induced allele and is not among the human variants this entry curates. It is informative here because it sits in the cbEGF7 calcium-binding repeat, the same module the human missense alleles disrupt.","url":"https://dismech.monarchinitiative.org/pages/disorders/SCUBE3-Related_Short_Stature_Syndrome.html#pathophysiology-loss-of-scube3-bmp-co-receptor-function","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/SCUBE3-Related_Short_Stature_Syndrome.yaml:Human dental pulp stem cell and pulp-dentin organoid odontoblast model","source_id":"model:kb/disorders/SCUBE3-Related_Short_Stature_Syndrome.yaml:Human dental pulp stem cell and pulp-dentin organoid odontoblast model","target_id":"node:disorder%3ASCUBE3-Related_Short_Stature_Syndrome:pathophysiology:Impaired%20BMP-Driven%20Odontoblast%20Differentiation","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Perturbs","directed":false,"relationship":"PERTURBS","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"Exogenous SCUBE3 accelerates polarized odontoblastic differentiation of human dental mesenchymal cells through BMP2 signalling.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ASCUBE3-Related_Short_Stature_Syndrome:2:0","source_id":"node:disorder%3ASCUBE3-Related_Short_Stature_Syndrome:pathophysiology:Impaired%20BMP-Driven%20Odontoblast%20Differentiation","target_id":"node:disorder%3ASCUBE3-Related_Short_Stature_Syndrome:phenotype:Dental%20anomalies","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Failure of polarized odontoblast differentiation is the cellular event behind the clinical dental findings.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":2},{"id":"causal:disorder%3ASCUBE3-Related_Short_Stature_Syndrome:0:1","source_id":"node:disorder%3ASCUBE3-Related_Short_Stature_Syndrome:pathophysiology:Loss%20of%20SCUBE3%20BMP%20Co-Receptor%20Function","target_id":"node:disorder%3ASCUBE3-Related_Short_Stature_Syndrome:pathophysiology:Impaired%20BMP-Driven%20Odontoblast%20Differentiation","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[1]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"The dental arm of the same co-receptor loss. 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Wnt activation rescued that differentiation readout. 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Androgens stimulate growth at other body sites, so signaling consequences depend on follicular context.","url":"https://dismech.monarchinitiative.org/pages/disorders/Androgenetic_Alopecia.html#pathophysiology-dihydrotestosterone-androgen-receptor-signaling","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAndrogenetic_Alopecia:pathophysiology:Impaired%20Follicular%20Epithelial%20Differentiation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Follicular Epithelial Differentiation","description":"Androgen-treated dermal papilla cells had reduced ability to induce hair keratin expression in cocultured follicular stem-cell preparations, restored by Wnt activation. 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Yeast experiments on neurological or zebrafish ortholog substitutions do not fill this gap.","url":"https://dismech.monarchinitiative.org/pages/disorders/46,XY_Sex_Reversal_11.html#pathophysiology-impaired-small-ribosomal-subunit-biogenesis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"HYPOTHETICAL","mechanism_confidence_label":"Hypothetical"},{"id":"node:disorder%3A46_XY_Sex_Reversal_11:pathophysiology:DHX37%20Missense%20Variation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"DHX37 Missense Variation","description":"Specific germline missense variants in DHX37 cause the testicular-development spectrum. Many cluster in the RecA-like helicase domains. Their shared biochemical effect is unresolved: domain location and enrichment establish a genetic association without proving decreased ATPase activity, dominant-negative action, gain of function or haploinsufficiency. Reports of variants of uncertain significance require separate interpretation.","url":"https://dismech.monarchinitiative.org/pages/disorders/46,XY_Sex_Reversal_11.html#pathophysiology-dhx37-missense-variation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3A46_XY_Sex_Reversal_11:pathophysiology:Nucleolar%20Structural%20Disruption","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Nucleolar Structural Disruption","description":"Sertoli-cell Dhx37 knockout mice show fragmented, smaller nucleoli by electron microscopy and reduced fibrillarin staining in adult testes. This supports nucleolar disruption following substantial experimental loss of Dhx37. The corresponding change in heterozygous human DSD remains provisional.","url":"https://dismech.monarchinitiative.org/pages/disorders/46,XY_Sex_Reversal_11.html#pathophysiology-nucleolar-structural-disruption","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"}],"edges":[{"id":"model-link:0:model:kb/disorders/46_XY_Sex_Reversal_11.yaml:Human DHX37 depletion and catalytic-mutant complementation","source_id":"model:kb/disorders/46_XY_Sex_Reversal_11.yaml:Human DHX37 depletion and catalytic-mutant complementation","target_id":"node:disorder%3A46_XY_Sex_Reversal_11:pathophysiology:Impaired%20Small%20Ribosomal%20Subunit%20Biogenesis","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Perturbs","directed":false,"relationship":"PERTURBS","fidelity":"LOW","causal_link_type":null,"causal_link_type_label":null,"description":"Depletion and catalytic perturbation impair small-subunit maturation; complementation with wild-type DHX37 reverses the processing defect.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":2},{"id":"causal:disorder%3A46_XY_Sex_Reversal_11:0:1","source_id":"node:disorder%3A46_XY_Sex_Reversal_11:pathophysiology:DHX37%20Missense%20Variation","target_id":"node:disorder%3A46_XY_Sex_Reversal_11:pathophysiology:Impaired%20Small%20Ribosomal%20Subunit%20Biogenesis","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[1]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"A proposed consequence of altered DHX37 function; direct DSD-allele ribosome-output measurements remain unavailable.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":2},{"id":"causal:disorder%3A46_XY_Sex_Reversal_11:2:0","source_id":"node:disorder%3A46_XY_Sex_Reversal_11:pathophysiology:Impaired%20Small%20Ribosomal%20Subunit%20Biogenesis","target_id":"node:disorder%3A46_XY_Sex_Reversal_11:pathophysiology:Nucleolar%20Structural%20Disruption","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[0]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"Ribosome-assembly defects are a proposed contributor to the nucleolar phenotype after mouse Dhx37 deletion; this intermediate has not been isolated experimentally.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1}]}}],"mechanism_names":["Impaired Small Ribosomal Subunit Biogenesis"],"relationships":["Perturbs"],"fidelities":["Low"],"biological_scales":["Molecular"],"system_context_sources":["Linked mechanism biological scale"],"modeled_system_labels":["Molecular"],"biological_process_terms":[{"id":"GO:0042274","label":"ribosomal small subunit biogenesis","display_label":"ribosomal small subunit biogenesis","url":"http://purl.obolibrary.org/obo/GO_0042274"}],"biological_processes":["ribosomal small subunit biogenesis"],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":["40S ribosomal subunit abundance","21S-to-18SE pre-rRNA processing","U3 snoRNA retention on pre-ribosomal complexes"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:30582406","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30582406","reference_title":"The human RNA helicase DHX37 is required for release of the U3 snoRNP from pre-ribosomal particles.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"depletion of DHX37 caused accumulation of the 21S pre-rRNA and a concomitant decrease in the levels of the 18SE pre-rRNA","explanation":"Northern blots establish a pre-rRNA processing defect after experimental DHX37 depletion in human cells."},{"reference":"PMID:30582406","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30582406","reference_title":"The human RNA helicase DHX37 is required for release of the U3 snoRNP from pre-ribosomal particles.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"expression of wild-type DHX37 from a transgene can rescue these defects","explanation":"HEK293 complementation rescues pre-rRNA processing after endogenous DHX37 depletion; engineered T282A fails to rescue the 21S-to-18SE defect. This is not rescue of a patient variant or gonadal phenotype."},{"reference":"PMID:30582406","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30582406","reference_title":"The human RNA helicase DHX37 is required for release of the U3 snoRNP from pre-ribosomal particles.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"depletion of DHX37 does not affect production of 60S subunits but leads to a significant decrease in the abundance of 40S particles as well as a decrease in the amount of 80S monosomes","explanation":"Sucrose-gradient analysis of DHX37-depleted human cultured cells directly measures reduced small-subunit abundance; the experiments do not test a human DSD allele."},{"reference":"PMID:30582406","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30582406","reference_title":"The human RNA helicase DHX37 is required for release of the U3 snoRNP from pre-ribosomal particles.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Expression of DHX37T282A lead to a notable increase in the proportion of the U3 snoRNA associated with pre-ribosomal complexes","explanation":"Fractionation and northern blotting show U3 retention with engineered catalytic T282A after endogenous DHX37 depletion, rather than a direct purified U3-duplex unwinding assay."}],"evidence_text":["depletion of DHX37 caused accumulation of the 21S pre-rRNA and a concomitant decrease in the levels of the 18SE pre-rRNA","expression of wild-type DHX37 from a transgene can rescue these defects","depletion of DHX37 does not affect production of 60S subunits but leads to a significant decrease in the abundance of 40S particles as well as a decrease in the amount of 80S monosomes","Expression of DHX37T282A lead to a notable increase in the proportion of the U3 snoRNA associated with pre-ribosomal complexes","Northern blots establish a pre-rRNA processing defect after experimental DHX37 depletion in human cells.","HEK293 complementation rescues pre-rRNA processing after endogenous DHX37 depletion; engineered T282A fails to rescue the 21S-to-18SE defect. This is not rescue of a patient variant or gonadal phenotype.","Sucrose-gradient analysis of DHX37-depleted human cultured cells directly measures reduced small-subunit abundance; the experiments do not test a human DSD allele.","Fractionation and northern blotting show U3 retention with engineered catalytic T282A after endogenous DHX37 depletion, rather than a direct purified U3-duplex unwinding assay."],"evidence_status":"Evidence recorded","metadata_completeness":60,"metadata_present":["Model category","NAMO class","Organism","Modeled mechanism","Publication","Evidence"],"metadata_missing":["Anatomy","Cell type","Cell source","Culture system"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/46_XY_Sex_Reversal_11.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/46_XY_Sex_Reversal_11.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/46,XY_Sex_Reversal_11.html#experimental-model-human-dhx37-depletion-and-catalytic-mutant-complementation","source_anchor":"experimental-model-human-dhx37-depletion-and-catalytic-mutant-complementation"},{"id":"model:kb/disorders/Ewing_Sarcoma.yaml:Human embryonic mesenchymal stem cell EWS-FLI1 transformation model","name":"Human embryonic mesenchymal stem cell EWS-FLI1 transformation model","description":"Early human embryonic mesenchymal stem cells transduced with EWS-FLI1 acquire an Ewing-like transcriptome. Tumor formation was tested separately in immunodeficient xenograft hosts. This engineered permissiveness differs from later MSC states tested in the study; it does not uniquely identify the human lineage of origin.","notes":null,"context_id":"disorder:Ewing_Sarcoma","context_kind":"Disorder","disease_name":"Ewing Sarcoma","disease_synonyms":[],"disease_term":{"id":"MONDO:0012817","label":"Ewing sarcoma","display_label":"Ewing sarcoma","url":"http://purl.obolibrary.org/obo/MONDO_0012817"},"experimental_model_type":"PRIMARY_CELL_CULTURE","experimental_model_type_label":"Primary-cell culture","namo_type":"namo:TwoDCellCulture","declared_namo_class_name":"TwoDCellCulture","namo_class_name":"TwoDCellCulture","namo_class_label":"2D Cell Culture","namo_description":"Conventional monolayer cell cultures grown on flat surfaces. Simple but limited in physiological relevance.","namo_docs_url":"https://monarch-initiative.github.io/namo/elements/TwoDCellCulture/","namo_ontology_url":"https://w3id.org/monarch-initiative/namo/TwoDCellCulture","namo_mapping_basis":"Explicit in DisMech","namo_class_in_schema":true,"namo_schema_status":"Defined in NAMO schema used for this build","modality":"Cellular system","organism":{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},"organism_label":"Homo sapiens","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[{"id":"CL:0000134","label":"mesenchymal stem cell","display_label":"mesenchymal stem cell","url":"http://purl.obolibrary.org/obo/CL_0000134"}],"model_cell_type_labels":["mesenchymal stem cell"],"linked_cell_types":[{"id":"CL:0000134","label":"mesenchymal stem cell","display_label":"early mesenchymal stem cell","url":"http://purl.obolibrary.org/obo/CL_0000134"},{"id":"CL:0000333","label":"migratory neural crest cell","display_label":"migratory neural crest cell","url":"http://purl.obolibrary.org/obo/CL_0000333"}],"linked_cell_type_labels":["mesenchymal stem cell","migratory neural crest cell"],"cell_types":[{"id":"CL:0000134","label":"mesenchymal stem cell","display_label":"mesenchymal stem cell","url":"http://purl.obolibrary.org/obo/CL_0000134"},{"id":"CL:0000333","label":"migratory neural crest cell","display_label":"migratory neural crest cell","url":"http://purl.obolibrary.org/obo/CL_0000333"}],"cell_type_labels":["mesenchymal stem cell","migratory neural crest cell"],"conditions":["Ewing sarcoma","EWS-FLI1 transformation","embryonic developmental context"],"cell_source":"Human embryonic mesenchymal stem cells (heMSCs) transduced with EWS::FLI1 lentivirus","source_category":"Primary / biopsy-derived","culture_system":"Primary embryonic MSC culture with lentiviral oncogene transduction and xenograft validation","publication":"PMID:41136396","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41136396","mechanisms":[{"target":"EWS-FLI1 Fusion Oncogene","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-ews-fli1-fusion-oncogene","relationship":"NOT_SPECIFIED","relationship_label":"Not Specified","fidelity":"NOT_SPECIFIED","fidelity_label":"Not Specified","description":"Models EWS-FLI1 oncogene expression in an embryonic human mesenchymal developmental context, with xenograft tumor formation demonstrating transformation capacity.","limitations":null,"biological_scale":null,"anatomy":[],"cell_types":[{"id":"CL:0000134","label":"mesenchymal stem cell","display_label":"early mesenchymal stem cell","url":"http://purl.obolibrary.org/obo/CL_0000134"},{"id":"CL:0000333","label":"migratory neural crest cell","display_label":"migratory neural crest cell","url":"http://purl.obolibrary.org/obo/CL_0000333"}],"biological_processes":[{"id":"GO:0045944","label":"positive regulation of transcription by RNA polymerase II","display_label":"positive regulation of transcription by RNA polymerase II","url":"http://purl.obolibrary.org/obo/GO_0045944"}],"pathways":[],"genes":[{"id":"hgnc:3508","label":"EWSR1","display_label":"EWSR1","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/3508"},{"id":"hgnc:3749","label":"FLI1","display_label":"FLI1","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/3749"}],"chemicals":[],"readouts":[],"evidence":[],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Ewing_Sarcoma","model_node_id":"model:kb/disorders/Ewing_Sarcoma.yaml:Human embryonic mesenchymal stem cell EWS-FLI1 transformation model","focus_node_id":"node:disorder%3AEwing_Sarcoma:pathophysiology:EWS-FLI1%20Fusion%20Oncogene","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathograph","nodes":[{"id":"model:kb/disorders/Ewing_Sarcoma.yaml:Human embryonic mesenchymal stem cell EWS-FLI1 transformation model","kind":"experimental_model","kind_label":"NAM model","label":"Human embryonic mesenchymal stem cell EWS-FLI1 transformation model","description":"Early human embryonic mesenchymal stem cells transduced with EWS-FLI1 acquire an Ewing-like transcriptome. Tumor formation was tested separately in immunodeficient xenograft hosts. This engineered permissiveness differs from later MSC states tested in the study; it does not uniquely identify the human lineage of origin.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#experimental-model-human-embryonic-mesenchymal-stem-cell-ews-fli1-transformation-model","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:EWS-FLI1%20Fusion%20Oncogene","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"EWS-FLI1 Fusion Oncogene","description":"The t(11;22)(q24;q12) translocation fuses the EWS gene (EWSR1) on chromosome 22 with the FLI1 gene on chromosome 11. The resulting EWS-FLI1 protein functions as an aberrant FET-ETS transcription factor. It is the truncal driver of most Ewing sarcomas, but its oncogenic effect depends on a permissive developmental cell state and on downstream enhancer, transcriptional, metabolic, and DNA damage-response programs.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-ews-fli1-fusion-oncogene","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:ATF4-Serine-Glycine%20Metabolic%20Reprogramming","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"ATF4-Serine-Glycine Metabolic Reprogramming","description":"EWS-FLI1 and menin converge on ATF4 to activate a serine synthesis pathway transcriptional program. EWS-FLI1 also upregulates glutamine uptake and one-carbon cycle genes, linking fusion-driven transcription to biosynthetic metabolism, redox state, and survival.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-atf4-serine-glycine-metabolic-reprogramming","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:BAF%20Complex%20Retargeting","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"BAF Complex Retargeting","description":"EWS-FLI1 uses the EWSR1 low-complexity/prion-like domain to retarget BRG1/BRM-associated factor (BAF/SWI-SNF) chromatin-remodeling complexes to tumor-specific enhancers. This neomorphic recruitment depends on tyrosine residues linked to phase-transition behavior of the EWSR1 domain and helps establish oncogenic enhancer activity.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-baf-complex-retargeting","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:DHX9%20Sequestration%20During%20Topoisomerase%20Stress","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"DHX9 Sequestration During Topoisomerase Stress","description":"Following topoisomerase I poison exposure, EWS-FLI1 sequesters DHX9 helicase and prevents resolution of drug-induced R-loops. Excess DHX9 or reduced fusion expression confers SN-38 resistance independent of measured proliferation and global transcription rates. This supports a protein-interaction contribution under topoisomerase stress, without proving complete independence from transcription or untreated tumor initiation.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-dhx9-sequestration-during-topoisomerase-stress","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:EWS-FLI1%20Chromatin%20Hub%20Dynamics","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"EWS-FLI1 Chromatin Hub Dynamics","description":"EWS-FLI1 low-complexity-domain interactions support GGAA-associated transcription within a narrow interaction-strength optimum. A 2026 bioRxiv preprint reports endogenous dynamic sub-diffraction hubs that dissolve before macroscopic liquid-liquid phase separation. This is a provisional refinement of the published interaction-optimum model, not evidence that macroscopic condensates are required for oncogenesis.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-ews-fli1-chromatin-hub-dynamics","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:EWS-FLI1%20Dosage%20and%20State%20Plasticity","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"EWS-FLI1 Dosage and State Plasticity","description":"Fusion abundance and low-complexity-domain interaction strength are related but distinct control variables. TRIM8-mediated turnover prevents toxic fusion accumulation. Engineered graded depletion and restoration of endogenous EWS-FLI1 produce persistent transcriptional changes and increased metastatic behavior at intermediate depletion in preclinical models. This does not establish a clinical hazard of a particular inhibitor dose. Independently of those engineered perturbations, single-cell profiling of patient tumors associates an intermediate range of inferred fusion activity with proliferation and oxidative phosphorylation, and cells on either side of that range with a hypoxia program. That is a cross-sectional association in tumors, not a demonstration that fusion dose sets the program.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-ews-fli1-dosage-and-state-plasticity","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:EZH2-Associated%20Differentiation%20Repression","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"EZH2-Associated Differentiation Repression","description":"EWS-FLI1 induces EZH2, which contributes to repression of differentiation-associated genes and maintenance of an undifferentiated state. Genetic depletion impairs clonogenicity and tumorigenicity in preclinical systems. This dependency is distinct from the heterogeneous PRC2 changes following STAG2 loss and does not imply that every Ewing tumor will respond to an EZH2 inhibitor.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-ezh2-associated-differentiation-repression","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:GGAA%20Microsatellite%20Enhancer%20Reprogramming","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"GGAA Microsatellite Enhancer Reprogramming","description":"EWS-FLI1 binds GGAA microsatellite repeats and canonical ETS motifs, remodeling the enhancer landscape. At GGAA repeats, multimeric EWS-FLI1 opens chromatin and creates de novo enhancers that contact target promoters; at conserved ETS enhancers, EWS-FLI1 can displace wild-type ETS factors and repress tumor suppressor and lineage-regulatory programs.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-ggaa-microsatellite-enhancer-reprogramming","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:NuRD-LSD1%20Transcriptional%20Repression","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"NuRD-LSD1 Transcriptional Repression","description":"EWS-FLI1 recruits NuRD-associated HDAC and LSD1 activities to repress tumor-suppressive and lineage-regulatory genes. Repression contributes to transformation alongside enhancer activation. CHD4 also maintains global chromatin architecture and survival, but this distinct dependency should not be equated with regulation of EWS-FLI1 transcriptional output.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-nurd-lsd1-transcriptional-repression","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:PARP1-Supported%20Fusion%20Transcription","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"PARP1-Supported Fusion Transcription","description":"PARP1 interacts with EWS-FLI1 and EWS-ERG and supports fusion-mediated transcription; EWS-FLI1 also maintains PARP1 expression. This experimentally reported feedback connects transcription and damage response. The preclinical drug rationale has not translated into uniform clinical response.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-parp1-supported-fusion-transcription","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:Proposed%20POLQ%20Splicing%20and%20MMEJ%20Defect","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Proposed POLQ Splicing and MMEJ Defect","description":"A 2025 bioRxiv preprint reports that EWS-FLI1 expression or EWSR1 loss induces POLQ exon 25 skipping, reduces polymerase theta protein, and impairs microhomology-mediated end joining. Fusion knockdown and POLQ rescue support causality in tested models. Proposed synthetic lethality with other repair pathways requires independent replication and clinical evaluation; this is an emerging additional repair defect rather than a reason to erase the BRCA1 literature.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-proposed-polq-splicing-and-mmej-defect","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:SLFN11-Dependent%20Replication%20Fork%20Arrest","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"SLFN11-Dependent Replication Fork Arrest","description":"EWS-FLI1 directly increases SLFN11 expression. SLFN11 blocks stressed replication forks and promotes susceptibility to DNA-damaging agents. Expression-outcome correlations are not a validated standalone clinical selection test. Loss of SLFN11 can confer treatment resistance and is associated with metabolic adaptation in Ewing models.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-slfn11-dependent-replication-fork-arrest","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:Transcription-Coupled%20R-loop%20Accumulation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Transcription-Coupled R-loop Accumulation","description":"EWS-FLI1-driven transcription and impaired regulation of damage-induced transcription promote RNA:DNA hybrids and replication stress in Ewing cell models. The stress state creates DNA-damage vulnerabilities and dependence on buffering pathways. 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Early p.Val60Leu experiments found absent ATP-evoked current and reduced ATP-stimulated dye uptake. Subsequent studies found constitutive ATP-insensitive conductance for p.Val60Leu and ATP-responsive p.Gly353Arg channels with altered sensitivity, rectification and ion selectivity. In 2025, p.Val60Leu showed fluorescent-ATP binding, small ATP-evoked currents and reduced cell viability; constitutive activity was not reproduced under those conditions. These findings support abnormal gating and coupling rather than universally absent channels or ATP binding.\nWild-type/mutant coexpression reduced permeability in the original study, but a later coexpression study retained robust ATP responses and argued against poisoning of wild-type P2X2. The dominant clinical inheritance is established for these alleles; its precise molecular basis remains disputed. P2X2/P2X3 heteromer experiments are distinct from mutant/wild-type P2X2 coexpression. Functional abnormalities of the uncertain p.Asp201Tyr/p.Asp273Tyr variant do not independently prove human disease causality.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_41.html#pathophysiology-variant-specific-p2x2-channel-dysfunction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3AAutosomal_Dominant_Nonsyndromic_Hearing_Loss_41:pathophysiology:Inner%20Hair%20Cell%20and%20Ribbon%20Synapse%20Disorganisation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Inner Hair Cell and Ribbon Synapse Disorganisation","description":"Heterozygous p.Val61Leu mice show shortened inner hair cells and abnormal perinuclear positioning of ribbon synapses. Early abnormalities occurred without overt hair-cell loss; ribbon counts were increased at four months rather than simply depleted. Later degeneration was documented in the genome-editing study. These model findings are not established human temporal-bone pathology.\nThe knockout noise experiments independently measured loss of ribbon-synapse puncta and afferent terminals after intense exposure. Noise-induced synapse attrition and spontaneous knock-in ribbon mislocalization are distinct findings. Their molecular connection to altered P2X2 gating remains uncertain.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_41.html#pathophysiology-inner-hair-cell-and-ribbon-synapse-disorganisation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3AAutosomal_Dominant_Nonsyndromic_Hearing_Loss_41:pathophysiology:Loss%20of%20Purinergic%20Adaptation%20to%20Elevated%20Sound%20Levels","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Loss of Purinergic Adaptation to Elevated Sound Levels","description":"P2rx2-null mice lack the purinergic component of adaptation to sustained sound. Under the studied 85 dB SPL noise protocols, wild-type mice developed temporary ABR threshold shifts and reduced cochlear gain, whereas null mice showed greatly reduced adaptation. At higher levels, other processes contributed to temporary threshold shifts and null mice were more susceptible to permanent loss. These protocols do not establish a human safe-exposure threshold or imply that all temporary hearing changes are noninjurious.\nATP-induced cochlear partition conductance and endocochlear-potential changes were absent in null mice. The acute cation shunt alone does not explain the prolonged threshold recovery; downstream processes remain incompletely defined. Heterozygous null littermates retained adaptation, supporting haplosufficiency in this assay. Extrapolation to heterozygous human missense disease therefore requires allele-specific testing.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_41.html#pathophysiology-loss-of-purinergic-adaptation-to-elevated-sound-levels","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"}],"edges":[{"id":"model-link:0:model:kb/disorders/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_41.yaml:Human p.Val60Leu hiPSC Allele-Selective Editing","source_id":"model:kb/disorders/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_41.yaml:Human p.Val60Leu hiPSC Allele-Selective Editing","target_id":"node:disorder%3AAutosomal_Dominant_Nonsyndromic_Hearing_Loss_41:pathophysiology:Variant-Specific%20P2X2%20Channel%20Dysfunction","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Perturbs","directed":false,"relationship":"PERTURBS","fidelity":"UNKNOWN","causal_link_type":null,"causal_link_type_label":null,"description":"Allele-selective disruption targets the variant underlying the channel-dysfunction node.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AAutosomal_Dominant_Nonsyndromic_Hearing_Loss_41:0:1","source_id":"node:disorder%3AAutosomal_Dominant_Nonsyndromic_Hearing_Loss_41:pathophysiology:Variant-Specific%20P2X2%20Channel%20Dysfunction","target_id":"node:disorder%3AAutosomal_Dominant_Nonsyndromic_Hearing_Loss_41:pathophysiology:Inner%20Hair%20Cell%20and%20Ribbon%20Synapse%20Disorganisation","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[1]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"Inferred tissue consequence of allele-specific channel dysfunction; 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no auditory functional readout."}],"evidence_text":["NGS analysis revealed robust indel generation in cells edited with SaCas9-KKH/sgRNA-1, with an indel frequency of 37.9% ± 2.3%","Human patient-derived cell editing; no auditory functional readout."],"evidence_status":"Evidence recorded","metadata_completeness":50,"metadata_present":["Model category","Organism","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Anatomy","Cell type","Cell source","Culture system"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_41.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_41.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_41.html#experimental-model-human-p-val60leu-hipsc-allele-selective-editing","source_anchor":"experimental-model-human-p-val60leu-hipsc-allele-selective-editing"},{"id":"model:kb/disorders/Pancreatic_Ductal_Adenocarcinoma.yaml:Human PDAC Cell and Organoid RAS-Response Models","name":"Human PDAC Cell and Organoid RAS-Response Models","description":"Patient-derived PDAC organoids and established cell models permit driver-specific RMC-7977 sensitivity assays; 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These isolated epithelial systems do not reproduce the complete immune or desmoplastic microenvironment.","notes":null,"context_id":"disorder:Pancreatic_Ductal_Adenocarcinoma","context_kind":"Disorder","disease_name":"Pancreatic Ductal Adenocarcinoma","disease_synonyms":[],"disease_term":{"id":"MONDO:0005184","label":"pancreatic ductal adenocarcinoma","display_label":"pancreatic ductal adenocarcinoma","url":"http://purl.obolibrary.org/obo/MONDO_0005184"},"experimental_model_type":"ORGANOID","experimental_model_type_label":"Organoid","namo_type":"namo:Organoid","declared_namo_class_name":null,"namo_class_name":"Organoid","namo_class_label":"Organoid","namo_description":"A 3D cell culture system that self-organizes to recapitulate key structural and functional aspects of an organ or tissue","namo_docs_url":"https://monarch-initiative.github.io/namo/elements/Organoid/","namo_ontology_url":"https://w3id.org/monarch-initiative/namo/Organoid","namo_mapping_basis":"Safe mapping from DisMech category","namo_class_in_schema":true,"namo_schema_status":"Defined in NAMO schema used for this build","modality":"Cellular system","organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[{"id":"CL:0002064","label":"pancreatic acinar cell","display_label":"pancreatic acinar cell","url":"http://purl.obolibrary.org/obo/CL_0002064"}],"linked_cell_type_labels":["pancreatic acinar cell"],"cell_types":[{"id":"CL:0002064","label":"pancreatic acinar cell","display_label":"pancreatic acinar cell","url":"http://purl.obolibrary.org/obo/CL_0002064"}],"cell_type_labels":["pancreatic acinar cell"],"conditions":[],"cell_source":null,"source_category":null,"culture_system":null,"publication":"PMID:38588697","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38588697","mechanisms":[{"target":"KRAS Oncogene Activation","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Pancreatic_Ductal_Adenocarcinoma.html#pathophysiology-kras-oncogene-activation","relationship":"PERTURBS","relationship_label":"Perturbs","fidelity":"NOT_SPECIFIED","fidelity_label":"Not Specified","description":"Tests RAS-GTP-inhibitor signaling and growth response.","limitations":"Cell viability and target phosphorylation are not patient response or immune-remodeling endpoints.","biological_scale":null,"anatomy":[],"cell_types":[{"id":"CL:0002064","label":"pancreatic acinar cell","display_label":"pancreatic acinar cell","url":"http://purl.obolibrary.org/obo/CL_0002064"}],"biological_processes":[{"id":"GO:0000165","label":"MAPK cascade","display_label":"MAPK cascade","url":"http://purl.obolibrary.org/obo/GO_0000165"},{"id":"GO:0043491","label":"phosphatidylinositol 3-kinase/protein kinase B signal transduction","display_label":"phosphatidylinositol 3-kinase signaling","url":"http://purl.obolibrary.org/obo/GO_0043491"},{"id":"GO:0008283","label":"cell population proliferation","display_label":"cell population proliferation","url":"http://purl.obolibrary.org/obo/GO_0008283"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[],"evidence":[],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Pancreatic_Ductal_Adenocarcinoma","model_node_id":"model:kb/disorders/Pancreatic_Ductal_Adenocarcinoma.yaml:Human PDAC Cell and Organoid RAS-Response Models","focus_node_id":"node:disorder%3APancreatic_Ductal_Adenocarcinoma:pathophysiology:KRAS%20Oncogene%20Activation","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Pancreatic_Ductal_Adenocarcinoma.html#pathograph","nodes":[{"id":"model:kb/disorders/Pancreatic_Ductal_Adenocarcinoma.yaml:Human PDAC Cell and Organoid RAS-Response Models","kind":"experimental_model","kind_label":"NAM model","label":"Human PDAC Cell and Organoid RAS-Response Models","description":"Patient-derived PDAC organoids and established cell models permit driver-specific RMC-7977 sensitivity assays; engineered and selected cell models test bypass mechanisms. These isolated epithelial systems do not reproduce the complete immune or desmoplastic microenvironment.","url":"https://dismech.monarchinitiative.org/pages/disorders/Pancreatic_Ductal_Adenocarcinoma.html#experimental-model-human-pdac-cell-and-organoid-ras-response-models","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APancreatic_Ductal_Adenocarcinoma:pathophysiology:KRAS%20Oncogene%20Activation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"KRAS Oncogene Activation","description":"Activating KRAS variants favor persistent RAS-GTP signaling through RAF-MEK-ERK and additional effector networks, supporting proliferation, survival, metabolic rewiring and microenvironmental remodeling. G12D, G12V and G12R are common in PDAC, with allele-specific signaling and inhibitor responses. Most PDACs are KRAS-mutant; KRAS-wild-type cancers require separate driver characterization. KRAS signaling does not itself establish acquisition of a particular tumor-suppressor mutation or therapeutic inhibition.","url":"https://dismech.monarchinitiative.org/pages/disorders/Pancreatic_Ductal_Adenocarcinoma.html#pathophysiology-kras-oncogene-activation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APancreatic_Ductal_Adenocarcinoma:pathophysiology:Acinar-to-Ductal%20Metaplasia","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Acinar-to-Ductal Metaplasia","description":"Acinar cells can lose differentiated identity and adopt ductal-like programs during injury and KRAS-driven transformation. ADM is reversible in regenerative settings and is not synonymous with cancer. Persistent oncogenic signaling can channel reprogrammed cells into PanIN. Adult ductal cells can also initiate PDAC with cooperating p53 alterations in mice; the relative contribution of these origins in humans remains unresolved.","url":"https://dismech.monarchinitiative.org/pages/disorders/Pancreatic_Ductal_Adenocarcinoma.html#pathophysiology-acinar-to-ductal-metaplasia","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APancreatic_Ductal_Adenocarcinoma:pathophysiology:KRAS-Dependent%20Anabolic%20Glucose%20Metabolism","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"KRAS-Dependent Anabolic Glucose Metabolism","description":"KRAS supports glucose uptake and redirects intermediates toward anabolic pathways that sustain pancreatic tumor growth. This is a regulated metabolic program rather than a universal switch eliminating oxidative phosphorylation.","url":"https://dismech.monarchinitiative.org/pages/disorders/Pancreatic_Ductal_Adenocarcinoma.html#pathophysiology-kras-dependent-anabolic-glucose-metabolism","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APancreatic_Ductal_Adenocarcinoma:pathophysiology:KRAS-GM-CSF%20Myeloid%20Immunosuppression","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"KRAS-GM-CSF Myeloid Immunosuppression","description":"Oncogenic KRAS induces tumor-cell GM-CSF, expanding suppressive myeloid cells that constrain cytotoxic T-cell immunity in pancreatic neoplasia models. This supplies a disease-driving counterpart to the myeloid remodeling seen after KRAS inhibition.","url":"https://dismech.monarchinitiative.org/pages/disorders/Pancreatic_Ductal_Adenocarcinoma.html#pathophysiology-kras-gm-csf-myeloid-immunosuppression","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APancreatic_Ductal_Adenocarcinoma:pathophysiology:KRAS-Regulated%20Glutamine%20Redox%20Metabolism","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"KRAS-Regulated Glutamine Redox Metabolism","description":"In studied PDAC cells, glutamine-derived aspartate is routed through cytosolic GOT1, malate and pyruvate to support NADPH-dependent redox balance. Dependency varies with growth context and compensatory metabolism; this does not establish clinical efficacy of glutaminase inhibition.","url":"https://dismech.monarchinitiative.org/pages/disorders/Pancreatic_Ductal_Adenocarcinoma.html#pathophysiology-kras-regulated-glutamine-redox-metabolism","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APancreatic_Ductal_Adenocarcinoma:pathophysiology:Macropinocytic%20Protein%20Scavenging","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Macropinocytic Protein Scavenging","description":"RAS-driven macropinocytosis internalizes extracellular protein for lysosomal proteolysis and amino-acid supply. 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MRTX1133 plus USP20 inhibition and PD-1 blockade regressed tumors in preclinical models, but human tissue profiling is not evidence of clinical combination efficacy.","url":"https://dismech.monarchinitiative.org/pages/disorders/Pancreatic_Ductal_Adenocarcinoma.html#pathophysiology-usp20-cholesterol-metabolism-cd8-exhaustion-checkpoint","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"}],"edges":[{"id":"model-link:0:model:kb/disorders/Pancreatic_Ductal_Adenocarcinoma.yaml:Human PDAC Cell and Organoid RAS-Response Models","source_id":"model:kb/disorders/Pancreatic_Ductal_Adenocarcinoma.yaml:Human PDAC Cell and Organoid RAS-Response 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The node is therefore named for a functional deficiency of the escortin, not for absence of the protein and not for reduced gene dosage - there is no second allele to be dosed, and the biochemistry shows a normally folded product.","url":"https://dismech.monarchinitiative.org/pages/disorders/Diamond-Blackfan_Anemia_14_with_Mandibulofacial_Dysostosis.html#pathophysiology-tsr2-escortin-deficiency","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ADiamond-Blackfan_Anemia_14_With_Mandibulofacial_Dysostosis:pathophysiology:Impaired%20Escortin%20Handover%20of%20eS26","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Escortin Handover of eS26","description":"TSR2 does three things in sequence: it dissociates the importin:eS26 complex on the nuclear side by a RanGTP-independent route, it binds and shields the released eS26 from proteolysis, and it delivers it to the 90S pre-ribosome. The disease allele is impaired at the binding step - it holds eS26 and the eukaryote-specific segment that recruits it less tightly - which puts every downstream step of the handover at risk. What has not been measured is which of the three steps fails first in a patient cell; the pathway description is from yeast and reconstituted human proteins.","url":"https://dismech.monarchinitiative.org/pages/disorders/Diamond-Blackfan_Anemia_14_with_Mandibulofacial_Dysostosis.html#pathophysiology-impaired-escortin-handover-of-es26","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Diamond-Blackfan_Anemia_14_With_Mandibulofacial_Dysostosis.yaml:Humanized yeast expressing hTsr2 E64G","source_id":"model:kb/disorders/Diamond-Blackfan_Anemia_14_With_Mandibulofacial_Dysostosis.yaml:Humanized yeast expressing hTsr2 E64G","target_id":"node:disorder%3ADiamond-Blackfan_Anemia_14_With_Mandibulofacial_Dysostosis:pathophysiology:TSR2%20Escortin%20Deficiency","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"The binding assays use recombinant human Tsr2 and human eS26, so for this node the model is not really yeast at all - it is human proteins in vitro, and it reproduces the molecular lesion directly.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ADiamond-Blackfan_Anemia_14_With_Mandibulofacial_Dysostosis:0:0","source_id":"node:disorder%3ADiamond-Blackfan_Anemia_14_With_Mandibulofacial_Dysostosis:pathophysiology:TSR2%20Escortin%20Deficiency","target_id":"node:disorder%3ADiamond-Blackfan_Anemia_14_With_Mandibulofacial_Dysostosis:pathophysiology:Impaired%20Escortin%20Handover%20of%20eS26","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[0]","label":"Causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":null,"causal_link_type_label":null,"description":"Weakened cargo binding is the proximal cause of a failed handover.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0}]}},{"target":"Defective Small-Subunit Maturation and 18S rRNA Processing","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Diamond-Blackfan_Anemia_14_with_Mandibulofacial_Dysostosis.html#pathophysiology-defective-small-subunit-maturation-and-18s-rrna-processing","relationship":"PARTIALLY_RECAPITULATES","relationship_label":"Partially Recapitulates","fidelity":"LOW","fidelity_label":"Low","description":"Yeast expressing the human disease allele grow poorly and accumulate immature 20S pre-rRNA in the cytoplasm, and excess eS26 rescues the growth defect - which is what ties the phenotype to eS26 supply rather than to some other consequence of expressing a human protein in yeast.","limitations":"The host is yeast, and the yeast Tsr2 is repressed rather than deleted, so the assay reads a humanized replacement under a heterologous promoter. The yeast intermediate is 20S pre-rRNA; the human counterpart is 18S-E, and no equivalent measurement has been made in a DBA14 patient cell. Yeast has neither erythropoiesis nor a pharyngeal arch, so the model cannot speak to either arm of the human phenotype.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0030490","label":"maturation of SSU-rRNA","display_label":"maturation of SSU-rRNA","url":"http://purl.obolibrary.org/obo/GO_0030490"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Cytoplasmic 20S pre-rRNA by FISH","description":null,"target":"Defective Small-Subunit Maturation and 18S rRNA Processing","direction":"INCREASED","interpretation":"Accumulation of the immature precursor in the cytoplasm is the standard readout of stalled small-subunit maturation.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:30201955","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30201955","reference_title":"Molecular basis for disassembly of an importin:ribosomal protein complex by the escortin Tsr2.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Tsr2 DBA mutant cells (hTsr2E64G) accumulate immature 20S pre-rRNA in the cytoplasm.","explanation":"The measurement and its direction."}],"notes":null},{"name":"Growth of PGAL1-TSR2 cells expressing hTsr2E64G","description":null,"target":"Defective Small-Subunit Maturation and 18S rRNA Processing","direction":"DECREASED","interpretation":"The organism-level correlate of the maturation defect in this system.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:30201955","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30201955","reference_title":"Molecular basis for disassembly of an importin:ribosomal protein complex by the escortin Tsr2.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Yeast cells expressing hTsr2E64G were strongly growth impaired","explanation":"The growth measurement."}],"notes":null}],"evidence":[{"reference":"PMID:30201955","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30201955","reference_title":"Molecular basis for disassembly of an importin:ribosomal protein complex by the escortin Tsr2.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Tsr2 DBA mutant cells (hTsr2E64G) accumulate immature 20S pre-rRNA in the cytoplasm.","explanation":"Establishes that the humanized strain reproduces a ribosome-maturation defect, which is why it is treated as informative for this node."},{"reference":"PMID:30201955","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30201955","reference_title":"Molecular basis for disassembly of an importin:ribosomal protein complex by the escortin Tsr2.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Yeast cells expressing hTsr2E64G were strongly growth impaired","explanation":"The growth measurement."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Diamond-Blackfan_Anemia_14_With_Mandibulofacial_Dysostosis","model_node_id":"model:kb/disorders/Diamond-Blackfan_Anemia_14_With_Mandibulofacial_Dysostosis.yaml:Humanized yeast expressing hTsr2 E64G","focus_node_id":"node:disorder%3ADiamond-Blackfan_Anemia_14_With_Mandibulofacial_Dysostosis:pathophysiology:Defective%20Small-Subunit%20Maturation%20and%2018S%20rRNA%20Processing","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Diamond-Blackfan_Anemia_14_with_Mandibulofacial_Dysostosis.html#pathograph","nodes":[{"id":"model:kb/disorders/Diamond-Blackfan_Anemia_14_With_Mandibulofacial_Dysostosis.yaml:Humanized yeast expressing hTsr2 E64G","kind":"experimental_model","kind_label":"NAM model","label":"Humanized yeast expressing hTsr2 E64G","description":"A conditional PGAL1-TSR2 Saccharomyces cerevisiae strain in which yeast Tsr2 is repressed and the human protein - wild type or the DBA14 E64G variant - is supplied from a plasmid. 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In human cells the equivalent intermediate is the 18S-E pre-rRNA; the measurement available for this allele is the yeast one, and this node states it at that level.","url":"https://dismech.monarchinitiative.org/pages/disorders/Diamond-Blackfan_Anemia_14_with_Mandibulofacial_Dysostosis.html#pathophysiology-defective-small-subunit-maturation-and-18s-rrna-processing","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ADiamond-Blackfan_Anemia_14_With_Mandibulofacial_Dysostosis:pathophysiology:Abnormal%20Craniofacial%20Embryonic%20Development","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Abnormal Craniofacial Embryonic Development","description":"Both affected males have a mandibulofacial dysostosis: derivatives of the first and second pharyngeal arches and the external ear are hypoplastic or absent. What produces it is unresolved. In Treacher Collins syndrome, the craniofacial ribosomopathy this phenotype most resembles, the lesion is referred to cranial neural crest; nothing analogous has been shown for TSR2, and this node deliberately stops at \"abnormal embryologic development\", the level the gene-discovery paper states. See the `tsr2-craniofacial-mechanism` discussion.","url":"https://dismech.monarchinitiative.org/pages/disorders/Diamond-Blackfan_Anemia_14_with_Mandibulofacial_Dysostosis.html#pathophysiology-abnormal-craniofacial-embryonic-development","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ADiamond-Blackfan_Anemia_14_With_Mandibulofacial_Dysostosis:pathophysiology:Deficient%20eS26%20Incorporation%20into%20the%20Small%20Ribosomal%20Subunit","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Deficient eS26 Incorporation into the Small Ribosomal Subunit","description":"The consequence of a failed handover is a shortfall of eS26 on the assembling 40S subunit. This is the node at which DBA14 converges on DBA10: RPS26 haploinsufficiency reaches the same state by halving the supply of the protein, while TSR2 deficiency reaches it by failing to deliver a normal supply. That convergence is an inference from the two genes' shared biology and is not something anyone has measured in a DBA14 patient cell.","url":"https://dismech.monarchinitiative.org/pages/disorders/Diamond-Blackfan_Anemia_14_with_Mandibulofacial_Dysostosis.html#pathophysiology-deficient-es26-incorporation-into-the-small-ribosomal-subunit","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ADiamond-Blackfan_Anemia_14_With_Mandibulofacial_Dysostosis:pathophysiology:Impaired%20Erythroid%20Progenitor%20Output","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Erythroid Progenitor Output","description":"Erythroid progenitors are the compartment that fails in DBA, producing a normochromic macrocytic anemia with reticulocytopenia while leukocytes and platelets are preserved. In the TSR2 kindred the severity of this node differs between the two carriers of the same allele: one required steroid treatment from ten months, the other never had overt anemia and showed only the biochemical markers.","url":"https://dismech.monarchinitiative.org/pages/disorders/Diamond-Blackfan_Anemia_14_with_Mandibulofacial_Dysostosis.html#pathophysiology-impaired-erythroid-progenitor-output","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ADiamond-Blackfan_Anemia_14_With_Mandibulofacial_Dysostosis:pathophysiology:Ribosomal%20Stress%20Response","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Ribosomal Stress Response","description":"Impaired ribosome biogenesis in DBA activates p53 and a set of associated responses - translational dysfunction, inflammation, imbalanced globin and heme synthesis, autophagy dysregulation - that converge on the erythroid compartment. This node is curated at the level of the DBA class. Nobody has measured p53 activation, or any of the rest of it, in a TSR2-mutant cell, so the node carries the class-level claim and says so rather than being dropped: it is the step that connects a general biogenesis defect to a selectively erythroid outcome, and leaving it out would make the pathograph look better evidenced than it is.","url":"https://dismech.monarchinitiative.org/pages/disorders/Diamond-Blackfan_Anemia_14_with_Mandibulofacial_Dysostosis.html#pathophysiology-ribosomal-stress-response","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:1:model:kb/disorders/Diamond-Blackfan_Anemia_14_With_Mandibulofacial_Dysostosis.yaml:Humanized yeast expressing hTsr2 E64G","source_id":"model:kb/disorders/Diamond-Blackfan_Anemia_14_With_Mandibulofacial_Dysostosis.yaml:Humanized yeast expressing hTsr2 E64G","target_id":"node:disorder%3ADiamond-Blackfan_Anemia_14_With_Mandibulofacial_Dysostosis:pathophysiology:Defective%20Small-Subunit%20Maturation%20and%2018S%20rRNA%20Processing","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[1]","label":"Partially Recapitulates","directed":false,"relationship":"PARTIALLY_RECAPITULATES","fidelity":"LOW","causal_link_type":null,"causal_link_type_label":null,"description":"Yeast expressing the human disease allele grow poorly and accumulate immature 20S pre-rRNA in the cytoplasm, and excess eS26 rescues the growth defect - which is what ties the phenotype to eS26 supply rather than to some other consequence of expressing a human protein in yeast.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ADiamond-Blackfan_Anemia_14_With_Mandibulofacial_Dysostosis:3:2","source_id":"node:disorder%3ADiamond-Blackfan_Anemia_14_With_Mandibulofacial_Dysostosis:pathophysiology:Defective%20Small-Subunit%20Maturation%20and%2018S%20rRNA%20Processing","target_id":"node:disorder%3ADiamond-Blackfan_Anemia_14_With_Mandibulofacial_Dysostosis:pathophysiology:Abnormal%20Craniofacial%20Embryonic%20Development","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[3].downstream[2]","label":"Causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":null,"causal_link_type_label":null,"description":"The craniofacial arm. Same standing as the erythroid edge: the source states abnormal embryologic development as a consequence of impeded ribosome biogenesis without identifying the cell population involved.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ADiamond-Blackfan_Anemia_14_With_Mandibulofacial_Dysostosis:3:1","source_id":"node:disorder%3ADiamond-Blackfan_Anemia_14_With_Mandibulofacial_Dysostosis:pathophysiology:Defective%20Small-Subunit%20Maturation%20and%2018S%20rRNA%20Processing","target_id":"node:disorder%3ADiamond-Blackfan_Anemia_14_With_Mandibulofacial_Dysostosis:pathophysiology:Impaired%20Erythroid%20Progenitor%20Output","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[3].downstream[1]","label":"Causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":null,"causal_link_type_label":null,"description":"The erythroid arm of the phenotype. The step is asserted at the level the gene-discovery paper asserts it - defective erythropoiesis as a consequence of impeded ribosome biogenesis - not at the level of a measured erythroid defect in a DBA14 cell.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ADiamond-Blackfan_Anemia_14_With_Mandibulofacial_Dysostosis:3:0","source_id":"node:disorder%3ADiamond-Blackfan_Anemia_14_With_Mandibulofacial_Dysostosis:pathophysiology:Defective%20Small-Subunit%20Maturation%20and%2018S%20rRNA%20Processing","target_id":"node:disorder%3ADiamond-Blackfan_Anemia_14_With_Mandibulofacial_Dysostosis:pathophysiology:Ribosomal%20Stress%20Response","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[3].downstream[0]","label":"Causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":null,"causal_link_type_label":null,"description":"Stalled subunit maturation is the canonical trigger of the ribosomal stress response in the ribosomopathies.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ADiamond-Blackfan_Anemia_14_With_Mandibulofacial_Dysostosis:2:0","source_id":"node:disorder%3ADiamond-Blackfan_Anemia_14_With_Mandibulofacial_Dysostosis:pathophysiology:Deficient%20eS26%20Incorporation%20into%20the%20Small%20Ribosomal%20Subunit","target_id":"node:disorder%3ADiamond-Blackfan_Anemia_14_With_Mandibulofacial_Dysostosis:pathophysiology:Defective%20Small-Subunit%20Maturation%20and%2018S%20rRNA%20Processing","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[0]","label":"Causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":null,"causal_link_type_label":null,"description":"A subunit missing eS26 does not complete maturation on schedule.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0}]}},{"target":"Deficient eS26 Incorporation into the Small Ribosomal Subunit","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Diamond-Blackfan_Anemia_14_with_Mandibulofacial_Dysostosis.html#pathophysiology-deficient-es26-incorporation-into-the-small-ribosomal-subunit","relationship":"RESCUES","relationship_label":"Rescues","fidelity":"LOW","fidelity_label":"Low","description":"The eS26-overexpression arm. 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This is the only system in which the human disease allele has been tested functionally, and it carries the whole weight of the functional argument for pathogenicity. Its readouts are growth, cytoplasmic accumulation of the immature 20S pre-rRNA, and direct binding of recombinant human Tsr2 to human eS26.","url":"https://dismech.monarchinitiative.org/pages/disorders/Diamond-Blackfan_Anemia_14_with_Mandibulofacial_Dysostosis.html#experimental-model-humanized-yeast-expressing-htsr2-e64g","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ADiamond-Blackfan_Anemia_14_With_Mandibulofacial_Dysostosis:pathophysiology:Deficient%20eS26%20Incorporation%20into%20the%20Small%20Ribosomal%20Subunit","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Deficient eS26 Incorporation into the Small Ribosomal Subunit","description":"The consequence of a failed handover is a shortfall of eS26 on the assembling 40S subunit. 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That convergence is an inference from the two genes' shared biology and is not something anyone has measured in a DBA14 patient cell.","url":"https://dismech.monarchinitiative.org/pages/disorders/Diamond-Blackfan_Anemia_14_with_Mandibulofacial_Dysostosis.html#pathophysiology-deficient-es26-incorporation-into-the-small-ribosomal-subunit","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ADiamond-Blackfan_Anemia_14_With_Mandibulofacial_Dysostosis:pathophysiology:Defective%20Small-Subunit%20Maturation%20and%2018S%20rRNA%20Processing","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Defective Small-Subunit Maturation and 18S rRNA Processing","description":"Cells expressing the human disease allele accumulate immature 20S pre-rRNA in the cytoplasm, the classic readout of a stalled small-subunit maturation pathway, and grow poorly. 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The disease allele is impaired at the binding step - it holds eS26 and the eukaryote-specific segment that recruits it less tightly - which puts every downstream step of the handover at risk. What has not been measured is which of the three steps fails first in a patient cell; the pathway description is from yeast and reconstituted human proteins.","url":"https://dismech.monarchinitiative.org/pages/disorders/Diamond-Blackfan_Anemia_14_with_Mandibulofacial_Dysostosis.html#pathophysiology-impaired-escortin-handover-of-es26","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:2:model:kb/disorders/Diamond-Blackfan_Anemia_14_With_Mandibulofacial_Dysostosis.yaml:Humanized yeast expressing hTsr2 E64G","source_id":"model:kb/disorders/Diamond-Blackfan_Anemia_14_With_Mandibulofacial_Dysostosis.yaml:Humanized yeast expressing hTsr2 E64G","target_id":"node:disorder%3ADiamond-Blackfan_Anemia_14_With_Mandibulofacial_Dysostosis:pathophysiology:Deficient%20eS26%20Incorporation%20into%20the%20Small%20Ribosomal%20Subunit","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[2]","label":"Rescues","directed":false,"relationship":"RESCUES","fidelity":"LOW","causal_link_type":null,"causal_link_type_label":null,"description":"The eS26-overexpression arm. 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biogenesis"],"pathway_terms":[],"pathways":[],"gene_terms":[{"id":"hgnc:25455","label":"TSR2","display_label":"TSR2","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/25455"}],"genes":["TSR2"],"chemical_terms":[],"chemicals":[],"readout_names":["Binding of human eS26 to immobilised GST-hTsr2","Far-UV circular dichroism spectra of wild-type and E64G human Tsr2","Cytoplasmic 20S pre-rRNA by FISH","Growth of PGAL1-TSR2 cells expressing hTsr2E64G","Growth of hTsr2E64G cells with eS26 overexpression"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:30201955","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30201955","reference_title":"Molecular basis for disassembly of an importin:ribosomal protein complex by the escortin Tsr2.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Notably, a Diamond-Blackfan anemia-associated Tsr2 mutant protein is impaired in binding to ESS, unveiling a critical role for this interaction in human hematopoiesis.","explanation":"The authors' own statement that the disease-associated protein is the one they characterised, which is what makes this model informative for this node."},{"reference":"PMID:30201955","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30201955","reference_title":"Molecular basis for disassembly of an importin:ribosomal protein complex by the escortin Tsr2.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Binding to human eS26 is weaker for hTsr2E64G mutant than the WT","explanation":"The measurement itself, in the stated direction."},{"reference":"PMID:30201955","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30201955","reference_title":"Molecular basis for disassembly of an importin:ribosomal protein complex by the escortin Tsr2.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"This weaker interaction is not due to perturbed folding of hTsr2E64G since far-UV circular dichroism (CD) measurements revealed identical secondary structure content for mutant and WT proteins","explanation":"Reports the unchanged secondary-structure content and draws the inference this readout records."},{"reference":"PMID:30201955","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30201955","reference_title":"Molecular basis for disassembly of an importin:ribosomal protein complex by the escortin Tsr2.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Tsr2 DBA mutant cells (hTsr2E64G) accumulate immature 20S pre-rRNA in the cytoplasm.","explanation":"Establishes that the humanized strain reproduces a ribosome-maturation defect, which is why it is treated as informative for this node."},{"reference":"PMID:30201955","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30201955","reference_title":"Molecular basis for disassembly of an importin:ribosomal protein complex by the escortin Tsr2.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Yeast cells expressing hTsr2E64G were strongly growth impaired","explanation":"The growth measurement."},{"reference":"PMID:30201955","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30201955","reference_title":"Molecular basis for disassembly of an importin:ribosomal protein complex by the escortin Tsr2.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Overexpression of eS26 rescues from the impaired growth.","explanation":"The rescue is what makes this system informative about eS26 incorporation specifically rather than about TSR2 in general."}],"evidence_text":["Notably, a Diamond-Blackfan anemia-associated Tsr2 mutant protein is impaired in binding to ESS, unveiling a critical role for this interaction in human hematopoiesis.","Binding to human eS26 is weaker for hTsr2E64G mutant than the WT","This weaker interaction is not due to perturbed folding of hTsr2E64G since far-UV circular 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category","Organism","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Anatomy","Cell type","Cell source","Culture system"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Diamond-Blackfan_Anemia_14_With_Mandibulofacial_Dysostosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Diamond-Blackfan_Anemia_14_With_Mandibulofacial_Dysostosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Diamond-Blackfan_Anemia_14_with_Mandibulofacial_Dysostosis.html#experimental-model-humanized-yeast-expressing-htsr2-e64g","source_anchor":"experimental-model-humanized-yeast-expressing-htsr2-e64g"},{"id":"model:kb/disorders/Congenital_Heart_Disease.yaml:Hypoplastic left heart syndrome patient-derived iPSC-cardiomyocytes","name":"Hypoplastic left heart syndrome patient-derived 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Among SASP-related factors, TGF-β plays an exclusive role in promoting lung fibroblast-to-myofibroblast differentiation. Moreover, the autocrine TGF-β-positive feedback loop in AT2-lineage cells is a critical cellular system in non-inflammatory lung fibrogenesis.","explanation":"The immune-cell-free organoid experiment establishes epithelial-fibroblast sufficiency under bleomycin stimulation; accompanying mouse genetics do not imply immune independence of whole-animal disease."}],"evidence_text":["Here, we establish an organoid-based lung fibrosis model using mouse and human lung tissues to assess the direct communication between damaged alveolar type II (AT2)-lineage cells and lung fibroblasts by excluding immune cells.","bleomycin causes DNA damage and activates p53 signaling in AT2-lineage cells, leading to AT2-to-AT1 transition-like state with a senescence-associated secretory phenotype (SASP). Among SASP-related factors, TGF-β plays an exclusive role in promoting lung fibroblast-to-myofibroblast differentiation. Moreover, the autocrine TGF-β-positive feedback loop in AT2-lineage cells is a critical cellular system in non-inflammatory lung fibrogenesis.","The co-culture removes immune cells to isolate epithelial-mesenchymal communication.","The immune-cell-free organoid experiment establishes epithelial-fibroblast sufficiency under bleomycin stimulation; accompanying mouse genetics do not imply immune independence of whole-animal disease."],"evidence_status":"Evidence recorded","metadata_completeness":80,"metadata_present":["Model category","NAMO class","Anatomy","Cell type","Cell source","Modeled mechanism","Publication","Evidence"],"metadata_missing":["Organism","Culture system"],"dataset_context":"Available in same entry","context_dataset_ids":["dataset:ega:egas00001004758","dataset:ega:egas00001005794","dataset:geo:gse262882","dataset:geo:gse314583","dataset:massive:msv000093453","dataset:massive:msv000094806","dataset:massive:msv000098032","dataset:scea:e-curd-126"],"candidate_dataset_ids":[],"source_path":"kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Idiopathic_Pulmonary_Fibrosis.html#experimental-model-immune-cell-free-at2-lineage-and-fibroblast-organoids","source_anchor":"experimental-model-immune-cell-free-at2-lineage-and-fibroblast-organoids"},{"id":"model:kb/disorders/Influenza.yaml:Immune-competent microvascularized lung-on-a-chip (IC-LOC) severe H1N1 model","name":"Immune-competent microvascularized lung-on-a-chip (IC-LOC) severe H1N1 model","description":"A microvascularized human small-airway chip carrying both tissue-resident (alveolar macrophage, dendritic cell, interstitial macrophage) and circulating immune populations alongside airway epithelium and stromal fibroblasts. 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Its distinctive result is a dissociation that a cytokine panel alone would not reveal: IL-1beta and TNF-alpha, usually grouped together as pro-inflammatory drivers, act in opposite directions on the storm.","notes":null,"context_id":"disorder:Influenza","context_kind":"Disorder","disease_name":"Influenza","disease_synonyms":[],"disease_term":{"id":"MONDO:0005812","label":"influenza","display_label":"influenza","url":"http://purl.obolibrary.org/obo/MONDO_0005812"},"experimental_model_type":"ORGAN_ON_CHIP","experimental_model_type_label":"Organ-on-chip","namo_type":"namo:OrganOnChip","declared_namo_class_name":"OrganOnChip","namo_class_name":"OrganOnChip","namo_class_label":"Organ On Chip","namo_description":"A model system that simulates the physiological functions of an organ using a microfluidic device. Examples: Airway-on-chip, ... Aligned with ISO 10991:2023 microfluidics terminology.","namo_docs_url":"https://monarch-initiative.github.io/namo/elements/OrganOnChip/","namo_ontology_url":"https://w3id.org/monarch-initiative/namo/OrganOnChip","namo_mapping_basis":"Explicit in DisMech","namo_class_in_schema":true,"namo_schema_status":"Defined in NAMO schema used for this build","modality":"Microphysiological system","organism":{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},"organism_label":"Homo sapiens","model_tissue":[{"id":"UBERON:0002051","label":"epithelium of bronchiole","display_label":"epithelium of bronchiole","url":"http://purl.obolibrary.org/obo/UBERON_0002051"}],"model_tissue_labels":["epithelium of bronchiole"],"linked_anatomy":[{"id":"UBERON:0002048","label":"lung","display_label":"lung","url":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"UBERON:0001004","label":"respiratory system","display_label":"respiratory system","url":"http://purl.obolibrary.org/obo/UBERON_0001004"}],"linked_anatomy_labels":["lung","respiratory system"],"anatomy":[{"id":"UBERON:0002051","label":"epithelium of bronchiole","display_label":"epithelium of bronchiole","url":"http://purl.obolibrary.org/obo/UBERON_0002051"},{"id":"UBERON:0002048","label":"lung","display_label":"lung","url":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"UBERON:0001004","label":"respiratory system","display_label":"respiratory system","url":"http://purl.obolibrary.org/obo/UBERON_0001004"}],"anatomy_labels":["epithelium of bronchiole","lung","respiratory system"],"tissue_label":"epithelium of bronchiole","model_cell_types":[{"id":"CL:0002328","label":"bronchial epithelial cell","display_label":"Bronchial epithelial cell","url":"http://purl.obolibrary.org/obo/CL_0002328"},{"id":"CL:0000583","label":"alveolar macrophage","display_label":"Alveolar macrophage","url":"http://purl.obolibrary.org/obo/CL_0000583"},{"id":"CL:0002553","label":"fibroblast of lung","display_label":"Lung fibroblast","url":"http://purl.obolibrary.org/obo/CL_0002553"}],"model_cell_type_labels":["bronchial epithelial cell","alveolar macrophage","fibroblast of lung"],"linked_cell_types":[{"id":"CL:0000235","label":"macrophage","display_label":"macrophage","url":"http://purl.obolibrary.org/obo/CL_0000235"},{"id":"CL:0002632","label":"epithelial cell of lower respiratory tract","display_label":"respiratory epithelial cell","url":"http://purl.obolibrary.org/obo/CL_0002632"},{"id":"CL:0000583","label":"alveolar macrophage","display_label":"alveolar macrophage","url":"http://purl.obolibrary.org/obo/CL_0000583"}],"linked_cell_type_labels":["macrophage","epithelial cell of lower respiratory tract","alveolar macrophage"],"cell_types":[{"id":"CL:0002328","label":"bronchial epithelial cell","display_label":"Bronchial epithelial cell","url":"http://purl.obolibrary.org/obo/CL_0002328"},{"id":"CL:0000583","label":"alveolar macrophage","display_label":"Alveolar macrophage","url":"http://purl.obolibrary.org/obo/CL_0000583"},{"id":"CL:0002553","label":"fibroblast of lung","display_label":"Lung fibroblast","url":"http://purl.obolibrary.org/obo/CL_0002553"},{"id":"CL:0000235","label":"macrophage","display_label":"macrophage","url":"http://purl.obolibrary.org/obo/CL_0000235"},{"id":"CL:0002632","label":"epithelial cell of lower respiratory tract","display_label":"respiratory epithelial cell","url":"http://purl.obolibrary.org/obo/CL_0002632"}],"cell_type_labels":["bronchial epithelial cell","alveolar macrophage","fibroblast of lung","macrophage","epithelial cell of lower respiratory tract"],"conditions":["influenza A H1N1 infection (MOI 10, severe)","IL-1beta inhibition (canakinumab)","TNF-alpha inhibition (infliximab)","CXCR4 inhibition (AMD3100)","oseltamivir"],"cell_source":null,"source_category":null,"culture_system":"Microvascularized immune-competent lung-on-a-chip with airway and interstitial compartments","publication":"PMID:40987954","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40987954","mechanisms":[{"target":"Inflammasome Activation and Cytokine Storm","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Influenza.html#pathophysiology-inflammasome-activation-and-cytokine-storm","relationship":"RECAPITULATES","relationship_label":"Recapitulates","fidelity":"HIGH","fidelity_label":"High","description":"Severe H1N1 infection produced airway and interstitial cytokine profiles matching those measured in bronchoalveolar lavage fluid from patients with severe influenza. 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It carries no adaptive memory, no systemic organ crosstalk, and a single donor genotype per device, so it cannot address host-genetic variation in severity.","biological_scale":null,"anatomy":[],"cell_types":[{"id":"CL:0000235","label":"macrophage","display_label":"macrophage","url":"http://purl.obolibrary.org/obo/CL_0000235"}],"biological_processes":[{"id":"GO:0070269","label":"pyroptotic inflammatory response","display_label":"pyroptotic inflammatory response","url":"http://purl.obolibrary.org/obo/GO_0070269"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Airway and interstitial pro-inflammatory cytokine secretion","description":null,"target":"Inflammasome Activation and Cytokine Storm","direction":"INCREASED","interpretation":"Cytokine elevation matching patient lavage fluid is the primary evidence that the chip reproduces the human storm.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:40987954","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40987954","reference_title":"An immune-competent lung-on-a-chip for modelling the human severe influenza infection response.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Here we develop an immune-competent, microvascularized, human lung-on-a-chip device to model the small airways, successfully demonstrating the cytokine storm, immune cell activation, epithelial cell damage, and other cellular- and tissue-level human immune responses to severe H1N1 infection.","explanation":"Reports the cytokine storm and immune activation this readout measures."}],"notes":null},{"name":"Cytokine response to IL-1beta versus TNF-alpha blockade","description":null,"target":"Inflammasome Activation and Cytokine Storm","direction":"ALTERED","interpretation":"Opposite responses to blocking two mediators usually treated together distinguish a driver from a regulator of the storm.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:40987954","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40987954","reference_title":"An immune-competent lung-on-a-chip for modelling the human severe influenza infection response.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We find that inhibition of IL-1β completely ameliorates the observed cytokine storm, whereas TNF-α appears to be a critical regulator, as its inhibition results in a highly increased inflammatory response.","explanation":"The inhibition experiment that establishes the opposing roles."}],"notes":null}],"evidence":[{"reference":"PMID:40987954","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40987954","reference_title":"An immune-competent lung-on-a-chip for modelling the human severe influenza infection response.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We find that interleukin-1β and tumour necrosis factor-α play opposing roles in the initiation and regulation of the cytokine storm associated with severe influenza.","explanation":"Supports the chip as informative for the mechanism of the influenza cytokine storm."},{"reference":"PMID:40987954","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40987954","reference_title":"An immune-competent lung-on-a-chip for modelling the human severe influenza infection response.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Here we develop an immune-competent, microvascularized, human lung-on-a-chip device to model the small airways, successfully demonstrating the cytokine storm, immune cell activation, epithelial cell damage, and other cellular- and tissue-level human immune responses to severe H1N1 infection.","explanation":"Reports the cytokine storm and immune activation this readout 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Excessive inflammasome activation contributes to the cytokine storm associated with severe influenza.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Influenza.html#pathophysiology-inflammasome-activation-and-cytokine-storm","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Influenza.yaml:Immune-competent microvascularized lung-on-a-chip (IC-LOC) severe H1N1 model","source_id":"model:kb/disorders/Influenza.yaml:Immune-competent microvascularized lung-on-a-chip (IC-LOC) severe H1N1 model","target_id":"node:disorder%3AInfluenza:pathophysiology:Inflammasome%20Activation%20and%20Cytokine%20Storm","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"HIGH","causal_link_type":null,"causal_link_type_label":null,"description":"Severe H1N1 infection produced airway and interstitial cytokine profiles matching those measured in bronchoalveolar lavage fluid from patients with severe influenza. 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PARTIAL reflects that dependence."},{"reference":"PMID:40987954","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40987954","reference_title":"An immune-competent lung-on-a-chip for modelling the human severe influenza infection response.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Here we develop an immune-competent, microvascularized, human lung-on-a-chip device to model the small airways, successfully demonstrating the cytokine storm, immune cell activation, epithelial cell damage, and other cellular- and tissue-level human immune responses to severe H1N1 infection.","explanation":"Reports epithelial cell damage among the recapitulated responses."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"isolated","context_id":"disorder:Influenza","model_node_id":"model:kb/disorders/Influenza.yaml:Immune-competent microvascularized lung-on-a-chip (IC-LOC) severe H1N1 model","focus_node_id":"node:disorder%3AInfluenza:pathophysiology:Respiratory%20Epithelial%20Infection%20and%20Cytopathic%20Effect","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Influenza.html#pathograph","nodes":[{"id":"model:kb/disorders/Influenza.yaml:Immune-competent microvascularized lung-on-a-chip (IC-LOC) severe H1N1 model","kind":"experimental_model","kind_label":"NAM model","label":"Immune-competent microvascularized lung-on-a-chip (IC-LOC) severe H1N1 model","description":"A microvascularized human small-airway chip carrying both tissue-resident (alveolar macrophage, dendritic cell, interstitial macrophage) and circulating immune populations alongside airway epithelium and stromal fibroblasts. 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This causes direct cytopathic damage to airway epithelium, leading to desquamation, impaired mucociliary clearance, and susceptibility to secondary bacterial infection.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Influenza.html#pathophysiology-respiratory-epithelial-infection-and-cytopathic-effect","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:1:model:kb/disorders/Influenza.yaml:Immune-competent microvascularized lung-on-a-chip (IC-LOC) severe H1N1 model","source_id":"model:kb/disorders/Influenza.yaml:Immune-competent microvascularized lung-on-a-chip (IC-LOC) severe H1N1 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microvascularized human small-airway chip carrying both tissue-resident (alveolar macrophage, dendritic cell, interstitial macrophage) and circulating immune populations alongside airway epithelium and stromal fibroblasts. Infection at high multiplicity reproduces the cytokine storm of severe influenza, and single-cell RNA sequencing plus targeted inhibition were used to separate the contributions of individual mediators. Its distinctive result is a dissociation that a cytokine panel alone would not reveal: IL-1beta and TNF-alpha, usually grouped together as pro-inflammatory drivers, act in opposite directions on the storm.","url":"https://dismech.monarchinitiative.org/pages/disorders/Influenza.html#experimental-model-immune-competent-microvascularized-lung-on-a-chip-ic-loc-severe-h1n1-model","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AInfluenza:pathophysiology:Endothelial%20Dysfunction%20and%20Thromboinflammation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Endothelial Dysfunction and Thromboinflammation","description":"Severe influenza involves pulmonary microvascular endothelial infection and activation, leading to vascular leakage, adhesion molecule upregulation (ICAM-1, VCAM-1), and thromboinflammatory complications including venous thromboembolism. In critically ill influenza cohorts, VTE incidence has been reported at 9.37%.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Influenza.html#pathophysiology-endothelial-dysfunction-and-thromboinflammation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AInfluenza:pathophysiology:Triggering%20of%20Acute%20Myocardial%20Infarction","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Triggering of Acute Myocardial Infarction","description":"Acute influenza is a recognized short-term trigger of acute myocardial infarction. Influenza-driven systemic inflammation, endothelial activation, platelet activation, and a procoagulant shift can destabilize vulnerable coronary atherosclerotic plaque and precipitate atherothrombotic occlusion, with the excess risk concentrated in the first 7 days after infection. In a self-controlled case-series of laboratory-confirmed influenza, the incidence of hospitalization for acute myocardial infarction was about six-fold higher during the 7-day risk interval than during the control interval, with no increased incidence after day 7. This makes acute MI an important downstream cardiovascular sequela of influenza beyond the respiratory tract, and underpins the cardioprotective rationale for influenza vaccination.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Influenza.html#pathophysiology-triggering-of-acute-myocardial-infarction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:2:model:kb/disorders/Influenza.yaml:Immune-competent microvascularized lung-on-a-chip (IC-LOC) severe H1N1 model","source_id":"model:kb/disorders/Influenza.yaml:Immune-competent microvascularized lung-on-a-chip (IC-LOC) severe H1N1 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ones.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AInfluenza:4:0","source_id":"node:disorder%3AInfluenza:pathophysiology:Endothelial%20Dysfunction%20and%20Thromboinflammation","target_id":"node:disorder%3AInfluenza:pathophysiology:Triggering%20of%20Acute%20Myocardial%20Infarction","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[4].downstream[0]","label":"Indirectly causes (known intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_KNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Known Intermediates","description":"The acute systemic inflammatory and prothrombotic state of influenza acts as a trigger for acute myocardial infarction in the first week after infection.\n","intermediate_mechanisms":["Systemic inflammation and thromboinflammatory endothelial activation","Coronary atherosclerotic plaque instability and rupture","Platelet activation and procoagulant shift causing atherothrombotic coronary occlusion"],"hypothesis_groups":[],"evidence_count":0}]}}],"mechanism_names":["Inflammasome Activation and Cytokine Storm","Respiratory Epithelial Infection and Cytopathic Effect","Endothelial Dysfunction and Thromboinflammation"],"relationships":["Recapitulates","Measures"],"fidelities":["High","Moderate"],"biological_scales":[],"system_context_sources":["Model-level tissue","Model-level cell type","Linked mechanism anatomy","Linked mechanism cell type"],"modeled_system_labels":["epithelium of bronchiole","lung","respiratory system","bronchial epithelial cell","alveolar macrophage","fibroblast of lung","macrophage","epithelial cell of lower respiratory tract"],"biological_process_terms":[{"id":"GO:0070269","label":"pyroptotic inflammatory response","display_label":"pyroptotic inflammatory response","url":"http://purl.obolibrary.org/obo/GO_0070269"},{"id":"GO:0019079","label":"viral genome 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compartment"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:40987954","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40987954","reference_title":"An immune-competent lung-on-a-chip for modelling the human severe influenza infection response.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We find that interleukin-1β and tumour necrosis factor-α play opposing roles in the initiation and regulation of the cytokine storm associated with severe influenza.","explanation":"Supports the chip as informative for the mechanism of the influenza cytokine storm."},{"reference":"PMID:40987954","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40987954","reference_title":"An immune-competent lung-on-a-chip for modelling the human severe influenza infection response.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Here we develop an immune-competent, microvascularized, human lung-on-a-chip device to model the small airways, successfully demonstrating the cytokine storm, immune cell activation, epithelial cell damage, and other cellular- and tissue-level human immune responses to severe H1N1 infection.","explanation":"Reports the cytokine storm and immune activation this readout measures."},{"reference":"PMID:40987954","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40987954","reference_title":"An immune-competent lung-on-a-chip for modelling the human severe influenza infection response.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We find that inhibition of IL-1β completely ameliorates the observed cytokine storm, whereas TNF-α appears to be a critical regulator, as its inhibition results in a highly increased inflammatory response.","explanation":"The inhibition experiment that establishes the opposing roles."},{"reference":"PMID:40987954","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40987954","reference_title":"An immune-competent lung-on-a-chip for modelling the human severe influenza infection response.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"However, the full array of tissue-resident and circulatory immune cells is necessary to elicit a significant airway and interstitial cytokine storm in response to severe infection.","explanation":"Records that the epithelial response is only fully realized with the complete immune reconstruction; PARTIAL reflects that dependence."},{"reference":"PMID:40987954","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40987954","reference_title":"An immune-competent lung-on-a-chip for modelling the human severe influenza infection response.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Furthermore, we discover the critical stromal-immune CXCL12-CXCR4 interaction and its role in immune response to infection.","explanation":"Supports the chip as a system for measuring stromal-immune signalling in the infected lung interstitium."},{"reference":"PMID:40987954","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40987954","reference_title":"An immune-competent lung-on-a-chip for modelling the human severe influenza infection response.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"When considering the specific ligand–receptor (L–R) interactions, we found that the CXCL12–CXCR4 interaction had the largest relative contribution in the CXCL pathway, coming largely from fibroblast CXCL12","explanation":"Identifies the specific stromal-immune interaction this readout measures."}],"evidence_text":["We find that interleukin-1β and tumour necrosis factor-α play opposing roles in the initiation and regulation of the cytokine storm associated with severe influenza.","Here we develop an immune-competent, microvascularized, human lung-on-a-chip device to model the small airways, successfully demonstrating the cytokine storm, immune cell activation, epithelial cell damage, and other cellular- and tissue-level human immune responses to severe H1N1 infection.","We find that inhibition of IL-1β completely ameliorates the observed cytokine storm, whereas TNF-α appears to be a critical regulator, as its inhibition results in a highly increased inflammatory response.","However, the full array of tissue-resident and circulatory immune cells is necessary to elicit a significant airway and interstitial cytokine storm in response to severe infection.","Furthermore, we discover the critical stromal-immune CXCL12-CXCR4 interaction and its role in immune response to infection.","When considering the specific ligand–receptor (L–R) interactions, we found that the CXCL12–CXCR4 interaction had the largest relative contribution in the CXCL pathway, coming largely from fibroblast CXCL12","Supports the chip as informative for the mechanism of the influenza cytokine storm.","Reports the cytokine storm and immune activation this readout measures.","The inhibition experiment that establishes the opposing roles.","Records that the epithelial response is only fully realized with the complete immune reconstruction; PARTIAL reflects that dependence.","Supports the chip as a system for measuring stromal-immune signalling in the infected lung interstitium.","Identifies the specific stromal-immune interaction this readout measures."],"evidence_status":"Evidence recorded","metadata_completeness":90,"metadata_present":["Model category","NAMO class","Organism","Anatomy","Cell type","Culture system","Modeled mechanism","Publication","Evidence"],"metadata_missing":["Cell source"],"dataset_context":"Available in same 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plus knockdown-with-rescue, giving a variant-level functional readout on subcellular localisation, dendritic growth, spine morphology, migration and axon elongation. This is the closest available assay for classifying MED13L variants of uncertain significance.","notes":null,"context_id":"disorder:MED13L_Syndrome","context_kind":"Disorder","disease_name":"MED13L Syndrome","disease_synonyms":["MED13L haploinsufficiency syndrome","MED13L-related intellectual disability","MRFACD","Mental retardation and distinctive facial features with or without cardiac defects","Asadollahi-Rauch syndrome","Impaired intellectual development and distinctive facial features with or without cardiac defects"],"disease_term":{"id":"MONDO:0014773","label":"cardiac anomalies - developmental delay - facial dysmorphism syndrome","display_label":"MED13L syndrome","url":"http://purl.obolibrary.org/obo/MONDO_0014773"},"experimental_model_type":"OTHER","experimental_model_type_label":"Other","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"},"organism_label":"Mus musculus","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[{"id":"CL:0000540","label":"neuron","display_label":"neuron","url":"http://purl.obolibrary.org/obo/CL_0000540"}],"model_cell_type_labels":["neuron"],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[{"id":"CL:0000540","label":"neuron","display_label":"neuron","url":"http://purl.obolibrary.org/obo/CL_0000540"}],"cell_type_labels":["neuron"],"conditions":[],"cell_source":null,"source_category":null,"culture_system":null,"publication":"PMID:36798993","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36798993","mechanisms":[],"mechanism_names":[],"relationships":[],"fidelities":[],"biological_scales":[],"system_context_sources":["Model-level cell 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influence the dendritic development of cerebral cortical neurons in the mammalian brain.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"Furthermore, we show that mMED13L-knockdown abrogated dendritic growth in vivo, and this effect was significantly rescued by co-electroporation of an RNAi-resistant mMED13L, but weakly by the p.T2162M variant, and not at all by the p.S2163L variant.","explanation":"Demonstrates the rescue-based design that converts the assay into a variant classifier."}],"evidence_text":["Furthermore, we show that mMED13L-knockdown abrogated dendritic growth in vivo, and this effect was significantly rescued by co-electroporation of an RNAi-resistant mMED13L, but weakly by the p.T2162M variant, and not at all by the p.S2163L variant.","Demonstrates the rescue-based design that converts the assay into a variant classifier."],"evidence_status":"Evidence recorded","metadata_completeness":50,"metadata_present":["Model category","Organism","Cell 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disease substitutions, assayed for filament bundling and for actin association, plus imaging of mutant protein in cultured HeLa cells. This is the only system that measures the direction of the biochemical change rather than inferring it from morphology, and it is why this entry curates the lesion as increased rather than decreased actin association.","notes":null,"context_id":"disorder:Platelet-type_Bleeding_Disorder_15","context_kind":"Disorder","disease_name":"Platelet-type Bleeding Disorder 15","disease_synonyms":["BDPLT15","ACTN1-related thrombocytopenia","ACTN1-related macrothrombocytopenia","ACTN1-RT","autosomal dominant macrothrombocytopenia ACTN1-related","bleeding disorder, platelet-type, 15"],"disease_term":{"id":"MONDO:0014078","label":"platelet-type bleeding disorder 15","display_label":"Platelet-type bleeding disorder 15","url":"http://purl.obolibrary.org/obo/MONDO_0014078"},"experimental_model_type":"OTHER","experimental_model_type_label":"Other","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":null,"source_category":null,"culture_system":null,"publication":"PMID:31365757","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/31365757","mechanisms":[{"target":"Increased Alpha-Actinin-1 Actin Cross-Linking Activity","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Platelet-type_Bleeding_Disorder_15.html#pathophysiology-increased-alpha-actinin-1-actin-cross-linking-activity","relationship":"MEASURES","relationship_label":"Measures","fidelity":"MODERATE","fidelity_label":"Moderate","description":"Quantifies filament bundling by nine calmodulin-like and rod-domain mutants and the cytoskeletal association of mutant protein in cells.","limitations":"A cell-free system with purified protein and F-actin, so it reports the intrinsic property of the mutant protein rather than its behaviour in a megakaryocyte, where actin dynamics are shaped by many competing cross-linkers and by calcium signalling. The cellular arm uses HeLa cells, which are as remote from megakaryocytes as Chinese hamster ovary cells are.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0051764","label":"actin crosslink formation","display_label":"actin crosslink formation","url":"http://purl.obolibrary.org/obo/GO_0051764"},{"id":"GO:0051017","label":"actin filament bundle assembly","display_label":"actin filament bundle assembly","url":"http://purl.obolibrary.org/obo/GO_0051017"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Actin filament bundling activity","description":null,"target":"Increased Alpha-Actinin-1 Actin Cross-Linking Activity","direction":"INCREASED","interpretation":"Disease alleles bundle actin filaments more effectively than wild-type protein.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:31365757","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/31365757","reference_title":"Investigation of calmodulin-like and rod domain mutations suggests common molecular mechanism for α-actinin-1-linked congenital macrothrombocytopenia.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"In this study, we examined nine CMTP-causing mutations in the calmodulin-like and rod domains of actinin-1. These mutations increase, to varying degrees, actinin's ability to bundle actin filaments in vitro.","explanation":"The bundling measurement itself, across nine disease alleles."}],"notes":null},{"name":"Cytoskeletal association of mutant actinin in cells","description":null,"target":"Increased Alpha-Actinin-1 Actin Cross-Linking Activity","direction":"INCREASED","interpretation":"Two mutants show increased association with the cellular cytoskeleton, extending the cell-free result into cells.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:31365757","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/31365757","reference_title":"Investigation of calmodulin-like and rod domain mutations suggests common molecular mechanism for α-actinin-1-linked congenital macrothrombocytopenia.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The G764S and E769K mutations increase cytoskeletal association of actinin in cells, and all mutant proteins colocalize with F-actin in cultured HeLa cells.","explanation":"Names the two alleles for which the increase was demonstrated in cells; the remaining seven were shown only to colocalise with F-actin."}],"notes":null}],"evidence":[{"reference":"PMID:31365757","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/31365757","reference_title":"Investigation of calmodulin-like and rod domain mutations suggests common molecular mechanism for α-actinin-1-linked congenital macrothrombocytopenia.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Thus, CMTP-causing actinin-1 mutations outside the actin-binding domain also increase actin association, suggesting a common molecular mechanism underlying actinin-1 related CMTP.","explanation":"Establishes the assay as informative for the cross-linking node and states the conclusion drawn from it."},{"reference":"PMID:31365757","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/31365757","reference_title":"Investigation of calmodulin-like and rod domain mutations suggests common molecular mechanism for α-actinin-1-linked congenital macrothrombocytopenia.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"In this study, we examined nine CMTP-causing mutations in the calmodulin-like and rod domains of actinin-1. These mutations increase, to varying degrees, actinin's ability to bundle actin filaments in vitro.","explanation":"The bundling measurement itself, across nine disease alleles."},{"reference":"PMID:31365757","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/31365757","reference_title":"Investigation of calmodulin-like and rod domain mutations suggests common molecular mechanism for α-actinin-1-linked congenital macrothrombocytopenia.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The G764S and E769K mutations increase cytoskeletal association of actinin in cells, and all mutant proteins colocalize with F-actin in cultured HeLa cells.","explanation":"Names the two alleles for which the increase was demonstrated in cells; the remaining seven were shown only to colocalise with F-actin."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Platelet-type_Bleeding_Disorder_15","model_node_id":"model:kb/disorders/Platelet-type_Bleeding_Disorder_15.yaml:In vitro actin bundling assays with recombinant mutant alpha-actinin-1","focus_node_id":"node:disorder%3APlatelet-type_Bleeding_Disorder_15:pathophysiology:Increased%20Alpha-Actinin-1%20Actin%20Cross-Linking%20Activity","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Platelet-type_Bleeding_Disorder_15.html#pathograph","nodes":[{"id":"model:kb/disorders/Platelet-type_Bleeding_Disorder_15.yaml:In vitro actin bundling assays with recombinant mutant alpha-actinin-1","kind":"experimental_model","kind_label":"NAM model","label":"In vitro actin bundling assays with recombinant mutant alpha-actinin-1","description":"Purified recombinant alpha-actinin-1 carrying disease substitutions, assayed for filament bundling and for actin association, plus imaging of mutant protein in cultured HeLa cells. This is the only system that measures the direction of the biochemical change rather than inferring it from morphology, and it is why this entry curates the lesion as increased rather than decreased actin association.","url":"https://dismech.monarchinitiative.org/pages/disorders/Platelet-type_Bleeding_Disorder_15.html#experimental-model-in-vitro-actin-bundling-assays-with-recombinant-mutant-alpha-actinin-1","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APlatelet-type_Bleeding_Disorder_15:pathophysiology:Increased%20Alpha-Actinin-1%20Actin%20Cross-Linking%20Activity","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Increased Alpha-Actinin-1 Actin Cross-Linking Activity","description":"Mutant alpha-actinin-1 binds and bundles actin filaments more avidly than wild type. Nine calmodulin-like and rod-domain mutants were shown to increase filament bundling in vitro to varying degrees, two of them measurably increased the cytoskeletal association of actinin inside cells, and the actin-binding-domain mutants raise affinity for F-actin directly. The authors of that work read the convergence as a common molecular mechanism for ACTN1-linked macrothrombocytopenia, which is why this node sits on the main chain rather than being treated as one of several parallel biochemical consequences.","url":"https://dismech.monarchinitiative.org/pages/disorders/Platelet-type_Bleeding_Disorder_15.html#pathophysiology-increased-alpha-actinin-1-actin-cross-linking-activity","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3APlatelet-type_Bleeding_Disorder_15:pathophysiology:ACTN1%20Missense%20Variant%20Altering%20Alpha-Actinin-1","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"ACTN1 Missense Variant Altering Alpha-Actinin-1","description":"The initiating lesion is a heterozygous germline missense substitution in ACTN1. Alpha-actinin-1 is an actin-crosslinking protein of the spectrin superfamily that organises the cytoskeleton, and it works as an antiparallel dimer whose two actin-binding domains hold neighbouring filaments together. Substitutions in the actin-binding domain, in the spectrin-like rod repeats and in the calmodulin-like domain all cause the same disease, which is the first clue that they share a downstream effect rather than each disabling a separate function.","url":"https://dismech.monarchinitiative.org/pages/disorders/Platelet-type_Bleeding_Disorder_15.html#pathophysiology-actn1-missense-variant-altering-alpha-actinin-1","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3APlatelet-type_Bleeding_Disorder_15:pathophysiology:Disorganized%20Megakaryocyte%20Actin%20Cytoskeleton","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Disorganized Megakaryocyte Actin Cytoskeleton","description":"Expression of a disease-associated ACTN1 allele disorganises the actin cytoskeleton. The finding is unusually well replicated for a rare disorder: it has been reproduced in Chinese hamster ovary cells for actin-binding and calmodulin-domain alleles, in the same system for a rod-domain allele, in COS-7 cells and cultured megakaryocytes for the French p.Arg46Gln allele, and in the expression work accompanying the largest variant series, where the network was disorganised and the fibres themselves were thicker. Thickened fibres are the morphological counterpart of the increased bundling measured biochemically upstream.","url":"https://dismech.monarchinitiative.org/pages/disorders/Platelet-type_Bleeding_Disorder_15.html#pathophysiology-disorganized-megakaryocyte-actin-cytoskeleton","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"}],"edges":[{"id":"model-link:0:model:kb/disorders/Platelet-type_Bleeding_Disorder_15.yaml:In vitro actin bundling assays with recombinant mutant alpha-actinin-1","source_id":"model:kb/disorders/Platelet-type_Bleeding_Disorder_15.yaml:In vitro actin bundling assays with recombinant mutant alpha-actinin-1","target_id":"node:disorder%3APlatelet-type_Bleeding_Disorder_15:pathophysiology:Increased%20Alpha-Actinin-1%20Actin%20Cross-Linking%20Activity","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Measures","directed":false,"relationship":"MEASURES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"Quantifies filament bundling by nine calmodulin-like and rod-domain mutants and the cytoskeletal association of mutant protein in cells.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3APlatelet-type_Bleeding_Disorder_15:0:0","source_id":"node:disorder%3APlatelet-type_Bleeding_Disorder_15:pathophysiology:ACTN1%20Missense%20Variant%20Altering%20Alpha-Actinin-1","target_id":"node:disorder%3APlatelet-type_Bleeding_Disorder_15:pathophysiology:Increased%20Alpha-Actinin-1%20Actin%20Cross-Linking%20Activity","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"The substitution changes the protein's interaction with F-actin. 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These mutations increase, to varying degrees, actinin's ability to bundle actin filaments in vitro.","explanation":"The bundling measurement itself, across nine disease alleles."},{"reference":"PMID:31365757","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/31365757","reference_title":"Investigation of calmodulin-like and rod domain mutations suggests common molecular mechanism for α-actinin-1-linked congenital macrothrombocytopenia.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The G764S and E769K mutations increase cytoskeletal association of actinin in cells, and all mutant proteins colocalize with F-actin in cultured HeLa cells.","explanation":"Names the two alleles for which the increase was demonstrated in cells; the remaining seven were shown only to colocalise with F-actin."}],"evidence_text":["Thus, CMTP-causing actinin-1 mutations outside the actin-binding domain also increase actin association, suggesting a common molecular mechanism underlying actinin-1 related CMTP.","In this study, we examined nine CMTP-causing mutations in the calmodulin-like and rod domains of actinin-1. These mutations increase, to varying degrees, actinin's ability to bundle actin filaments in vitro.","The G764S and E769K mutations increase cytoskeletal association of actinin in cells, and all mutant proteins colocalize with F-actin in cultured HeLa cells.","Establishes the cell-free assay system and the conclusion the authors drew from it.","The bundling measurement itself, across nine disease alleles.","Names the two alleles for which the increase was demonstrated in cells; the remaining seven were shown only to colocalise with F-actin."],"evidence_status":"Evidence recorded","metadata_completeness":40,"metadata_present":["Model category","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Organism","Anatomy","Cell type","Cell source","Culture system"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Platelet-type_Bleeding_Disorder_15.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Platelet-type_Bleeding_Disorder_15.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Platelet-type_Bleeding_Disorder_15.html#experimental-model-in-vitro-actin-bundling-assays-with-recombinant-mutant-alpha-actinin-1","source_anchor":"experimental-model-in-vitro-actin-bundling-assays-with-recombinant-mutant-alpha-actinin-1"},{"id":"model:kb/disorders/Vitamin_D-Dependent_Rickets_Type_2B.yaml:Index-case EBV-transformed B-cell line","name":"Index-case EBV-transformed B-cell line","description":"EBV-transformed B-cell lines from the index patient and a matched control were used for VDRE-binding-protein studies and the GSE22523 calcitriol-response microarray. 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Reduced embryonic Rpl10l expression was not reproduced in the fibroblasts.","url":"https://dismech.monarchinitiative.org/pages/disorders/BRPF1-Related_Intellectual_Disability.html#experimental-model-inducible-brpf1-null-mouse-embryonic-fibroblasts","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ABRPF1-Related_Intellectual_Disability:pathophysiology:Deficient%20Histone%20H3K23%20Acetylation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Deficient Histone H3K23 Acetylation","description":"Loss of BRPF1 scaffold activity can lower acetylation of histone H3 lysine 23; the effect depends on the allele and experimental context. 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In the hESC knockout study, H3K4me3 persisted and H3K14ac was initially preserved before declining with differentiation; direct H3K4me3 recognition by BRPF1 was not biochemically resolved.","url":"https://dismech.monarchinitiative.org/pages/disorders/BRPF1-Related_Intellectual_Disability.html#pathophysiology-deficient-histone-h3k23-acetylation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ABRPF1-Related_Intellectual_Disability:pathophysiology:Altered%20Chromatin%20Accessibility","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Altered Chromatin Accessibility","description":"Complete BRPF1 deletion in human H1 embryonic stem cells reduces ATAC-seq accessibility at stemness genes while increasing accessibility at lineage-associated genes. 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In mouse hippocampal CA1 tissue, postnatal excitatory-neuron deletion both downregulates selected neural genes and derepresses normally suppressed transcription factors. These are distinct experimental systems; their transcriptomic changes do not identify a universal mediator of the human multisystem phenotype. In zebrafish mutants, anterior Hox expression is initiated normally but subsequently lost in cranial neural crest; this contrasts with elevated Hox expression after mouse forebrain deletion and illustrates tissue-dependent directionality.","url":"https://dismech.monarchinitiative.org/pages/disorders/BRPF1-Related_Intellectual_Disability.html#pathophysiology-altered-developmental-transcriptional-programs","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ABRPF1-Related_Intellectual_Disability:pathophysiology:Aberrant%20Cortical%20Neurogenesis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Aberrant Cortical Neurogenesis","description":"Early forebrain-specific Brpf1 homozygous deletion reduces Tbr2-positive intermediate neuronal progenitors and alters cortical neurogenesis in mice. Developmental transcript changes accompany these abnormalities, but specific transcriptional mediators have not been isolated by rescue. The severe conditional-null model is not equivalent to heterozygous human disease.","url":"https://dismech.monarchinitiative.org/pages/disorders/BRPF1-Related_Intellectual_Disability.html#pathophysiology-aberrant-cortical-neurogenesis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ABRPF1-Related_Intellectual_Disability:pathophysiology:Abnormal%20Corpus%20Callosum%20Development","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Abnormal Corpus Callosum Development","description":"Conditional homozygous Brpf1 loss in the embryonic forebrain produces partial callosal agenesis in mice. Conditional heterozygotes in a separate study have a modest reduction in callosal thickness. These zygosity-dependent anatomical changes provide model evidence, while the route to rare human agenesis or hypoplasia remains unproven.","url":"https://dismech.monarchinitiative.org/pages/disorders/BRPF1-Related_Intellectual_Disability.html#pathophysiology-abnormal-corpus-callosum-development","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ABRPF1-Related_Intellectual_Disability:pathophysiology:Altered%20Chromatin%20Accessibility","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Altered Chromatin Accessibility","description":"Complete BRPF1 deletion in human H1 embryonic stem cells reduces ATAC-seq accessibility at stemness genes while increasing accessibility at lineage-associated genes. 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Reported anomalies include patent ductus arteriosus and atrial or ventricular septal defects.","url":"https://dismech.monarchinitiative.org/pages/disorders/BRPF1-Related_Intellectual_Disability.html#phenotype-congenital-cardiac-anomalies","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ABRPF1-Related_Intellectual_Disability:pathophysiology:Deficient%20Histone%20H3K23%20Propionylation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Deficient Histone H3K23 Propionylation","description":"BRPF1-KAT6 complexes propionylate H3K23. Several patient variants impair this activity, and the mark is reduced in Pro370Ser lymphoblastoid cells and Arg455Ter lymphoblastoid cells and fibroblasts. Complete Brpf1 deletion abolishes detectable H3K23 propionylation in mouse embryos and cultured fibroblasts. Effects are allele- and assay-dependent: Pro76Leu retained stimulation in the biochemical assay, and some truncating products also retained activity. The independent contribution of propionylation loss to the human phenotype is unresolved.","url":"https://dismech.monarchinitiative.org/pages/disorders/BRPF1-Related_Intellectual_Disability.html#pathophysiology-deficient-histone-h3k23-propionylation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ABRPF1-Related_Intellectual_Disability:pathophysiology:Deregulated%20Ocular%20and%20Periocular%20Developmental%20Transcription%20Factor%20Programs","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Deregulated Ocular and Periocular Developmental Transcription Factor Programs","description":"BRPF1-dependent regulation of Pitx2, Hmx1 and Pax6 has been proposed as a route to the ocular and periocular phenotype. The cited clinical cohort extrapolates from developmental-model literature; it does not directly test these transcription factors in human periocular tissue. The connection to ptosis, blepharophimosis and ocular alignment remains hypothetical.","url":"https://dismech.monarchinitiative.org/pages/disorders/BRPF1-Related_Intellectual_Disability.html#pathophysiology-deregulated-ocular-and-periocular-developmental-transcription-factor-programs","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"HYPOTHETICAL","mechanism_confidence_label":"Hypothetical"},{"id":"node:disorder%3ABRPF1-Related_Intellectual_Disability:phenotype:Global%20Developmental%20Delay","kind":"phenotype","kind_label":"Phenotype","label":"Global Developmental Delay","description":"Global developmental delay affecting motor, language and adaptive domains is the presenting feature in most reported individuals, and was the reason for ascertainment in the founding series.","url":"https://dismech.monarchinitiative.org/pages/disorders/BRPF1-Related_Intellectual_Disability.html#phenotype-global-developmental-delay","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ABRPF1-Related_Intellectual_Disability:pathophysiology:Impaired%20Axonal%20Outgrowth","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Axonal Outgrowth","description":"Primary cortical neurons from E16.5 Emx1-lineage Brpf1 conditional heterozygotes have shorter Tau-positive axons at DIV5; conditional homozygous deletion produces a larger reduction. 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These observations concern mouse neurons; they do not establish a human neuronal phenotype or a transcriptional mediator.","url":"https://dismech.monarchinitiative.org/pages/disorders/BRPF1-Related_Intellectual_Disability.html#pathophysiology-impaired-dendritic-arborization","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ABRPF1-Related_Intellectual_Disability:pathophysiology:Impaired%20Hematopoietic%20Stem%20and%20Progenitor%20Cell%20Maintenance","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Hematopoietic Stem and Progenitor Cell Maintenance","description":"Hematopoietic Vav1-iCre Brpf1 homozygous deletion impairs fetal stem/progenitor function and causes progressive postnatal marrow failure in mice. The phenotype includes loss of repopulating capacity despite preserved marrow homing, reduced neonatal LSK proliferation, and increased apoptosis, oxidative stress and senescence. Fetal LSK proliferation is initially preserved. Conditional heterozygotes have unchanged survival and neonatal LSK-cell numbers in the reported tests. 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A transient form associated with ongoing inflammation resolves with anti-inflammatory therapy, so the choice between drugs and pericardiectomy turns on distinguishing active inflammation from established fibrosis.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Pericarditis.html#pathophysiology-constrictive-physiology","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:1:model:kb/disorders/Pericarditis.yaml:Interferon-gamma knockout mouse constrictive pericarditis model","source_id":"model:kb/disorders/Pericarditis.yaml:Interferon-gamma knockout mouse constrictive pericarditis model","target_id":"node:disorder%3APericarditis:pathophysiology:Fibrotic%20organization%20of%20the%20pericardium","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[1]","label":"Not Specified","directed":false,"relationship":"NOT_SPECIFIED","fidelity":"NOT_SPECIFIED","causal_link_type":null,"causal_link_type_label":null,"description":"Pericardial inflammation and fibrosis are the lesion that produces the phenotype in this model.\n","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3APericarditis:3:1","source_id":"node:disorder%3APericarditis:pathophysiology:Acute%20pericardial%20inflammatory%20exudate","target_id":"node:disorder%3APericarditis:pathophysiology:Fibrotic%20organization%20of%20the%20pericardium","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[3].downstream[1]","label":"Indirectly causes (known intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_KNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Known Intermediates","description":"Persistent or severe inflammation may organise rather than resolve, with the probability depending strongly on the aetiology rather than on the acute severity.\n","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3APericarditis:7:0","source_id":"node:disorder%3APericarditis:pathophysiology:Fibrotic%20organization%20of%20the%20pericardium","target_id":"node:disorder%3APericarditis:pathophysiology:Constrictive%20physiology","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[7].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"A non-compliant pericardial shell sets a fixed limit on total cardiac volume.\n","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0}]}}],"mechanism_names":["Constrictive physiology","Fibrotic organization of the pericardium"],"relationships":["Not Specified"],"fidelities":["Not Specified"],"biological_scales":["Organism","Tissue"],"system_context_sources":["Linked mechanism anatomy","Linked mechanism cell type","Linked mechanism biological scale"],"modeled_system_labels":["pericardium","fibroblast","Organism","Tissue"],"biological_process_terms":[],"biological_processes":[],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":[],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:15505106","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/15505106","reference_title":"Novel model of constrictive pericarditis associated with autoimmune heart disease in interferon-gamma-knockout mice.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"Constrictive pericarditis represents a serious hemodynamic syndrome that may lead to heart failure. Studies of its pathophysiological mechanisms have been impeded by the lack of an animal model.","explanation":"States the gap this model was built to fill, which is also the reason mechanistic understanding of constriction lags behind that of the acute disease."},{"reference":"PMID:15505106","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/15505106","reference_title":"Novel model of constrictive pericarditis associated with autoimmune heart disease in interferon-gamma-knockout mice.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"This phenotype was not associated with the severity of myocarditis but correlated with the presence of grossly detectable adhesive pericarditis present only in the KO group and characterized by increased pericardial inflammation and fibrosis.","explanation":"The dissociation from myocarditis severity, which is what makes the model informative about pericardial rather than myocardial mechanism."}],"evidence_text":["Constrictive pericarditis represents a serious hemodynamic syndrome that may lead to heart failure. Studies of its pathophysiological mechanisms have been impeded by the lack of an animal model.","This phenotype was not associated with the severity of myocarditis but correlated with the presence of grossly detectable adhesive pericarditis present only in the KO group and characterized by increased pericardial inflammation and fibrosis.","States the gap this model was built to fill, which is also the reason mechanistic understanding of constriction lags behind that of the acute disease.","The dissociation from myocarditis severity, which is what makes the model informative about pericardial rather than myocardial mechanism."],"evidence_status":"Evidence recorded","metadata_completeness":70,"metadata_present":["Model category","Organism","Anatomy","Cell type","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Cell source","Culture system"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Pericarditis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pericarditis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pericarditis.html#experimental-model-interferon-gamma-knockout-mouse-constrictive-pericarditis-model","source_anchor":"experimental-model-interferon-gamma-knockout-mouse-constrictive-pericarditis-model"},{"id":"model:kb/disorders/Autosomal_Dominant_Cutis_Laxa_1.yaml:Intragenic ELN duplication family fibroblasts","name":"Intragenic ELN duplication family fibroblasts","description":"Metabolic labeling and immunoprecipitation identified normal68 kDa tropoelastin plus an abnormal120 kDa protein. Mutant protein was partly secreted and partly retained, with both intracellular and matrix immunostaining.","notes":"The regenerated reference provides the abstract only; complete methods, sample-replication details and quantitative secretion fractions were unavailable. These findings do not prove which retained or matrix protein fraction causes severe lung disease.","context_id":"disorder:Autosomal_Dominant_Cutis_Laxa_1","context_kind":"Disorder","disease_name":"Autosomal Dominant Cutis Laxa 1","disease_synonyms":["ADCL1","ELN-related cutis laxa","ELN autosomal dominant cutis laxa","Cutis laxa, autosomal dominant type 1","Autosomal dominant cutis laxa caused by mutation in ELN","Cutis laxa, autosomal dominant"],"disease_term":{"id":"MONDO:0007411","label":"cutis laxa, autosomal dominant 1","display_label":"Autosomal Dominant Cutis Laxa 1","url":"http://purl.obolibrary.org/obo/MONDO_0007411"},"experimental_model_type":"PRIMARY_CELL_CULTURE","experimental_model_type_label":"Primary-cell culture","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[{"id":"CL:0002620","label":"skin fibroblast","display_label":"skin fibroblast","url":"http://purl.obolibrary.org/obo/CL_0002620"}],"model_cell_type_labels":["skin fibroblast"],"linked_cell_types":[{"id":"CL:0002620","label":"skin fibroblast","display_label":"skin fibroblast","url":"http://purl.obolibrary.org/obo/CL_0002620"}],"linked_cell_type_labels":["skin fibroblast"],"cell_types":[{"id":"CL:0002620","label":"skin fibroblast","display_label":"skin fibroblast","url":"http://purl.obolibrary.org/obo/CL_0002620"}],"cell_type_labels":["skin fibroblast"],"conditions":[],"cell_source":"Dermal fibroblasts from the proband and affected daughter","source_category":"Primary / biopsy-derived","culture_system":null,"publication":"PMID:15955094","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/15955094","mechanisms":[{"target":"Intracellular Mutant Tropoelastin Retention","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Dominant_Cutis_Laxa_1.html#pathophysiology-intracellular-mutant-tropoelastin-retention","relationship":"PARTIALLY_RECAPITULATES","relationship_label":"Partially Recapitulates","fidelity":"MODERATE","fidelity_label":"Moderate","description":"Mutant-specific immunostaining and immunoprecipitation support intracellular retention alongside secretion.","limitations":"Abstract-only available source; no intervention resolves the contribution to clinical injury.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[{"id":"CL:0002620","label":"skin fibroblast","display_label":"skin fibroblast","url":"http://purl.obolibrary.org/obo/CL_0002620"}],"biological_processes":[],"pathways":[],"genes":[],"chemicals":[],"readouts":[],"evidence":[{"reference":"PMID:15955094","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/15955094","reference_title":"Autosomal dominant cutis laxa with severe lung disease: synthesis and matrix deposition of mutant tropoelastin.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"A polyclonal antibody raised against a unique peptide in the mutant TE molecule showed both intracellular and matrix staining.","explanation":"The mutant-specific antibody detects both compartments."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Autosomal_Dominant_Cutis_Laxa_1","model_node_id":"model:kb/disorders/Autosomal_Dominant_Cutis_Laxa_1.yaml:Intragenic ELN duplication family fibroblasts","focus_node_id":"node:disorder%3AAutosomal_Dominant_Cutis_Laxa_1:pathophysiology:Intracellular%20Mutant%20Tropoelastin%20Retention","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Dominant_Cutis_Laxa_1.html#pathograph","nodes":[{"id":"model:kb/disorders/Autosomal_Dominant_Cutis_Laxa_1.yaml:Intragenic ELN duplication family fibroblasts","kind":"experimental_model","kind_label":"NAM model","label":"Intragenic ELN duplication family fibroblasts","description":"Metabolic labeling and immunoprecipitation identified normal68 kDa tropoelastin plus an abnormal120 kDa protein. Mutant protein was partly secreted and partly retained, with both intracellular and matrix immunostaining.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Dominant_Cutis_Laxa_1.html#experimental-model-intragenic-eln-duplication-family-fibroblasts","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAutosomal_Dominant_Cutis_Laxa_1:pathophysiology:Intracellular%20Mutant%20Tropoelastin%20Retention","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Intracellular Mutant Tropoelastin Retention","description":"Some abnormal tropoelastin remains intracellular while another fraction is secreted. This has been demonstrated in the duplication-family fibroblasts and selected frameshift cultures or transgenic lung. Retention is not assumed universal or complete.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Dominant_Cutis_Laxa_1.html#pathophysiology-intracellular-mutant-tropoelastin-retention","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAutosomal_Dominant_Cutis_Laxa_1:pathophysiology:C-Terminally%20Altered%20Tropoelastin","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"C-Terminally Altered Tropoelastin","description":"Affected alleles can produce tropoelastin with a replaced and often extended carboxy terminus. Protein is demonstrable in selected patient cultures, but transcript abundance, exon skipping and partial nonsense-mediated decay depend on allele and isoform. Splicing can produce truncated, extended or mutation-skipping products; universal escape from RNA decay is not established.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Dominant_Cutis_Laxa_1.html#pathophysiology-c-terminally-altered-tropoelastin","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAutosomal_Dominant_Cutis_Laxa_1:pathophysiology:Endoplasmic%20Reticulum%20Stress%20Response","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Endoplasmic Reticulum Stress Response","description":"Selected patient fibroblasts show elevated BiP or phosphorylated eIF2alpha, with different results by cell line. The exon-30 line CL-3 has the clearest combined stress readout; CL-1 lacks a significant BiP increase. Transgenic lung also shows increased phosphorylated eIF2alpha. These assays do not establish a required serial pathway to organ disease.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Dominant_Cutis_Laxa_1.html#pathophysiology-endoplasmic-reticulum-stress-response","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Autosomal_Dominant_Cutis_Laxa_1.yaml:Intragenic ELN duplication family fibroblasts","source_id":"model:kb/disorders/Autosomal_Dominant_Cutis_Laxa_1.yaml:Intragenic ELN duplication family fibroblasts","target_id":"node:disorder%3AAutosomal_Dominant_Cutis_Laxa_1:pathophysiology:Intracellular%20Mutant%20Tropoelastin%20Retention","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Partially Recapitulates","directed":false,"relationship":"PARTIALLY_RECAPITULATES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"Mutant-specific immunostaining and immunoprecipitation support intracellular retention alongside secretion.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AAutosomal_Dominant_Cutis_Laxa_1:1:3","source_id":"node:disorder%3AAutosomal_Dominant_Cutis_Laxa_1:pathophysiology:C-Terminally%20Altered%20Tropoelastin","target_id":"node:disorder%3AAutosomal_Dominant_Cutis_Laxa_1:pathophysiology:Intracellular%20Mutant%20Tropoelastin%20Retention","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[3]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"The tested abnormal proteins show incomplete secretion with intracellular retention; other alleles need not share the same degree.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AAutosomal_Dominant_Cutis_Laxa_1:8:0","source_id":"node:disorder%3AAutosomal_Dominant_Cutis_Laxa_1:pathophysiology:Intracellular%20Mutant%20Tropoelastin%20Retention","target_id":"node:disorder%3AAutosomal_Dominant_Cutis_Laxa_1:pathophysiology:Endoplasmic%20Reticulum%20Stress%20Response","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[8].downstream[0]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"Colocalization of retained tropoelastin with stress markers supports the proposed trigger, without selective removal of retention or proof of necessity.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1}]}}],"mechanism_names":["Intracellular Mutant Tropoelastin Retention"],"relationships":["Partially Recapitulates"],"fidelities":["Moderate"],"biological_scales":["Cellular"],"system_context_sources":["Model-level cell type","Linked mechanism cell type","Linked mechanism biological scale"],"modeled_system_labels":["skin fibroblast","Cellular"],"biological_process_terms":[],"biological_processes":[],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":[],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:15955094","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/15955094","reference_title":"Autosomal dominant cutis laxa with severe lung disease: synthesis and matrix deposition of mutant tropoelastin.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Immunoprecipitation experiments showed that the mutant TE was partially secreted and partially retained intracellularly.","explanation":"The abstract directly describes mixed secretion and retention."},{"reference":"PMID:15955094","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/15955094","reference_title":"Autosomal dominant cutis laxa with severe lung disease: synthesis and matrix deposition of mutant tropoelastin.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"A polyclonal antibody raised against a unique peptide in the mutant TE molecule showed both intracellular and matrix staining.","explanation":"The mutant-specific antibody detects both compartments."}],"evidence_text":["Immunoprecipitation experiments showed that the mutant TE was partially secreted and partially retained intracellularly.","A polyclonal antibody raised against a unique peptide in the mutant TE molecule showed both intracellular and matrix staining.","The abstract directly describes mixed secretion and retention.","The mutant-specific antibody detects both compartments."],"evidence_status":"Evidence recorded","metadata_completeness":60,"metadata_present":["Model category","Cell type","Cell source","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Organism","Anatomy","Culture system"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Autosomal_Dominant_Cutis_Laxa_1.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autosomal_Dominant_Cutis_Laxa_1.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Dominant_Cutis_Laxa_1.html#experimental-model-intragenic-eln-duplication-family-fibroblasts","source_anchor":"experimental-model-intragenic-eln-duplication-family-fibroblasts"},{"id":"model:kb/disorders/Behr_Syndrome.yaml:iPS-OPA1-BEHR","name":"iPS-OPA1-BEHR","description":"The transgene-free iPS-OPA1-BEHR line was generated from a 48-year-old patient with c.610+364G>A and c.1311A>G. The report establishes retained variants, pluripotency and three-germ-layer differentiation. It provides a model resource; it does not demonstrate retinal-neuron phenotypes or therapeutic rescue.","notes":null,"context_id":"disorder:Behr_Syndrome","context_kind":"Disorder","disease_name":"Behr Syndrome","disease_synonyms":["BEHRS","OPA1-related Behr syndrome","optic atrophy, infantile hereditary, Behr complicated form of","optic atrophy in early childhood, associated with ataxia, spasticity, intellectual disability, and posterior column sensory loss"],"disease_term":{"id":"MONDO:0008858","label":"Behr syndrome","display_label":"Behr syndrome","url":"http://purl.obolibrary.org/obo/MONDO_0008858"},"experimental_model_type":"IPSC_DERIVED_MODEL","experimental_model_type_label":"iPSC-derived model","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},"organism_label":"Homo sapiens","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":"Human skin fibroblasts from a Behr syndrome patient with compound heterozygous OPA1 mutations","source_category":"Patient-derived","culture_system":null,"publication":"PMID:27879217","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/27879217","mechanisms":[],"mechanism_names":[],"relationships":[],"fidelities":[],"biological_scales":[],"system_context_sources":[],"modeled_system_labels":[],"biological_process_terms":[],"biological_processes":[],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":[],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:27879217","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/27879217","reference_title":"Generation of optic atrophy 1 patient-derived induced pluripotent stem cells (iPS-OPA1-BEHR) for disease modeling of complex optic atrophy syndromes (Behr syndrome).","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Human skin fibroblasts were isolated from a 48-year-old patient carrying compound heterozygous mutations (c.610+364G>A and c.1311A>G) in OPA1, responsible for early onset optic atrophy complicated by ataxia and pyramidal signs (Behr syndrome; OMIM #210000).","explanation":"Documents the derivation of a Behr-syndrome patient iPSC line from compound heterozygous OPA1 fibroblasts, and independently confirms the compound heterozygous OPA1 genotype with the ataxia/pyramidal-sign phenotype.\n"}],"evidence_text":["Human skin fibroblasts were isolated from a 48-year-old patient carrying compound heterozygous mutations (c.610+364G>A and c.1311A>G) in OPA1, responsible for early onset optic atrophy complicated by ataxia and pyramidal signs (Behr syndrome; OMIM #210000).","Documents the derivation of a Behr-syndrome patient iPSC line from compound heterozygous OPA1 fibroblasts, and independently confirms the compound heterozygous OPA1 genotype with the ataxia/pyramidal-sign phenotype."],"evidence_status":"Evidence recorded","metadata_completeness":50,"metadata_present":["Model category","Organism","Cell source","Publication","Evidence"],"metadata_missing":["NAMO class","Anatomy","Cell type","Culture system","Modeled mechanism"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Behr_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Behr_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Behr_Syndrome.html#experimental-model-ips-opa1-behr","source_anchor":"experimental-model-ips-opa1-behr"},{"id":"model:kb/disorders/Hypochondrogenesis.yaml:iPSC-Derived Chondrocyte Model","name":"iPSC-Derived Chondrocyte Model","description":"Human iPSC-derived skeletal development platform that directs sclerotome to chondrocytes and osteoblasts, recapitulating endochondral bone formation. 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later organoid experiments use a different model and assay."},{"reference":"PMID:36321451","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/36321451","reference_title":"Pathogenesis of Cardiomyopathy Caused by Variants in ALPK3, an Essential Pseudokinase in the Cardiomyocyte Nucleus and Sarcomere.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Loss of ALPK3 causes mislocalization of myomesins, critical force-buffering proteins in cardiomyocytes, and also dysregulates M-band proteins necessary for sarcomere protein turnover.","explanation":"Supports treating this model as informative for the myomesin mislocalization node."},{"reference":"PMID:36321451","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/36321451","reference_title":"Pathogenesis of Cardiomyopathy Caused by Variants in ALPK3, an Essential Pseudokinase in the Cardiomyocyte Nucleus and Sarcomere.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"ALPK3 loss-of-function variants caused myomesin proteins to mislocalize and also dysregulated several additional M-band proteins involved in sarcomere protein turnover, which ultimately impaired cardiomyocyte structure and function.","explanation":"Reports the localization measurement behind this readout."}],"evidence_text":["We explored the putative kinase activity of ALPK3 and the consequences of damaging variants using isogenic human induced pluripotent stem cell-derived cardiomyocytes, mice, and human patient tissues.","ALPK3del/del hiPSC-CMs had reduced ALPK3 protein expression (~39% WT), indicating that these cells produce a truncated ALPK3 protein with reduced stability","did not detect significant differences between WT, ALPK3ins/del, and ALPK3dIC/dIC hiPSC-CMs","Loss of ALPK3 causes mislocalization of myomesins, critical force-buffering proteins in cardiomyocytes, and also dysregulates M-band proteins necessary for sarcomere protein turnover.","ALPK3 loss-of-function variants caused myomesin proteins to mislocalize and also dysregulated several additional M-band proteins involved in sarcomere protein turnover, which ultimately impaired cardiomyocyte structure and function.","Describes the isogenic iPSC-cardiomyocyte system used here.","Direct evidence that engineered truncations are not equivalent to complete protein absence.","SarcTrack analysis of more than 40,000 sarcomeres per line found no significant contractility difference; 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The cellular assay supports increased oxidative stress without identifying a specific reactive species."},{"reference":"url:https://oup.silverchair-cdn.com/article-minimal/6650380","reference_url":null,"reference_title":"https://oup.silverchair-cdn.com/article-minimal/6650380","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"we observed a progressive degeneration of neuronal processes ... which began with the formation of small clusters of shrinking neuronal cells ... between Days 17 and 19 post-ND in five independent cultures","explanation":"Publisher full text of Pavinato et al., Brain 2023, PMID:35979925: CAPRIN1 haploinsufficiency causes a neurodevelopmental disorder with language impairment, ADHD and ASD. 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The mutant procollagen was not recognized by the ER proteostasis network and the unfolded protein response was not activated, demonstrating a failure in cellular surveillance that allows secretion of defective collagen and pathogenic matrix deposition.\n","notes":null,"context_id":"disorder:Spondyloepimetaphyseal_Dysplasia_Strudwick_Type","context_kind":"Disorder","disease_name":"Spondyloepimetaphyseal Dysplasia Strudwick Type","disease_synonyms":[],"disease_term":{"id":"MONDO:0008476","label":"spondyloepimetaphyseal dysplasia, Strudwick type","display_label":"spondyloepimetaphyseal dysplasia Strudwick type","url":"http://purl.obolibrary.org/obo/MONDO_0008476"},"experimental_model_type":"IPSC_DERIVED_MODEL","experimental_model_type_label":"iPSC-derived model","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},"organism_label":"Homo sapiens","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[{"id":"CL:0000138","label":"chondrocyte","display_label":"Chondrocyte","url":"http://purl.obolibrary.org/obo/CL_0000138"}],"model_cell_type_labels":["chondrocyte"],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[{"id":"CL:0000138","label":"chondrocyte","display_label":"Chondrocyte","url":"http://purl.obolibrary.org/obo/CL_0000138"}],"cell_type_labels":["chondrocyte"],"conditions":[],"cell_source":null,"source_category":"iPSC-derived","culture_system":null,"publication":"PMID:40602718","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40602718","mechanisms":[],"mechanism_names":[],"relationships":[],"fidelities":[],"biological_scales":[],"system_context_sources":["Model-level cell type"],"modeled_system_labels":["chondrocyte"],"biological_process_terms":[],"biological_processes":[],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":[],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[],"evidence_text":[],"evidence_status":"No evidence block recorded","metadata_completeness":40,"metadata_present":["Model category","Organism","Cell type","Publication"],"metadata_missing":["NAMO class","Anatomy","Cell source","Culture system","Modeled mechanism","Evidence"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Spondyloepimetaphyseal_Dysplasia_Strudwick_Type.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Spondyloepimetaphyseal_Dysplasia_Strudwick_Type.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Spondyloepimetaphyseal_Dysplasia_Strudwick_Type.html#experimental-model-isogenic-col2a1-arg719cys-ipsc-derived-cartilage","source_anchor":"experimental-model-isogenic-col2a1-arg719cys-ipsc-derived-cartilage"},{"id":"model:kb/disorders/Hypertrophic_Cardiomyopathy_26.yaml:Isogenic CRISPR FLNC hiPSC-cardiomyocyte series","name":"Isogenic CRISPR FLNC hiPSC-cardiomyocyte series","description":"Human induced pluripotent stem cell-derived cardiomyocytes CRISPR-edited to a matched allelic series: wild type, FLNC null, FLNC haploinsufficient (modelling the truncating/dilated arm), and a heterozygous in-frame deletion that preserves expression but forms aggregates (modelling the non-truncating/hypertrophic arm). The reference human system for separating the contractile from the proteostatic consequences of FLNC variants.","notes":null,"context_id":"disorder:Hypertrophic_Cardiomyopathy_26","context_kind":"Disorder","disease_name":"Hypertrophic Cardiomyopathy 26","disease_synonyms":["CMH26","FLNC hypertrophic cardiomyopathy","cardiomyopathy, familial hypertrophic, 26","hypertrophic cardiomyopathy caused by mutation in FLNC","cardiomyopathy, familial restrictive 5"],"disease_term":{"id":"MONDO:0014883","label":"hypertrophic cardiomyopathy 26","display_label":"hypertrophic cardiomyopathy 26","url":"http://purl.obolibrary.org/obo/MONDO_0014883"},"experimental_model_type":"IPSC_DERIVED_MODEL","experimental_model_type_label":"iPSC-derived model","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},"organism_label":"Homo sapiens","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[{"id":"CL:0000746","label":"cardiac muscle cell","display_label":"Cardiomyocyte","url":"http://purl.obolibrary.org/obo/CL_0000746"}],"model_cell_type_labels":["cardiac muscle cell"],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[{"id":"CL:0000746","label":"cardiac muscle cell","display_label":"Cardiomyocyte","url":"http://purl.obolibrary.org/obo/CL_0000746"}],"cell_type_labels":["cardiac muscle cell"],"conditions":[],"cell_source":"CRISPR/Cas9-edited isogenic human iPSC lines","source_category":"iPSC-derived","culture_system":null,"publication":"PMID:34405687","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34405687","mechanisms":[],"mechanism_names":[],"relationships":[],"fidelities":[],"biological_scales":[],"system_context_sources":["Model-level cell type"],"modeled_system_labels":["cardiac muscle cell"],"biological_process_terms":[],"biological_processes":[],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":[],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"DOI:10.1161/CIRCRESAHA.120.317076","reference_url":null,"reference_title":"Filamin C Cardiomyopathy Variants Cause Protein and Lysosome Accumulation","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"which did not affect FLNC expression but caused aggregate formation, similar to FLNC variants associated with hypertrophic cardiomyopathy.","explanation":"Identifies the in-frame-deletion line as the engineered model of the hypertrophic (aggregate-forming) FLNC variant class."}],"evidence_text":["which did not affect FLNC expression but caused aggregate formation, similar to FLNC variants associated with hypertrophic cardiomyopathy.","Identifies the in-frame-deletion line as the engineered model of the hypertrophic (aggregate-forming) FLNC variant class."],"evidence_status":"Evidence recorded","metadata_completeness":60,"metadata_present":["Model category","Organism","Cell type","Cell source","Publication","Evidence"],"metadata_missing":["NAMO class","Anatomy","Culture system","Modeled mechanism"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Hypertrophic_Cardiomyopathy_26.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hypertrophic_Cardiomyopathy_26.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_26.html#experimental-model-isogenic-crispr-flnc-hipsc-cardiomyocyte-series","source_anchor":"experimental-model-isogenic-crispr-flnc-hipsc-cardiomyocyte-series"},{"id":"model:kb/disorders/Left_Ventricular_Noncompaction_10.yaml:Isogenic hiPSC-cardiomyocytes carrying MYBPC3 premature termination codon variants","name":"Isogenic hiPSC-cardiomyocytes carrying MYBPC3 premature termination codon variants","description":"Isogenic human cardiomyocytes carrying MYBPC3 premature termination codon variants, including p.R943x - the same nonsense change as the c.2827C>T (p.Arg943*) Dutch founder allele that appears homozygously and in compound heterozygosity in the founding LVNC10 case series. The system establishes two things this entry's molecular node asserts: no truncated peptide is produced, and nonsense-mediated decay is chronically engaged. It also supplies a genuine complication, recorded in the discussion below: at the heterozygous dose in this in vitro system, MYBPC3 mRNA fell but cMyBP-C protein did not.","notes":null,"context_id":"disorder:Left_Ventricular_Noncompaction_10","context_kind":"Disorder","disease_name":"Left Ventricular Noncompaction 10","disease_synonyms":["LVNC10","left ventricular noncompaction type 10","MYBPC3 left ventricular noncompaction","left ventricular noncompaction caused by mutation in MYBPC3","cardiomyopathy, dilated, 1MM"],"disease_term":{"id":"MONDO:0014163","label":"left ventricular noncompaction 10","display_label":"left ventricular noncompaction 10","url":"http://purl.obolibrary.org/obo/MONDO_0014163"},"experimental_model_type":"IPSC_DERIVED_MODEL","experimental_model_type_label":"iPSC-derived model","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},"organism_label":"Homo sapiens","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[{"id":"CL:0000746","label":"cardiac muscle cell","display_label":"Cardiomyocyte","url":"http://purl.obolibrary.org/obo/CL_0000746"}],"model_cell_type_labels":["cardiac muscle cell"],"linked_cell_types":[{"id":"CL:0000746","label":"cardiac muscle cell","display_label":"Cardiomyocyte","url":"http://purl.obolibrary.org/obo/CL_0000746"}],"linked_cell_type_labels":["cardiac muscle cell"],"cell_types":[{"id":"CL:0000746","label":"cardiac muscle cell","display_label":"Cardiomyocyte","url":"http://purl.obolibrary.org/obo/CL_0000746"}],"cell_type_labels":["cardiac muscle cell"],"conditions":[],"cell_source":"Genome-edited isogenic iPSC lines from hypertrophic cardiomyopathy patients carrying MYBPC3 p.R943x and p.R1073P_Fsx4","source_category":"Patient-derived","culture_system":null,"publication":"PMID:30586709","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/30586709","mechanisms":[{"target":"MYBPC3 Loss-of-Function Variant and cMyBP-C Depletion","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Left_Ventricular_Noncompaction_10.html#pathophysiology-mybpc3-loss-of-function-variant-and-cmybp-c-depletion","relationship":"PARTIALLY_RECAPITULATES","relationship_label":"Partially Recapitulates","fidelity":"MODERATE","fidelity_label":"Moderate","description":"Establishes the transcript-level fate of MYBPC3 premature termination codon alleles in human cardiomyocytes: no truncated peptide, and chronic nonsense-mediated decay activation.","limitations":"The lines are heterozygous, the CMH4 allelic regime, not the biallelic regime that defines LVNC10, so the dose state this node turns on is not the one modeled. More pointedly, protein levels were comparable to isogenic controls despite reduced mRNA, which the authors read as haploinsufficiency not contributing in vitro. That does not overturn the ~20% residual protein measured in affected human cardiac tissue in a compound heterozygous LVNC case, but it does mean this model supports the transcript arm of the node and not the protein-depletion arm.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[{"id":"CL:0000746","label":"cardiac muscle cell","display_label":"Cardiomyocyte","url":"http://purl.obolibrary.org/obo/CL_0000746"}],"biological_processes":[{"id":"GO:0045214","label":"sarcomere organization","display_label":"Sarcomere Organization","url":"http://purl.obolibrary.org/obo/GO_0045214"}],"pathways":[],"genes":[{"id":"hgnc:7551","label":"MYBPC3","display_label":"MYBPC3","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/7551"}],"chemicals":[],"readouts":[{"name":"Nonsense-mediated decay pathway activity","description":"Transcriptome-level assessment of nonsense-mediated decay activation in MYBPC3 premature-termination-codon cardiomyocytes against isogenic controls.","target":"MYBPC3 Loss-of-Function Variant and cMyBP-C Depletion","direction":"INCREASED","interpretation":"Chronic nonsense-mediated decay engagement is the transcript-level mechanism by which these alleles fail to yield functional protein.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:30586709","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30586709","reference_title":"A Premature Termination Codon Mutation in MYBPC3 Causes Hypertrophic Cardiomyopathy via Chronic Activation of Nonsense-Mediated Decay.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"At the molecular level, the nonsense-mediated decay pathway was activated, and a set of genes involved in major cardiac signaling pathways was dysregulated in HCM iPSC-CMs, indicating an HCM gene signature in vitro.","explanation":"Reports the measured activation of the pathway and its direction."}],"notes":null}],"evidence":[{"reference":"PMID:30586709","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30586709","reference_title":"A Premature Termination Codon Mutation in MYBPC3 Causes Hypertrophic Cardiomyopathy via Chronic Activation of Nonsense-Mediated Decay.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The mRNA expression levels of MYBPC3 were significantly reduced in mutant iPSC-CMs, but the protein levels were comparable among isogenic iPSC-CMs, suggesting that haploinsufficiency of MYBPC3 does not contribute to the pathogenesis of HCM in vitro.","explanation":"Carries both halves of what this link claims: the transcript falls, and the protein does not follow. That split is why the link is PARTIALLY_RECAPITULATES and why the divergences above are recorded."},{"reference":"PMID:30586709","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30586709","reference_title":"A Premature Termination Codon Mutation in MYBPC3 Causes Hypertrophic Cardiomyopathy via Chronic Activation of Nonsense-Mediated Decay.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"At the molecular level, the nonsense-mediated decay pathway was activated, and a set of genes involved in major cardiac signaling pathways was dysregulated in HCM iPSC-CMs, indicating an HCM gene signature in vitro.","explanation":"Reports the measured activation of the pathway and its direction."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Left_Ventricular_Noncompaction_10","model_node_id":"model:kb/disorders/Left_Ventricular_Noncompaction_10.yaml:Isogenic hiPSC-cardiomyocytes carrying MYBPC3 premature termination codon variants","focus_node_id":"node:disorder%3ALeft_Ventricular_Noncompaction_10:pathophysiology:MYBPC3%20Loss-of-Function%20Variant%20and%20cMyBP-C%20Depletion","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Left_Ventricular_Noncompaction_10.html#pathograph","nodes":[{"id":"model:kb/disorders/Left_Ventricular_Noncompaction_10.yaml:Isogenic hiPSC-cardiomyocytes carrying MYBPC3 premature termination codon variants","kind":"experimental_model","kind_label":"NAM model","label":"Isogenic hiPSC-cardiomyocytes carrying MYBPC3 premature termination codon variants","description":"Isogenic human cardiomyocytes carrying MYBPC3 premature termination codon variants, including p.R943x - the same nonsense change as the c.2827C>T (p.Arg943*) Dutch founder allele that appears homozygously and in compound heterozygosity in the founding LVNC10 case series. 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metabolism in astrocytes underlies degeneration of cortical projection neurons in hereditary spastic paraplegia.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We generated isogenic human pluripotent stem cell (hPSC) lines for two ATL1 missense mutations associated with SPG3A, the most common early-onset autosomal dominant HSP.","explanation":"Describes the isogenic lines behind the model."},{"reference":"PMID:33287888","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33287888","reference_title":"Impaired lipid metabolism in astrocytes underlies degeneration of cortical projection neurons in hereditary spastic paraplegia.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Importantly, ATL1 mutations dysregulated proteolipid gene expression, reduced lipid droplet size in astrocytes, and unexpectedly disrupted cholesterol transfer from glia to neurons, leading to cholesterol deficiency in SPG3A cortical PNs.","explanation":"Reports the lipid-droplet and cholesterol-transfer measurements."},{"reference":"PMID:33287888","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33287888","reference_title":"Impaired lipid metabolism in astrocytes underlies degeneration of cortical projection neurons in hereditary spastic paraplegia.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Applying cholesterol or conditioned medium from control astrocytes, a major source of cholesterol in the brain, rescued aberrant axonal transport and swellings in SPG3A cortical PNs.","explanation":"Reports the rescue measurement."},{"reference":"PMID:33287888","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33287888","reference_title":"Impaired lipid metabolism in astrocytes underlies degeneration of cortical projection neurons in hereditary spastic paraplegia.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Furthermore, treatment with the NR1H2 agonist GW3965 corrected lipid droplet defects in SPG3A astrocytes and promoted cholesterol efflux from astrocytes, leading to restoration of cholesterol levels and rescue of axonal degeneration in SPG3A cortical PNs.","explanation":"Reports the LXR-agonist rescue measurements."},{"reference":"PMID:33287888","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33287888","reference_title":"Impaired lipid metabolism in astrocytes underlies degeneration of cortical projection neurons in hereditary spastic paraplegia.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"In hPSC-derived cortical PNs, ATL1 mutations resulted in reduced axonal outgrowth, impaired axonal transport, and accumulated axonal swellings, recapitulating disease-specific phenotypes.","explanation":"The axonal phenotypes that make the model informative for the transport node."}],"evidence_text":["We generated isogenic human pluripotent stem cell (hPSC) lines for two ATL1 missense mutations associated with SPG3A, the most common early-onset autosomal dominant HSP.","Importantly, ATL1 mutations dysregulated proteolipid gene expression, reduced lipid droplet size in astrocytes, and unexpectedly disrupted cholesterol transfer from glia to neurons, leading to cholesterol deficiency in SPG3A cortical PNs.","Applying cholesterol or conditioned medium from control astrocytes, a major source of cholesterol in the brain, rescued aberrant axonal transport and swellings in SPG3A cortical PNs.","Furthermore, treatment with the NR1H2 agonist GW3965 corrected lipid droplet defects in SPG3A astrocytes and promoted cholesterol efflux from astrocytes, leading to restoration of cholesterol levels and rescue of axonal degeneration in SPG3A cortical PNs.","In hPSC-derived cortical PNs, ATL1 mutations resulted in reduced axonal outgrowth, impaired axonal transport, and accumulated axonal swellings, recapitulating disease-specific phenotypes.","Describes the isogenic lines behind the model.","Reports the lipid-droplet and cholesterol-transfer measurements.","Reports the rescue measurement.","Reports the LXR-agonist rescue measurements.","The axonal phenotypes that make the model informative for the transport node."],"evidence_status":"Evidence recorded","metadata_completeness":60,"metadata_present":["Model category","Organism","Cell type","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Anatomy","Cell source","Culture system"],"dataset_context":"None recorded in same 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White adipocyte and hepatocyte chambers are linked by circulating media at 20 microlitres per hour; proinflammatory (M1) macrophages are added to the adipocyte chamber to impose white adipose tissue inflammation. Because adipose expansion (set by the adipocyte-to-hepatocyte ratio) and adipose inflammation (set by macrophage polarization) are controlled independently, the system can do what whole-animal models cannot: ask which of the two drives hepatic steatosis and hepatic insulin resistance. In this system inflammation, not expansion, is the driver, and the GLP-1 receptor agonist semaglutide improves hepatocyte lipid content and insulin response by acting on the adipocyte compartment rather than on the hepatocyte.","notes":"The compartment-selective result is the part hardest to obtain any other way: using a non-circulating flow-through configuration, semaglutide applied only to the adipocyte compartment reproduced the whole-system benefit, while semaglutide applied only to the hepatocyte compartment did not. The authors note that the same question is confounded in mice by semaglutide's effects on feeding and body weight and by GLP-1 receptor expression across several cell types. This is curated as evidence on the Semaglutide treatment's adipose target_mechanisms edge rather than as a separate mechanism node.","context_id":"disorder:Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease","context_kind":"Disorder","disease_name":"Metabolic Dysfunction-Associated Steatotic Liver Disease","disease_synonyms":["MASLD","Nonalcoholic fatty liver disease","NAFLD","Non-alcoholic fatty liver disease","Metabolic dysfunction-associated fatty liver disease"],"disease_term":{"id":"MONDO:0013209","label":"metabolic dysfunction-associated steatotic liver disease","display_label":"metabolic dysfunction-associated steatotic liver disease","url":"http://purl.obolibrary.org/obo/MONDO_0013209"},"experimental_model_type":"ORGAN_ON_CHIP","experimental_model_type_label":"Organ-on-chip","namo_type":"namo:OrganOnChip","declared_namo_class_name":"OrganOnChip","namo_class_name":"OrganOnChip","namo_class_label":"Organ On Chip","namo_description":"A model system that simulates the physiological functions of an organ using a microfluidic device. Examples: Airway-on-chip, ... Aligned with ISO 10991:2023 microfluidics terminology.","namo_docs_url":"https://monarch-initiative.github.io/namo/elements/OrganOnChip/","namo_ontology_url":"https://w3id.org/monarch-initiative/namo/OrganOnChip","namo_mapping_basis":"Explicit in DisMech","namo_class_in_schema":true,"namo_schema_status":"Defined in NAMO schema used for this build","modality":"Microphysiological system","organism":{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},"organism_label":"Homo sapiens","model_tissue":[{"id":"UBERON:0002107","label":"liver","display_label":"liver","url":"http://purl.obolibrary.org/obo/UBERON_0002107"}],"model_tissue_labels":["liver"],"linked_anatomy":[{"id":"UBERON:0002107","label":"liver","display_label":"liver","url":"http://purl.obolibrary.org/obo/UBERON_0002107"}],"linked_anatomy_labels":["liver"],"anatomy":[{"id":"UBERON:0002107","label":"liver","display_label":"liver","url":"http://purl.obolibrary.org/obo/UBERON_0002107"}],"anatomy_labels":["liver"],"tissue_label":"liver","model_cell_types":[{"id":"CL:0000448","label":"white adipocyte","display_label":"iPSC-derived white adipocyte (iADIPO)","url":"http://purl.obolibrary.org/obo/CL_0000448"},{"id":"CL:0000182","label":"hepatocyte","display_label":"iPSC-derived hepatocyte (iHEP)","url":"http://purl.obolibrary.org/obo/CL_0000182"},{"id":"CL:0000863","label":"M1 macrophage","display_label":"iPSC-derived proinflammatory (M1) macrophage (iMAC)","url":"http://purl.obolibrary.org/obo/CL_0000863"}],"model_cell_type_labels":["white adipocyte","hepatocyte","M1 macrophage"],"linked_cell_types":[{"id":"CL:0000136","label":"adipocyte","display_label":"adipocyte","url":"http://purl.obolibrary.org/obo/CL_0000136"},{"id":"CL:0000182","label":"hepatocyte","display_label":"hepatocyte","url":"http://purl.obolibrary.org/obo/CL_0000182"}],"linked_cell_type_labels":["adipocyte","hepatocyte"],"cell_types":[{"id":"CL:0000448","label":"white adipocyte","display_label":"iPSC-derived white adipocyte (iADIPO)","url":"http://purl.obolibrary.org/obo/CL_0000448"},{"id":"CL:0000182","label":"hepatocyte","display_label":"iPSC-derived hepatocyte (iHEP)","url":"http://purl.obolibrary.org/obo/CL_0000182"},{"id":"CL:0000863","label":"M1 macrophage","display_label":"iPSC-derived proinflammatory (M1) macrophage (iMAC)","url":"http://purl.obolibrary.org/obo/CL_0000863"},{"id":"CL:0000136","label":"adipocyte","display_label":"adipocyte","url":"http://purl.obolibrary.org/obo/CL_0000136"}],"cell_type_labels":["white adipocyte","hepatocyte","M1 macrophage","adipocyte"],"conditions":["white adipose tissue inflammation imposed by proinflammatory macrophages","graded adipose expansion set by adipocyte-to-hepatocyte ratio","hepatic steatosis and hepatic insulin resistance","pharmacological intervention with semaglutide, metformin, rosiglitazone and dexamethasone"],"cell_source":"Isogenic human induced pluripotent stem cell-derived white adipocytes, hepatocytes and macrophages from a single donor line","source_category":"iPSC-derived","culture_system":"Interconnected two-chamber microphysiological system with circulating media at 20 microlitres per hour, and a non-circulating flow-through configuration for compartment-selective drug exposure","publication":"PMID:39266553","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39266553","mechanisms":[{"target":"Cardiometabolic Dysfunction and Adipose Insulin Resistance","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease.html#pathophysiology-cardiometabolic-dysfunction-and-adipose-insulin-resistance","relationship":"RECAPITULATES","relationship_label":"Recapitulates","fidelity":"MODERATE","fidelity_label":"Moderate","description":"Reconstructs the initiating cardiometabolic state of the pathograph in human cells — inflamed, insulin-resistant white adipose tissue releasing fatty acids and TNF-alpha into a circulation shared with the liver — and separates adipose inflammation from adipose expansion as candidate causes, which the trigger node's description leaves bundled.","limitations":"The system carries no vasculature, no immune trafficking beyond the added macrophages, no gut and no central control of feeding, so it models the adipose-to-liver limb of a state that is whole-body in patients. Insulin resistance is imposed over days by macrophage polarization rather than arising from years of overnutrition, and the iPSC-derived cells retain a fetal-like maturation state.","biological_scale":"ORGANISM","anatomy":[],"cell_types":[{"id":"CL:0000136","label":"adipocyte","display_label":"adipocyte","url":"http://purl.obolibrary.org/obo/CL_0000136"},{"id":"CL:0000182","label":"hepatocyte","display_label":"hepatocyte","url":"http://purl.obolibrary.org/obo/CL_0000182"}],"biological_processes":[{"id":"GO:0032869","label":"cellular response to insulin stimulus","display_label":"cellular response to insulin stimulus","url":"http://purl.obolibrary.org/obo/GO_0032869"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Insulin-stimulated glucose uptake in the adipocyte compartment","description":null,"target":"Cardiometabolic Dysfunction and Adipose Insulin Resistance","direction":"DECREASED","interpretation":"Loss of insulin-stimulated glucose uptake is the functional 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suppression of hepatic glucose production","description":null,"target":"Cardiometabolic Dysfunction and Adipose Insulin Resistance","direction":"DECREASED","interpretation":"Failure of insulin to suppress hepatic glucose production is the hepatic limb of the same insulin-resistant state, read out across the fluidic link rather than in the tissue that was manipulated.","biological_processes":[{"id":"GO:0006094","label":"gluconeogenesis","display_label":"gluconeogenesis","url":"http://purl.obolibrary.org/obo/GO_0006094"}],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:39266553","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39266553","reference_title":"Adipocyte inflammation is the primary driver of hepatic insulin resistance in a human iPSC-based microphysiological system.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Analysis of insulin regulation of HGP after 48 h of iADIPO-iHEP-MPS interconnection showed insulin resistance only at the highest iADIPO-iHEP ratio of 30:1","explanation":"Records the expansion arm as the weaker of the two: mass alone produced hepatic insulin resistance only at an extreme ratio, which is the comparison that makes inflammation the primary driver."}],"notes":null}],"evidence":[{"reference":"PMID:39266553","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39266553","reference_title":"Adipocyte inflammation is the primary driver of hepatic insulin resistance in a human iPSC-based microphysiological system.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"we establish an interconnected microphysiological system (MPS) containing white adipocytes, hepatocytes and proinflammatory macrophages derived from isogenic human induced pluripotent stem cells.","explanation":"Establishes that the model contains the adipose, hepatic and inflammatory compartments this trigger node describes, in human cells of a single genotype."},{"reference":"PMID:39266553","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39266553","reference_title":"Adipocyte inflammation is the primary driver of hepatic insulin resistance in a human iPSC-based microphysiological system.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"nor disrupted insulin-mediated regulation of glucose uptake in the iADIPO-MPS or HGP in the iHEP-MPS, similar to control conditions without iMACs","explanation":"The M0 control arm establishes that the loss of insulin-regulated glucose uptake requires proinflammatory polarization specifically, rather than the presence of macrophages."},{"reference":"PMID:39266553","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39266553","reference_title":"Adipocyte inflammation is the primary driver of hepatic insulin resistance in a human iPSC-based microphysiological system.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Analysis of insulin regulation of HGP after 48 h of iADIPO-iHEP-MPS interconnection showed insulin resistance only at the highest iADIPO-iHEP ratio of 30:1","explanation":"Records the expansion arm as the weaker of the two: mass alone produced hepatic insulin resistance only at an extreme ratio, which is the comparison that makes inflammation the primary driver."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease","model_node_id":"model:kb/disorders/Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease.yaml:Isogenic iPSC adipocyte-hepatocyte-macrophage microphysiological system 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In this system inflammation, not expansion, is the driver, and the GLP-1 receptor agonist semaglutide improves hepatocyte lipid content and insulin response by acting on the adipocyte compartment rather than on the hepatocyte.","url":"https://dismech.monarchinitiative.org/pages/disorders/Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease.html#experimental-model-isogenic-ipsc-adipocyte-hepatocyte-macrophage-microphysiological-system-m1-iadipo-ihep-mps","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMetabolic_Dysfunction-Associated_Steatotic_Liver_Disease:pathophysiology:Cardiometabolic%20Dysfunction%20and%20Adipose%20Insulin%20Resistance","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Cardiometabolic Dysfunction and Adipose Insulin Resistance","description":"MASLD is defined by hepatic steatosis in the presence of at least one cardiometabolic risk factor (overweight/obesity, dysglycaemia or type 2 diabetes, hypertension, hypertriglyceridaemia, or low HDL cholesterol). Adipose-tissue insulin resistance fails to restrain lipolysis, so non-esterified fatty acids flood the portal circulation, while hyperinsulinaemia and carbohydrate surplus drive hepatic de novo lipogenesis. This cardiometabolic state is the initiating context that distinguishes MASLD from other steatotic liver diseases.","url":"https://dismech.monarchinitiative.org/pages/disorders/Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease.html#pathophysiology-cardiometabolic-dysfunction-and-adipose-insulin-resistance","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMetabolic_Dysfunction-Associated_Steatotic_Liver_Disease:pathophysiology:Hepatocyte%20Lipid%20Overload","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Hepatocyte Lipid Overload","description":"Hepatocyte triglyceride accumulates when fatty acid inflow from adipose lipolysis and diet, plus de novo lipogenesis, exceeds fatty acid oxidation and very-low-density lipoprotein export. In MASLD the disorder-specific inflow is metabolic (adipose insulin resistance and carbohydrate surplus) rather than ethanol-driven, but the resulting lipid-droplet overload is the conserved module state.","url":"https://dismech.monarchinitiative.org/pages/disorders/Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease.html#pathophysiology-hepatocyte-lipid-overload","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMetabolic_Dysfunction-Associated_Steatotic_Liver_Disease:pathophysiology:Liver%20Sinusoidal%20Endothelial%20Cell%20Dysfunction%20and%20Capillarization","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Liver Sinusoidal Endothelial Cell Dysfunction and Capillarization","description":"Liver sinusoidal endothelial cells (LSECs) are the fenestrated gatekeepers between portal blood and the hepatocyte, and in health they hold Kupffer cells and hepatic stellate cells quiescent. 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This node is the hepatic limb of the endothelial arm; it is not on the canonical lipotoxic backbone and is grouped under the emerging sinusoidal_endothelial_dysfunction_masld hypothesis.","url":"https://dismech.monarchinitiative.org/pages/disorders/Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease.html#pathophysiology-liver-sinusoidal-endothelial-cell-dysfunction-and-capillarization","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMetabolic_Dysfunction-Associated_Steatotic_Liver_Disease:pathophysiology:Transporter-Mediated%20Hepatic%20Fatty%20Acid%20Uptake","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Transporter-Mediated Hepatic Fatty Acid Uptake","description":"Long-chain fatty acids delivered to the liver do not enter hepatocytes by passive diffusion alone. Uptake is largely protein-mediated, through fatty acid transport proteins at the basal plasma membrane of the hepatocyte. FATP5 (SLC27A5) is expressed exclusively by liver and localizes to that membrane; FATP2 (SLC27A2) accounts for a further large share of hepatic long-chain fatty acid uptake while also serving as a peroxisomal very-long-chain acyl-CoA synthetase. This node is deliberately kept separate from Hepatocyte Lipid Overload because it is the step at which the circulating non-esterified fatty acid load is gated, and because it is where the two rodent interventions that reverse established steatosis act. What is increased in the high-fat state is the flux through this step rather than, on the curated evidence, transporter expression: the murine experiments show that continued transporter activity is required to sustain fatty acid entry, not that the transporters are upregulated by disease. The node carries the emerging hepatic-uptake hypothesis and is not asserted as a required step in human disease.","url":"https://dismech.monarchinitiative.org/pages/disorders/Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease.html#pathophysiology-transporter-mediated-hepatic-fatty-acid-uptake","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease.yaml:Isogenic iPSC adipocyte-hepatocyte-macrophage microphysiological system (M1-iADIPO-iHEP-MPS)","source_id":"model:kb/disorders/Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease.yaml:Isogenic iPSC adipocyte-hepatocyte-macrophage microphysiological system (M1-iADIPO-iHEP-MPS)","target_id":"node:disorder%3AMetabolic_Dysfunction-Associated_Steatotic_Liver_Disease:pathophysiology:Cardiometabolic%20Dysfunction%20and%20Adipose%20Insulin%20Resistance","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"Reconstructs the initiating cardiometabolic state of the pathograph in human cells — inflamed, insulin-resistant white adipose tissue releasing fatty acids and TNF-alpha into a circulation shared with the liver — and separates adipose inflammation from adipose expansion as candidate causes, which the trigger node's description leaves bundled.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AMetabolic_Dysfunction-Associated_Steatotic_Liver_Disease:0:0","source_id":"node:disorder%3AMetabolic_Dysfunction-Associated_Steatotic_Liver_Disease:pathophysiology:Cardiometabolic%20Dysfunction%20and%20Adipose%20Insulin%20Resistance","target_id":"node:disorder%3AMetabolic_Dysfunction-Associated_Steatotic_Liver_Disease:pathophysiology:Hepatocyte%20Lipid%20Overload","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Adipose insulin resistance and overnutrition supply the fatty acid inflow and lipogenic drive that produce hepatocyte lipid accumulation.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AMetabolic_Dysfunction-Associated_Steatotic_Liver_Disease:0:2","source_id":"node:disorder%3AMetabolic_Dysfunction-Associated_Steatotic_Liver_Disease:pathophysiology:Cardiometabolic%20Dysfunction%20and%20Adipose%20Insulin%20Resistance","target_id":"node:disorder%3AMetabolic_Dysfunction-Associated_Steatotic_Liver_Disease:pathophysiology:Liver%20Sinusoidal%20Endothelial%20Cell%20Dysfunction%20and%20Capillarization","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[2]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"The same cardiometabolic state that drives hepatocyte lipid loading also acts on the sinusoidal endothelium: insulin resistance and dyslipidaemia exacerbate endothelial activation and lipid handling across vascular and hepatic beds. This edge is what makes the endothelial arm a branch of the shared cardiometabolic trigger rather than a second, unexplained initiating step.","intermediate_mechanisms":[],"hypothesis_groups":["sinusoidal_endothelial_dysfunction_masld"],"evidence_count":1},{"id":"causal:disorder%3AMetabolic_Dysfunction-Associated_Steatotic_Liver_Disease:0:1","source_id":"node:disorder%3AMetabolic_Dysfunction-Associated_Steatotic_Liver_Disease:pathophysiology:Cardiometabolic%20Dysfunction%20and%20Adipose%20Insulin%20Resistance","target_id":"node:disorder%3AMetabolic_Dysfunction-Associated_Steatotic_Liver_Disease:pathophysiology:Transporter-Mediated%20Hepatic%20Fatty%20Acid%20Uptake","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[1]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Unrestrained adipose lipolysis raises the non-esterified fatty acid load presented to the liver, and the transporters at the hepatocyte basal membrane are what convert that circulating load into hepatocellular fatty acid entry. The edge asserts substrate delivery to the transport step, not upregulation of the transporters themselves.","intermediate_mechanisms":[],"hypothesis_groups":["hepatic_fatty_acid_uptake_masld"],"evidence_count":2}]}},{"target":"Hepatocyte Lipid Overload","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease.html#pathophysiology-hepatocyte-lipid-overload","relationship":"RECAPITULATES","relationship_label":"Recapitulates","fidelity":"MODERATE","fidelity_label":"Moderate","description":"Hepatocyte lipid accumulation arises in the chip as a consequence of inflammation in the connected adipose compartment, not from direct fatty acid loading of the hepatocytes, so the model reproduces the causal route into this node rather than only its end state.","limitations":"The readout is intracellular fluorescent fatty acid and lipid content over days, not histologic macrovesicular steatosis; the chip has no stellate cells or Kupffer cells, so nothing downstream of this node — inflammation resolution, ballooning, fibrosis — can be assessed in it.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[{"id":"CL:0000182","label":"hepatocyte","display_label":"hepatocyte","url":"http://purl.obolibrary.org/obo/CL_0000182"}],"biological_processes":[{"id":"GO:0019432","label":"triglyceride biosynthetic process","display_label":"triglyceride biosynthetic process","url":"http://purl.obolibrary.org/obo/GO_0019432"},{"id":"GO:0019915","label":"lipid storage","display_label":"lipid storage","url":"http://purl.obolibrary.org/obo/GO_0019915"},{"id":"GO:0006635","label":"fatty acid beta-oxidation","display_label":"fatty acid beta-oxidation","url":"http://purl.obolibrary.org/obo/GO_0006635"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Hepatocyte fatty acid uptake and lipid accumulation under adipose inflammation","description":null,"target":"Hepatocyte Lipid Overload","direction":"INCREASED","interpretation":"The defining measurement of this node, produced in human cells by a purely upstream adipose manipulation.","biological_processes":[{"id":"GO:0019915","label":"lipid storage","display_label":"lipid storage","url":"http://purl.obolibrary.org/obo/GO_0019915"}],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:39266553","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39266553","reference_title":"Adipocyte inflammation is the primary driver of hepatic insulin resistance in a human iPSC-based microphysiological system.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Consequently, the iHEP-MPS showed increased fatty acid uptake and lipid accumulation under inflamed iADIPO-MPS conditions","explanation":"Reports both the uptake and the accumulation limbs of the hepatocyte response to adipose inflammation."}],"notes":null}],"evidence":[{"reference":"PMID:39266553","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39266553","reference_title":"Adipocyte inflammation is the primary driver of hepatic insulin resistance in a human iPSC-based microphysiological system.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"macrophage-induced adipocyte inflammation causes lipid accumulation in hepatocytes and MPS-wide insulin resistance, corresponding to initiation of metabolic dysfunction-associated steatotic liver disease.","explanation":"The authors' own mapping of the chip's end state onto MASLD initiation, which is what licenses linking it to this node."},{"reference":"PMID:39266553","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39266553","reference_title":"Adipocyte inflammation is the primary driver of hepatic insulin resistance in a human iPSC-based microphysiological system.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Consequently, the iHEP-MPS showed increased fatty acid uptake and lipid accumulation under inflamed iADIPO-MPS conditions","explanation":"Reports both the uptake and the accumulation limbs of the hepatocyte response to adipose inflammation."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease","model_node_id":"model:kb/disorders/Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease.yaml:Isogenic iPSC adipocyte-hepatocyte-macrophage microphysiological system (M1-iADIPO-iHEP-MPS)","focus_node_id":"node:disorder%3AMetabolic_Dysfunction-Associated_Steatotic_Liver_Disease:pathophysiology:Hepatocyte%20Lipid%20Overload","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease.html#pathograph","nodes":[{"id":"model:kb/disorders/Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease.yaml:Isogenic iPSC 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White adipocyte and hepatocyte chambers are linked by circulating media at 20 microlitres per hour; proinflammatory (M1) macrophages are added to the adipocyte chamber to impose white adipose tissue inflammation. Because adipose expansion (set by the adipocyte-to-hepatocyte ratio) and adipose inflammation (set by macrophage polarization) are controlled independently, the system can do what whole-animal models cannot: ask which of the two drives hepatic steatosis and hepatic insulin resistance. In this system inflammation, not expansion, is the driver, and the GLP-1 receptor agonist semaglutide improves hepatocyte lipid content and insulin response by acting on the adipocyte compartment rather than on the hepatocyte.","url":"https://dismech.monarchinitiative.org/pages/disorders/Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease.html#experimental-model-isogenic-ipsc-adipocyte-hepatocyte-macrophage-microphysiological-system-m1-iadipo-ihep-mps","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMetabolic_Dysfunction-Associated_Steatotic_Liver_Disease:pathophysiology:Hepatocyte%20Lipid%20Overload","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Hepatocyte Lipid Overload","description":"Hepatocyte triglyceride accumulates when fatty acid inflow from adipose lipolysis and diet, plus de novo lipogenesis, exceeds fatty acid oxidation and very-low-density lipoprotein export. In MASLD the disorder-specific inflow is metabolic (adipose insulin resistance and carbohydrate surplus) rather than ethanol-driven, but the resulting lipid-droplet overload is the conserved module state.","url":"https://dismech.monarchinitiative.org/pages/disorders/Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease.html#pathophysiology-hepatocyte-lipid-overload","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMetabolic_Dysfunction-Associated_Steatotic_Liver_Disease:pathophysiology:Cardiometabolic%20Dysfunction%20and%20Adipose%20Insulin%20Resistance","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Cardiometabolic Dysfunction and Adipose Insulin Resistance","description":"MASLD is defined by hepatic steatosis in the presence of at least one cardiometabolic risk factor (overweight/obesity, dysglycaemia or type 2 diabetes, hypertension, hypertriglyceridaemia, or low HDL cholesterol). Adipose-tissue insulin resistance fails to restrain lipolysis, so non-esterified fatty acids flood the portal circulation, while hyperinsulinaemia and carbohydrate surplus drive hepatic de novo lipogenesis. This cardiometabolic state is the initiating context that distinguishes MASLD from other steatotic liver diseases.","url":"https://dismech.monarchinitiative.org/pages/disorders/Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease.html#pathophysiology-cardiometabolic-dysfunction-and-adipose-insulin-resistance","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMetabolic_Dysfunction-Associated_Steatotic_Liver_Disease:pathophysiology:Hypoxia-Driven%20Hepatic%20Lipogenesis%20and%20Oxidative%20Stress","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Hypoxia-Driven Hepatic Lipogenesis and Oxidative Stress","description":"Intermittent hypoxia raises hepatic SREBP-1 and its target stearoyl-CoA desaturase 1, increasing triglyceride and phospholipid biosynthesis, and the reoxygenation half of each cycle generates reactive oxygen species so that the hepatocyte experiences a repeated ischemia-reperfusion-like insult. The lipogenic limb is HIF-1-dependent in mice; the oxidative limb is the one measured directly in human liver, as in-situ 4-hydroxynonenal staining and urinary F2-isoprostanes that scale with the nocturnal hypoxia metrics. The node therefore feeds both the lipid-overload state and the injury state of the canonical backbone rather than substituting for either.","url":"https://dismech.monarchinitiative.org/pages/disorders/Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease.html#pathophysiology-hypoxia-driven-hepatic-lipogenesis-and-oxidative-stress","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMetabolic_Dysfunction-Associated_Steatotic_Liver_Disease:pathophysiology:Impaired%20Hepatocyte%20Mitophagy","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Hepatocyte Mitophagy","description":"Mitophagy is the selective autophagic clearance of damaged mitochondria, executed through ubiquitin-dependent (PINK1/Parkin) and ubiquitin-independent receptor pathways. In steatotic hepatocytes this quality-control step is suppressed, so depolarized, reactive-oxygen-species-producing mitochondria persist and NLRP3 inflammasome activation and pyroptotic hepatocyte death are licensed. This node carries the emerging mitophagy hypothesis and is not asserted as a required step in every case.","url":"https://dismech.monarchinitiative.org/pages/disorders/Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease.html#pathophysiology-impaired-hepatocyte-mitophagy","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMetabolic_Dysfunction-Associated_Steatotic_Liver_Disease:pathophysiology:Lipotoxic%20Stress%20and%20Organelle%20Dysfunction","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Lipotoxic Stress and Organelle Dysfunction","description":"Toxic non-triglyceride lipid species (diacylglycerols, ceramides, free fatty acid metabolites) accumulate alongside stored triglyceride and induce endoplasmic reticulum stress, mitochondrial dysfunction, and reactive oxygen species accumulation. This is the amplification step that converts bland steatosis (MASL) toward steatohepatitis (MASH).","url":"https://dismech.monarchinitiative.org/pages/disorders/Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease.html#pathophysiology-lipotoxic-stress-and-organelle-dysfunction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMetabolic_Dysfunction-Associated_Steatotic_Liver_Disease:pathophysiology:Liver%20Sinusoidal%20Endothelial%20Cell%20Dysfunction%20and%20Capillarization","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Liver Sinusoidal Endothelial Cell Dysfunction and Capillarization","description":"Liver sinusoidal endothelial cells (LSECs) are the fenestrated gatekeepers between portal blood and the hepatocyte, and in health they hold Kupffer cells and hepatic stellate cells quiescent. In MASLD they capillarize — losing their fenestrae and their shear-responsive vasodilator output — and lose autophagic capacity, converting them from a restraining influence into a source of inflammatory and fibrogenic mediators. This node is the hepatic limb of the endothelial arm; it is not on the canonical lipotoxic backbone and is grouped under the emerging sinusoidal_endothelial_dysfunction_masld hypothesis.","url":"https://dismech.monarchinitiative.org/pages/disorders/Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease.html#pathophysiology-liver-sinusoidal-endothelial-cell-dysfunction-and-capillarization","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMetabolic_Dysfunction-Associated_Steatotic_Liver_Disease:pathophysiology:PNPLA3%20rs738409%20Genetic%20Susceptibility","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"PNPLA3 rs738409 Genetic Susceptibility","description":"The PNPLA3 rs738409 (I148M) allele increases hepatic triglyceride content and hepatic inflammation, and accounts for much of the ancestry-related variation in susceptibility to fatty liver. It is a susceptibility modifier of lipid retention rather than a necessary or sufficient cause of MASLD.","url":"https://dismech.monarchinitiative.org/pages/disorders/Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease.html#pathophysiology-pnpla3-rs738409-genetic-susceptibility","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMetabolic_Dysfunction-Associated_Steatotic_Liver_Disease:pathophysiology:TM6SF2%20p.Glu167Lys%20Genetic%20Susceptibility","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"TM6SF2 p.Glu167Lys Genetic Susceptibility","description":"The TM6SF2 p.Glu167Lys variant reduces TM6SF2 protein levels and impairs hepatic very-low-density lipoprotein export, raising liver triglyceride while lowering circulating LDL cholesterol and triglycerides. It is the prototypical example of the discordance between hepatic fat accumulation and cardiovascular lipid risk in MASLD.","url":"https://dismech.monarchinitiative.org/pages/disorders/Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease.html#pathophysiology-tm6sf2-p-glu167lys-genetic-susceptibility","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMetabolic_Dysfunction-Associated_Steatotic_Liver_Disease:pathophysiology:Transporter-Mediated%20Hepatic%20Fatty%20Acid%20Uptake","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Transporter-Mediated Hepatic Fatty Acid Uptake","description":"Long-chain fatty acids delivered to the liver do not enter hepatocytes by passive diffusion alone. Uptake is largely protein-mediated, through fatty acid transport proteins at the basal plasma membrane of the hepatocyte. FATP5 (SLC27A5) is expressed exclusively by liver and localizes to that membrane; FATP2 (SLC27A2) accounts for a further large share of hepatic long-chain fatty acid uptake while also serving as a peroxisomal very-long-chain acyl-CoA synthetase. This node is deliberately kept separate from Hepatocyte Lipid Overload because it is the step at which the circulating non-esterified fatty acid load is gated, and because it is where the two rodent interventions that reverse established steatosis act. What is increased in the high-fat state is the flux through this step rather than, on the curated evidence, transporter expression: the murine experiments show that continued transporter activity is required to sustain fatty acid entry, not that the transporters are upregulated by disease. The node carries the emerging hepatic-uptake hypothesis and is not asserted as a required step in human disease.","url":"https://dismech.monarchinitiative.org/pages/disorders/Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease.html#pathophysiology-transporter-mediated-hepatic-fatty-acid-uptake","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:1:model:kb/disorders/Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease.yaml:Isogenic iPSC adipocyte-hepatocyte-macrophage microphysiological system (M1-iADIPO-iHEP-MPS)","source_id":"model:kb/disorders/Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease.yaml:Isogenic iPSC adipocyte-hepatocyte-macrophage microphysiological system 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As on the fibrosis edge, the human results are curated in disagreement rather than chosen between, but the disagreement runs the opposite way here: the largest individual-participant dataset finds apnea severity an independent risk factor for steatosis after adjustment, while the small biopsy-scored cohort finds no association with histological steatosis. The two measure steatosis differently (a noninvasive hepatic steatosis index in 2120 patients versus liver histology in 97), which is the most likely source of the discrepancy and is itself unresolved.","intermediate_mechanisms":["Hepatic SREBP-1 induction","Stearoyl-CoA desaturase 1 upregulation"],"hypothesis_groups":["osa_intermittent_hypoxia_masld"],"evidence_count":3},{"id":"causal:disorder%3AMetabolic_Dysfunction-Associated_Steatotic_Liver_Disease:6:0","source_id":"node:disorder%3AMetabolic_Dysfunction-Associated_Steatotic_Liver_Disease:pathophysiology:Liver%20Sinusoidal%20Endothelial%20Cell%20Dysfunction%20and%20Capillarization","target_id":"node:disorder%3AMetabolic_Dysfunction-Associated_Steatotic_Liver_Disease:pathophysiology:Hepatocyte%20Lipid%20Overload","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[6].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"The defining endothelium-first claim of this arm: capillarization and loss of shear-responsive vasodilator output occur early in the disease and themselves favour steatosis, rather than arising as a consequence of established hepatocyte injury. 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On the emerging hypothesis this step is rate-limiting, so reducing it lowers hepatic triglyceride even while fatty acid inflow to the liver and dietary fat intake continue.","intermediate_mechanisms":[],"hypothesis_groups":["hepatic_fatty_acid_uptake_masld"],"evidence_count":2}]}},{"target":"Transporter-Mediated Hepatic Fatty Acid Uptake","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease.html#pathophysiology-transporter-mediated-hepatic-fatty-acid-uptake","relationship":"MEASURES","relationship_label":"Measures","fidelity":"UNKNOWN","fidelity_label":"Unknown","description":"Fatty acid entry into hepatocytes is measured directly in the chip as accumulation of fluorescent fatty acids, and rises when the connected adipose compartment is inflamed. 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White adipocyte and hepatocyte chambers are linked by circulating media at 20 microlitres per hour; proinflammatory (M1) macrophages are added to the adipocyte chamber to impose white adipose tissue inflammation. Because adipose expansion (set by the adipocyte-to-hepatocyte ratio) and adipose inflammation (set by macrophage polarization) are controlled independently, the system can do what whole-animal models cannot: ask which of the two drives hepatic steatosis and hepatic insulin resistance. In this system inflammation, not expansion, is the driver, and the GLP-1 receptor agonist semaglutide improves hepatocyte lipid content and insulin response by acting on the adipocyte compartment rather than on the hepatocyte.","url":"https://dismech.monarchinitiative.org/pages/disorders/Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease.html#experimental-model-isogenic-ipsc-adipocyte-hepatocyte-macrophage-microphysiological-system-m1-iadipo-ihep-mps","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMetabolic_Dysfunction-Associated_Steatotic_Liver_Disease:pathophysiology:Transporter-Mediated%20Hepatic%20Fatty%20Acid%20Uptake","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Transporter-Mediated Hepatic Fatty Acid Uptake","description":"Long-chain fatty acids delivered to the liver do not enter hepatocytes by passive diffusion alone. 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The node carries the emerging hepatic-uptake hypothesis and is not asserted as a required step in human disease.","url":"https://dismech.monarchinitiative.org/pages/disorders/Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease.html#pathophysiology-transporter-mediated-hepatic-fatty-acid-uptake","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMetabolic_Dysfunction-Associated_Steatotic_Liver_Disease:pathophysiology:Cardiometabolic%20Dysfunction%20and%20Adipose%20Insulin%20Resistance","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Cardiometabolic Dysfunction and Adipose Insulin Resistance","description":"MASLD is defined by hepatic steatosis in the presence of at least one cardiometabolic risk factor (overweight/obesity, dysglycaemia or type 2 diabetes, hypertension, hypertriglyceridaemia, or low HDL cholesterol). 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This cardiometabolic state is the initiating context that distinguishes MASLD from other steatotic liver diseases.","url":"https://dismech.monarchinitiative.org/pages/disorders/Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease.html#pathophysiology-cardiometabolic-dysfunction-and-adipose-insulin-resistance","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMetabolic_Dysfunction-Associated_Steatotic_Liver_Disease:pathophysiology:Hepatocyte%20Lipid%20Overload","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Hepatocyte Lipid Overload","description":"Hepatocyte triglyceride accumulates when fatty acid inflow from adipose lipolysis and diet, plus de novo lipogenesis, exceeds fatty acid oxidation and very-low-density lipoprotein export. 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compartment"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:39266553","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39266553","reference_title":"Adipocyte inflammation is the primary driver of hepatic insulin resistance in a human iPSC-based microphysiological system.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"we establish an interconnected microphysiological system (MPS) containing white adipocytes, hepatocytes and proinflammatory macrophages derived from isogenic human induced pluripotent stem cells.","explanation":"Establishes that the model contains the adipose, hepatic and inflammatory compartments this trigger node describes, in human cells of a single genotype."},{"reference":"PMID:39266553","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39266553","reference_title":"Adipocyte inflammation is the primary driver of hepatic insulin resistance in a human iPSC-based microphysiological system.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"nor disrupted insulin-mediated regulation of glucose uptake in the iADIPO-MPS or HGP in the iHEP-MPS, similar to control conditions without iMACs","explanation":"The M0 control arm establishes that the loss of insulin-regulated glucose uptake requires proinflammatory polarization specifically, rather than the presence of macrophages."},{"reference":"PMID:39266553","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39266553","reference_title":"Adipocyte inflammation is the primary driver of hepatic insulin resistance in a human iPSC-based microphysiological system.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Analysis of insulin regulation of HGP after 48 h of iADIPO-iHEP-MPS interconnection showed insulin resistance only at the highest iADIPO-iHEP ratio of 30:1","explanation":"Records the expansion arm as the weaker of the two: mass alone produced hepatic insulin resistance only at an extreme ratio, which is the comparison that makes inflammation the primary driver."},{"reference":"PMID:39266553","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39266553","reference_title":"Adipocyte inflammation is the primary driver of hepatic insulin resistance in a human iPSC-based microphysiological system.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"macrophage-induced adipocyte inflammation causes lipid accumulation in hepatocytes and MPS-wide insulin resistance, corresponding to initiation of metabolic dysfunction-associated steatotic liver disease.","explanation":"The authors' own mapping of the chip's end state onto MASLD initiation, which is what licenses linking it to this node."},{"reference":"PMID:39266553","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39266553","reference_title":"Adipocyte inflammation is the primary driver of hepatic insulin resistance in a human iPSC-based microphysiological system.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Consequently, the iHEP-MPS showed increased fatty acid uptake and lipid accumulation under inflamed iADIPO-MPS conditions","explanation":"Reports both the uptake and the accumulation limbs of the hepatocyte response to adipose inflammation."},{"reference":"PMID:39266553","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39266553","reference_title":"Adipocyte inflammation is the primary driver of hepatic insulin resistance in a human iPSC-based microphysiological system.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"To reliably quantify lipid accumulation in iHEPs, we first analyzed absorption of fluorescent fatty acids by the PDMS used to build the iHEP-MPS and iADIPO-MPS, which showed no bias for up to 4 days","explanation":"Documents the device-absorption control that makes the fatty acid uptake measurement in this chip interpretable, which is why the model is curated as measuring rather than recapitulating this node."}],"evidence_text":["we establish an interconnected microphysiological system (MPS) containing white adipocytes, hepatocytes and proinflammatory macrophages derived from isogenic human induced pluripotent stem cells.","nor disrupted insulin-mediated regulation of glucose uptake in the iADIPO-MPS or HGP in the iHEP-MPS, similar to control conditions without iMACs","Analysis of insulin regulation of HGP after 48 h of iADIPO-iHEP-MPS interconnection showed insulin resistance only at the highest iADIPO-iHEP ratio of 30:1","macrophage-induced adipocyte inflammation causes lipid accumulation in hepatocytes and MPS-wide insulin resistance, corresponding to initiation of metabolic dysfunction-associated steatotic liver disease.","Consequently, the iHEP-MPS showed increased fatty acid uptake and lipid accumulation under inflamed iADIPO-MPS conditions","To reliably quantify lipid accumulation in iHEPs, we first analyzed absorption of fluorescent fatty acids by the PDMS used to build the iHEP-MPS and iADIPO-MPS, which showed no bias for up to 4 days","Establishes that the model contains the adipose, hepatic and inflammatory compartments this trigger node describes, in human cells of a single genotype.","The M0 control arm establishes that the loss of insulin-regulated glucose uptake requires proinflammatory polarization specifically, rather than the presence of macrophages.","Records the expansion arm as the weaker of the two: mass alone produced hepatic insulin resistance only at an extreme ratio, which is the comparison that makes inflammation the primary driver.","The authors' own mapping of the chip's end state onto MASLD initiation, which is what licenses linking it to this node.","Reports both the uptake and the accumulation limbs of the hepatocyte response to adipose inflammation.","Documents the device-absorption control that makes the fatty acid uptake measurement in this chip interpretable, 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compartment above fluidically connected to an induced pluripotent stem cell-derived hepatocyte compartment by circulating media, with all three cell types from one donor line. Because adipose expansion (set by the adipocyte-to-hepatocyte ratio) and adipose inflammation (set by macrophage polarization) are varied independently, the system separates two variables that animal models confound, and finds inflammation rather than expansion to be the driver of hepatic insulin resistance. It also carries the drug panel: metformin and rosiglitazone improve the hepatic compartment, dexamethasone does not, and the GLP-1 receptor agonist semaglutide works through the adipocyte compartment alone.","notes":"Fully curated for its MASLD arm in the Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease entry, where the same chip is linked to hepatocyte lipid overload and hepatic fatty acid uptake. 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There is no central control of feeding or body weight, which is precisely why the semaglutide result is interpretable here and confounded in rodents.","biological_scale":null,"anatomy":[],"cell_types":[{"id":"CL:0000182","label":"hepatocyte","display_label":"Hepatocyte","url":"http://purl.obolibrary.org/obo/CL_0000182"},{"id":"CL:0000188","label":"cell of skeletal muscle","display_label":"Skeletal Muscle Cell","url":"http://purl.obolibrary.org/obo/CL_0000188"},{"id":"CL:0000136","label":"adipocyte","display_label":"Adipocyte","url":"http://purl.obolibrary.org/obo/CL_0000136"}],"biological_processes":[{"id":"GO:0008286","label":"insulin receptor signaling pathway","display_label":"Insulin Signaling","url":"http://purl.obolibrary.org/obo/GO_0008286"}],"pathways":[],"genes":[{"id":"hgnc:9236","label":"PPARG","display_label":"PPARG","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/9236"}],"chemicals":[],"readouts":[{"name":"Insulin suppression of hepatic glucose production under adipose inflammation","description":null,"target":"Insulin Resistance","direction":"DECREASED","interpretation":"Measured in the hepatocyte compartment after manipulating only the adipose compartment, so it reads the transfer of insulin resistance between tissues rather than a cell-autonomous defect.","biological_processes":[{"id":"GO:0008286","label":"insulin receptor signaling pathway","display_label":"Insulin Receptor Signaling","url":"http://purl.obolibrary.org/obo/GO_0008286"}],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:39266553","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39266553","reference_title":"Adipocyte inflammation is the primary driver of hepatic insulin resistance in a human iPSC-based microphysiological system.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Analysis of insulin regulation of HGP after 48 h of iADIPO-iHEP-MPS interconnection showed insulin resistance only at the highest iADIPO-iHEP ratio of 30:1","explanation":"The expansion arm, recorded as the weaker of the two: mass alone produced hepatic insulin resistance only at an extreme ratio, which is the comparison that makes inflammation the primary driver."}],"notes":null}],"evidence":[{"reference":"PMID:39266553","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39266553","reference_title":"Adipocyte inflammation is the primary driver of hepatic insulin resistance in a human iPSC-based microphysiological system.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"macrophage-induced adipocyte inflammation causes lipid accumulation in hepatocytes and MPS-wide insulin resistance, corresponding to initiation of metabolic dysfunction-associated steatotic liver disease.","explanation":"States that the manipulation produces system-wide insulin resistance, which is the node this link asserts the model is informative for."},{"reference":"PMID:39266553","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39266553","reference_title":"Adipocyte inflammation is the primary driver of hepatic insulin resistance in a human iPSC-based microphysiological system.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Analysis of insulin regulation of HGP after 48 h of iADIPO-iHEP-MPS interconnection showed insulin resistance only at the highest iADIPO-iHEP ratio of 30:1","explanation":"The expansion arm, recorded as the weaker of the two: mass alone produced hepatic insulin resistance only at an extreme ratio, which is the comparison that makes inflammation the primary driver."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Type_2_Diabetes_Mellitus","model_node_id":"model:kb/disorders/Type_2_Diabetes_Mellitus.yaml:Isogenic iPSC adipocyte-hepatocyte-macrophage microphysiological system (M1-iADIPO-iHEP-MPS)","focus_node_id":"node:disorder%3AType_2_Diabetes_Mellitus:pathophysiology:Insulin%20Resistance","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Type_2_Diabetes_Mellitus.html#pathograph","nodes":[{"id":"model:kb/disorders/Type_2_Diabetes_Mellitus.yaml:Isogenic iPSC adipocyte-hepatocyte-macrophage microphysiological system (M1-iADIPO-iHEP-MPS)","kind":"experimental_model","kind_label":"NAM model","label":"Isogenic iPSC adipocyte-hepatocyte-macrophage microphysiological system (M1-iADIPO-iHEP-MPS)","description":"The adipose compartment above fluidically connected to an induced pluripotent stem cell-derived hepatocyte compartment by circulating media, with all three cell types from one donor line. 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It also carries the drug panel: metformin and rosiglitazone improve the hepatic compartment, dexamethasone does not, and the GLP-1 receptor agonist semaglutide works through the adipocyte compartment alone.","url":"https://dismech.monarchinitiative.org/pages/disorders/Type_2_Diabetes_Mellitus.html#experimental-model-isogenic-ipsc-adipocyte-hepatocyte-macrophage-microphysiological-system-m1-iadipo-ihep-mps","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AType_2_Diabetes_Mellitus:pathophysiology:Insulin%20Resistance","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Insulin Resistance","description":"Peripheral tissues (muscle, liver, adipose) become resistant to insulin action, requiring higher insulin levels to maintain glucose homeostasis. 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The liver fails to respond appropriately to insulin signals.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Type_2_Diabetes_Mellitus.html#pathophysiology-hepatic-glucose-overproduction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AType_2_Diabetes_Mellitus:pathophysiology:Impaired%20GLUT4-Mediated%20Glucose%20Uptake","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired GLUT4-Mediated Glucose Uptake","description":"Dysregulation of GLUT4 trafficking in adipocytes and skeletal muscle reduces insulin-stimulated glucose uptake. GULP1 facilitates GLUT4 translocation to the plasma membrane by counteracting ACAP1 inhibition of ARF6 activity. Reduced GULP1 activity therefore decreases peripheral glucose disposal and contributes to systemic insulin resistance. TBC1D4 is bound here as the human-genetic entry point to the same step: muscle biopsies show TBC1D4 and GLUT4 protein falling with increasing count of the common Greenlandic p.Arg684Ter allele, alongside severely decreased insulin-stimulated glucose uptake in muscle.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Type_2_Diabetes_Mellitus.html#pathophysiology-impaired-glut4-mediated-glucose-uptake","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AType_2_Diabetes_Mellitus:pathophysiology:White%20Adipose%20Tissue%20Inflammation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"White Adipose Tissue Inflammation","description":"With expanding adiposity, bone-marrow-derived macrophages accumulate in white adipose tissue, shift toward classical (M1) proinflammatory activation, and surround damaged adipocytes as crown-like structures. 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Alongside GLUT4, insulin drives translocation of fatty acid transport proteins — FATP1 (SLC27A1) and FATP4 (SLC27A4) — from an intracellular perinuclear compartment to the plasma membrane within minutes, and long-chain fatty acid uptake rises in parallel. In FATP1-null adipocytes the insulin-stimulated component of fatty acid uptake is entirely absent while basal uptake is unaffected, so FATP1 specifically carries the hormone-responsive arm. Tumor necrosis factor alpha from inflamed adipose tissue suppresses this arm and lowers FATP1 and FATP4 protein. This node is deliberately terminal. Whether losing the arm drives systemic insulin resistance is genuinely unsettled — FATP1-null mice, which lack it from birth, are completely protected from diet-induced insulin desensitization — so no edge is drawn into Insulin Resistance and the tension is carried by the kgap_t2d_fatp1_insulin_stimulated_fatty_acid_uptake discussion instead. The node is curated because it is a real, measurable arm of adipocyte insulin action that the entry otherwise omits, and because it is one of the three functional assays the human adipose microphysiological systems use to score insulin sensitivity.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Type_2_Diabetes_Mellitus.html#pathophysiology-insulin-stimulated-adipocyte-fatty-acid-uptake-via-fatp1","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:1:model:kb/disorders/Type_2_Diabetes_Mellitus.yaml:Isogenic iPSC adipocyte-hepatocyte-macrophage microphysiological system (M1-iADIPO-iHEP-MPS)","source_id":"model:kb/disorders/Type_2_Diabetes_Mellitus.yaml:Isogenic iPSC adipocyte-hepatocyte-macrophage microphysiological system (M1-iADIPO-iHEP-MPS)","target_id":"node:disorder%3AType_2_Diabetes_Mellitus:pathophysiology:White%20Adipose%20Tissue%20Inflammation","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[1]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"Carries the same inflamed adipose compartment as the two-cell system, now with a downstream tissue attached, so the consequences of this node can be measured outside the tissue in which it occurs.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AType_2_Diabetes_Mellitus:0:0","source_id":"node:disorder%3AType_2_Diabetes_Mellitus:pathophysiology:White%20Adipose%20Tissue%20Inflammation","target_id":"node:disorder%3AType_2_Diabetes_Mellitus:ambiguous:Insulin%20Resistance","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Macrophage-derived tumor necrosis factor alpha and the accompanying cytokines impair insulin action in adipose tissue and, through cytokine and fatty acid export, in muscle and liver. 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Absolute production rates in an iPSC-derived hepatocyte compartment are not calibrated against human liver.","biological_scale":null,"anatomy":[],"cell_types":[{"id":"CL:0000182","label":"hepatocyte","display_label":"Hepatocyte","url":"http://purl.obolibrary.org/obo/CL_0000182"}],"biological_processes":[{"id":"GO:0006094","label":"gluconeogenesis","display_label":"Gluconeogenesis","url":"http://purl.obolibrary.org/obo/GO_0006094"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"PCK1 expression and hepatic glucose production","description":null,"target":"Hepatic Glucose Overproduction","direction":"INCREASED","interpretation":"Rising gluconeogenic gene expression alongside loss of insulin suppression is the molecular and functional pair this node describes.","biological_processes":[{"id":"GO:0008286","label":"insulin receptor signaling pathway","display_label":"Insulin Receptor Signaling","url":"http://purl.obolibrary.org/obo/GO_0008286"}],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:39266553","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39266553","reference_title":"Adipocyte inflammation is the primary driver of hepatic insulin resistance in a human iPSC-based microphysiological system.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"whereas PCK1 gene expression was increased in the iHEP-MPS, suggesting activation of gluconeogenesis and development of insulin resistance","explanation":"The gluconeogenic readout in the hepatocyte compartment, which is the content of this node."}],"notes":null}],"evidence":[{"reference":"PMID:39266553","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39266553","reference_title":"Adipocyte inflammation is the primary driver of hepatic insulin resistance in a human iPSC-based microphysiological system.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We found that inclusion of iADIPOs worsened the metabolic alterations in iHEP-MPS, including higher HGP, earlier onset of insulin resistance, higher lipid levels and higher expression of genes reflecting inflammation, gluconeogenesis, lipogenesis and lipid transport","explanation":"Names hepatic glucose production as a measured endpoint that responds to the adipose manipulation, which is why this model is linked to the hepatic node."},{"reference":"PMID:39266553","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39266553","reference_title":"Adipocyte inflammation is the primary driver of hepatic insulin resistance in a human iPSC-based microphysiological system.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"whereas PCK1 gene expression was increased in the iHEP-MPS, suggesting activation of gluconeogenesis and development of insulin resistance","explanation":"The gluconeogenic readout in the hepatocyte compartment, which is the content of this node."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Type_2_Diabetes_Mellitus","model_node_id":"model:kb/disorders/Type_2_Diabetes_Mellitus.yaml:Isogenic iPSC adipocyte-hepatocyte-macrophage microphysiological system (M1-iADIPO-iHEP-MPS)","focus_node_id":"node:disorder%3AType_2_Diabetes_Mellitus:pathophysiology:Hepatic%20Glucose%20Overproduction","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Type_2_Diabetes_Mellitus.html#pathograph","nodes":[{"id":"model:kb/disorders/Type_2_Diabetes_Mellitus.yaml:Isogenic iPSC adipocyte-hepatocyte-macrophage microphysiological system (M1-iADIPO-iHEP-MPS)","kind":"experimental_model","kind_label":"NAM model","label":"Isogenic iPSC adipocyte-hepatocyte-macrophage microphysiological system (M1-iADIPO-iHEP-MPS)","description":"The adipose compartment above fluidically connected to an induced pluripotent stem cell-derived hepatocyte compartment by circulating media, with all three cell types from one donor line. Because adipose expansion (set by the adipocyte-to-hepatocyte ratio) and adipose inflammation (set by macrophage polarization) are varied independently, the system separates two variables that animal models confound, and finds inflammation rather than expansion to be the driver of hepatic insulin resistance. It also carries the drug panel: metformin and rosiglitazone improve the hepatic compartment, dexamethasone does not, and the GLP-1 receptor agonist semaglutide works through the adipocyte compartment alone.","url":"https://dismech.monarchinitiative.org/pages/disorders/Type_2_Diabetes_Mellitus.html#experimental-model-isogenic-ipsc-adipocyte-hepatocyte-macrophage-microphysiological-system-m1-iadipo-ihep-mps","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AType_2_Diabetes_Mellitus:pathophysiology:Hepatic%20Glucose%20Overproduction","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Hepatic Glucose Overproduction","description":"Impaired suppression of hepatic gluconeogenesis leads to elevated fasting glucose levels. The liver fails to respond appropriately to insulin signals.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Type_2_Diabetes_Mellitus.html#pathophysiology-hepatic-glucose-overproduction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AType_2_Diabetes_Mellitus:phenotype:Hyperglycemia","kind":"phenotype","kind_label":"Phenotype","label":"Hyperglycemia","description":null,"url":"https://dismech.monarchinitiative.org/pages/disorders/Type_2_Diabetes_Mellitus.html#phenotype-hyperglycemia","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AType_2_Diabetes_Mellitus:pathophysiology:Insulin%20Resistance","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Insulin Resistance","description":"Peripheral tissues (muscle, liver, adipose) become resistant to insulin action, requiring higher insulin levels to maintain glucose homeostasis. This leads to compensatory hyperinsulinemia and eventually beta cell exhaustion.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Type_2_Diabetes_Mellitus.html#pathophysiology-insulin-resistance","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:2:model:kb/disorders/Type_2_Diabetes_Mellitus.yaml:Isogenic iPSC adipocyte-hepatocyte-macrophage microphysiological system (M1-iADIPO-iHEP-MPS)","source_id":"model:kb/disorders/Type_2_Diabetes_Mellitus.yaml:Isogenic iPSC adipocyte-hepatocyte-macrophage microphysiological system (M1-iADIPO-iHEP-MPS)","target_id":"node:disorder%3AType_2_Diabetes_Mellitus:pathophysiology:Hepatic%20Glucose%20Overproduction","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[2]","label":"Measures","directed":false,"relationship":"MEASURES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"Hepatic glucose production and its suppression by insulin are primary endpoints of the chip, alongside PCK1 expression, so this node has a direct human non-animal assay. 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homeostasis.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AType_2_Diabetes_Mellitus:3:1","source_id":"node:disorder%3AType_2_Diabetes_Mellitus:pathophysiology:Insulin%20Resistance","target_id":"node:disorder%3AType_2_Diabetes_Mellitus:pathophysiology:Hepatic%20Glucose%20Overproduction","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[3].downstream[1]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Hepatic insulin resistance reduces insulin-mediated suppression of liver glucose production.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1}]}}],"mechanism_names":["Insulin Resistance","White Adipose Tissue Inflammation","Hepatic Glucose 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production"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:39266553","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39266553","reference_title":"Adipocyte inflammation is the primary driver of hepatic insulin resistance in a human iPSC-based microphysiological system.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"macrophage-induced adipocyte inflammation causes lipid accumulation in hepatocytes and MPS-wide insulin resistance, corresponding to initiation of metabolic dysfunction-associated steatotic liver disease.","explanation":"States that the manipulation produces system-wide insulin resistance, which is the node this link asserts the model is informative for."},{"reference":"PMID:39266553","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39266553","reference_title":"Adipocyte inflammation is the primary driver of hepatic insulin resistance in a human iPSC-based microphysiological system.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Analysis of insulin regulation of HGP after 48 h of iADIPO-iHEP-MPS interconnection showed insulin resistance only at the highest iADIPO-iHEP ratio of 30:1","explanation":"The expansion arm, recorded as the weaker of the two: mass alone produced hepatic insulin resistance only at an extreme ratio, which is the comparison that makes inflammation the primary driver."},{"reference":"PMID:39266553","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39266553","reference_title":"Adipocyte inflammation is the primary driver of hepatic insulin resistance in a human iPSC-based microphysiological system.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Consistent with our previous results8,34 and human studies44, our model shows that M1-iMAC-mediated inflammation readily induces metabolic dysfunction, including increased WAT lipolysis and induction of systemic insulin resistance.","explanation":"The authors' own statement that the inflamed adipose compartment drives lipolysis and systemic insulin resistance, which is what this node asserts."},{"reference":"PMID:39266553","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39266553","reference_title":"Adipocyte inflammation is the primary driver of hepatic insulin resistance in a human iPSC-based microphysiological system.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"As expected, inflammation markers were increased in the M1-iADIPO-MPS, including gene expression of the proinflammatory cytokine TNF.","explanation":"Confirms the cytokine content of the inflamed adipose compartment in this configuration."},{"reference":"PMID:39266553","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39266553","reference_title":"Adipocyte inflammation is the primary driver of hepatic insulin resistance in a human iPSC-based microphysiological system.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We found that inclusion of iADIPOs worsened the metabolic alterations in iHEP-MPS, including higher HGP, earlier onset of insulin resistance, higher lipid levels and higher expression of genes reflecting inflammation, gluconeogenesis, lipogenesis and lipid transport","explanation":"Names hepatic glucose production as a measured endpoint that responds to the adipose manipulation, which is why this model is linked to the hepatic node."},{"reference":"PMID:39266553","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39266553","reference_title":"Adipocyte inflammation is the primary driver of hepatic insulin resistance in a human iPSC-based microphysiological system.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"whereas PCK1 gene expression was increased in the iHEP-MPS, suggesting activation of gluconeogenesis and development of insulin resistance","explanation":"The gluconeogenic readout in the hepatocyte compartment, which is the content of this node."}],"evidence_text":["macrophage-induced adipocyte inflammation causes lipid accumulation in hepatocytes and MPS-wide insulin resistance, corresponding to initiation of metabolic dysfunction-associated steatotic liver disease.","Analysis of insulin regulation of HGP after 48 h of iADIPO-iHEP-MPS interconnection showed insulin resistance only at the highest iADIPO-iHEP ratio of 30:1","Consistent with our previous results8,34 and human studies44, our model shows that M1-iMAC-mediated inflammation readily induces metabolic dysfunction, including increased WAT lipolysis and induction of systemic insulin resistance.","As expected, inflammation markers were increased in the M1-iADIPO-MPS, including gene expression of the proinflammatory cytokine TNF.","We found that inclusion of iADIPOs worsened the metabolic alterations in iHEP-MPS, including higher HGP, earlier onset of insulin resistance, higher lipid levels and higher expression of genes reflecting inflammation, gluconeogenesis, lipogenesis and lipid transport","whereas PCK1 gene expression was increased in the iHEP-MPS, suggesting activation of gluconeogenesis and development of insulin resistance","States that the manipulation produces system-wide insulin resistance, which is the node this link asserts the model is informative for.","The expansion arm, recorded as the weaker of the two: mass alone produced hepatic insulin resistance only at an extreme ratio, which is the comparison that makes inflammation the primary driver.","The authors' own statement that the inflamed adipose compartment drives lipolysis and systemic insulin resistance, which is what this node asserts.","Confirms the cytokine content of the inflamed adipose compartment in this configuration.","Names hepatic glucose production as a measured endpoint that responds to the adipose manipulation, which is why this model is linked to the hepatic node.","The gluconeogenic readout in the hepatocyte compartment, which is the content of this node."],"evidence_status":"Evidence recorded","metadata_completeness":100,"metadata_present":["Model category","NAMO class","Organism","Anatomy","Cell type","Cell source","Culture system","Modeled mechanism","Publication","Evidence"],"metadata_missing":[],"dataset_context":"Available in same entry","context_dataset_ids":["dataset:bioproject:prjna361402","dataset:bioproject:prjna422434","dataset:bioproject:prjna554535","dataset:bioproject:prjna607849"],"candidate_dataset_ids":[],"source_path":"kb/disorders/Type_2_Diabetes_Mellitus.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Type_2_Diabetes_Mellitus.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Type_2_Diabetes_Mellitus.html#experimental-model-isogenic-ipsc-adipocyte-hepatocyte-macrophage-microphysiological-system-m1-iadipo-ihep-mps","source_anchor":"experimental-model-isogenic-ipsc-adipocyte-hepatocyte-macrophage-microphysiological-system-m1-iadipo-ihep-mps"},{"id":"model:kb/disorders/Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease.yaml:Isogenic iPSC macrophage-adipocyte microphysiological system (iMAC-iADIPO-MPS)","name":"Isogenic iPSC macrophage-adipocyte microphysiological system (iMAC-iADIPO-MPS)","description":"The adipose half of the platform, used on its own to model chronic white adipose tissue inflammation. iPSC-derived macrophages migrate into three-dimensional adipocyte clusters and form crown-like structures around damaged adipocytes, reproducing the defining histology of obese human adipose tissue; the number of such structures rises with adipocyte age and with palmitic acid exposure, so inflammatory severity is gradable. Polarization is the operative variable: M1 but not M2 macrophages induce adipocyte insulin resistance and dysregulated lipolysis, and transcriptomics and cytokine profiling identify a reciprocal proinflammatory loop between the two cell types.","notes":null,"context_id":"disorder:Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease","context_kind":"Disorder","disease_name":"Metabolic Dysfunction-Associated Steatotic Liver Disease","disease_synonyms":["MASLD","Nonalcoholic fatty liver disease","NAFLD","Non-alcoholic fatty liver disease","Metabolic dysfunction-associated fatty liver disease"],"disease_term":{"id":"MONDO:0013209","label":"metabolic dysfunction-associated steatotic liver disease","display_label":"metabolic dysfunction-associated steatotic liver disease","url":"http://purl.obolibrary.org/obo/MONDO_0013209"},"experimental_model_type":"ORGAN_ON_CHIP","experimental_model_type_label":"Organ-on-chip","namo_type":"namo:OrganOnChip","declared_namo_class_name":"OrganOnChip","namo_class_name":"OrganOnChip","namo_class_label":"Organ On Chip","namo_description":"A model system that simulates the physiological functions of an organ using a microfluidic device. 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When cMyBP-C is reduced or absent, this brake is released: myofilament calcium sensitivity rises and the contraction-relaxation cycle is disturbed, producing hypercontractility with impaired relaxation. Direct calcium-handling consequences follow, with progressively slowed calcium release as cMyBP-C content falls.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_4.html#pathophysiology-loss-of-the-cmybp-c-brake-on-actin-myosin-cross-bridge-cycling","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_4:pathophysiology:Gene-Dosage-Dependent%20Severity%20Gradient","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Gene-Dosage-Dependent Severity Gradient","description":"CMH4 severity is a graded function of residual cMyBP-C, and this is the axis that separates the two clinical entities within the same MONDO term. 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Isogenic human engineered cardiac tissue and heterozygous/homozygous knock-in mouse models both reproduce this dose-severity relationship, providing experimental confirmation of the human genotype-phenotype pattern.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_4.html#pathophysiology-gene-dosage-dependent-severity-gradient","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_4:pathophysiology:Myosin%20Shift%20from%20the%20Super-Relaxed%20to%20the%20Disordered-Relaxed%20State","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Myosin Shift from the Super-Relaxed to the Disordered-Relaxed State","description":"In the resting sarcomere a substantial fraction of myosin heads sit in the super-relaxed (SRX) state - folded back against the thick filament core with a very low ATPase rate - forming an energy-conserving reserve of motors that are unavailable for force generation. cMyBP-C is what holds them there. Losing cMyBP-C untethers those heads and shifts the population toward the disordered-relaxed (DRX) state, which can hydrolyse ATP and engage the thin filament. This is the step that converts a protein-dose deficit into hypercontractility with raised energetic cost, and it is the step the approved cardiac myosin inhibitors act on: the same work that defines the SRX loss shows that MYK-461 (mavacamten) rescues the relaxation defect and restores normal contractility in MYBPC3-mutant cardiomyocytes. The shift is demonstrated in three independent systems - homozygous cMyBP-C knockout mouse cardiomyocytes, human MYBPC3-mutant myectomy tissue, and stepwise cMyBP-C depletion in vitro - and, importantly for the dose model, the human myectomy data show a positive correlation between residual cMyBP-C expression and the proportion of heads remaining in SRX.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_4.html#pathophysiology-myosin-shift-from-the-super-relaxed-to-the-disordered-relaxed-state","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:1:model:kb/disorders/Hypertrophic_Cardiomyopathy_4.yaml:Isogenic MYBPC3 +/- and -/- human iPSC engineered cardiac tissue","source_id":"model:kb/disorders/Hypertrophic_Cardiomyopathy_4.yaml:Isogenic MYBPC3 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truncating.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3AHypertrophic_Cardiomyopathy_4:2:0","source_id":"node:disorder%3AHypertrophic_Cardiomyopathy_4:pathophysiology:Myosin%20Shift%20from%20the%20Super-Relaxed%20to%20the%20Disordered-Relaxed%20State","target_id":"node:disorder%3AHypertrophic_Cardiomyopathy_4:pathophysiology:Loss%20of%20the%20cMyBP-C%20Brake%20on%20Actin-Myosin%20Cross-Bridge%20Cycling","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Heads released from the super-relaxed reserve are available to form cross-bridges, so the restraint on cross-bridge number and kinetics is lost.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0}]}}],"mechanism_names":["Gene-Dosage-Dependent Severity Gradient","Loss of the cMyBP-C Brake on Actin-Myosin Cross-Bridge Cycling"],"relationships":["Not Specified"],"fidelities":["Not Specified"],"biological_scales":["Cellular","Molecular"],"system_context_sources":["Linked mechanism cell type","Linked mechanism biological scale"],"modeled_system_labels":["cardiac muscle cell","regular ventricular cardiac myocyte","Cellular","Molecular"],"biological_process_terms":[{"id":"GO:0086003","label":"cardiac muscle cell contraction","display_label":"Cardiac Muscle Cell Contraction","url":"http://purl.obolibrary.org/obo/GO_0086003"},{"id":"GO:0033275","label":"actin-myosin filament sliding","display_label":"Actin-Myosin Filament Sliding","url":"http://purl.obolibrary.org/obo/GO_0033275"},{"id":"GO:0055117","label":"regulation of cardiac muscle contraction","display_label":"Regulation of Cardiac Muscle 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entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Hypertrophic_Cardiomyopathy_4.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hypertrophic_Cardiomyopathy_4.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_4.html#experimental-model-isogenic-mybpc3-and-human-ipsc-engineered-cardiac-tissue","source_anchor":"experimental-model-isogenic-mybpc3-and-human-ipsc-engineered-cardiac-tissue"},{"id":"model:kb/disorders/OPTN-related_Open_Angle_Glaucoma.yaml:Isogenic OPTN(E50K) human pluripotent stem cell-derived retinal ganglion cells","name":"Isogenic OPTN(E50K) human pluripotent stem cell-derived retinal ganglion cells","description":"Human pluripotent stem cell lines in isogenic pairs - patient-derived iPSCs with the E50K mutation corrected, and an H7 embryonic line with E50K introduced by CRISPR/Cas9 - differentiated through retinal organoids into purified retinal ganglion cells. Because the comparison is isogenic, the phenotype is attributable to the OPTN genotype rather than to line background, and because the cells are human ganglion cells it addresses the species limitations of the mouse models directly. Mutant cells show impaired autophagic-lysosomal degradation, AMPK activation, reduced mTORC1 signalling and neurodegenerative features; mTOR-independent autophagy induction rescues neurite outgrowth.\n","notes":null,"context_id":"disorder:OPTN-related_Open_Angle_Glaucoma","context_kind":"Disorder","disease_name":"OPTN-related Open Angle Glaucoma","disease_synonyms":["glaucoma 1, open angle, E","GLC1E","OPTN-related normal tension glaucoma","optineurin-associated normal tension glaucoma"],"disease_term":{"id":"MONDO:0100553","label":"OPTN-related open angle glaucoma","display_label":"OPTN-related open angle glaucoma","url":"http://purl.obolibrary.org/obo/MONDO_0100553"},"experimental_model_type":"IPSC_DERIVED_MODEL","experimental_model_type_label":"iPSC-derived model","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[{"id":"CL:0000740","label":"retinal ganglion cell","display_label":"Retinal Ganglion Cell","url":"http://purl.obolibrary.org/obo/CL_0000740"}],"linked_cell_type_labels":["retinal ganglion cell"],"cell_types":[{"id":"CL:0000740","label":"retinal ganglion cell","display_label":"Retinal Ganglion Cell","url":"http://purl.obolibrary.org/obo/CL_0000740"}],"cell_type_labels":["retinal ganglion cell"],"conditions":[],"cell_source":null,"source_category":"iPSC-derived","culture_system":null,"publication":null,"publication_url":null,"mechanisms":[{"target":"Impaired Autophagic Flux in Retinal Ganglion Cells","target_url":"https://dismech.monarchinitiative.org/pages/disorders/OPTN-related_Open_Angle_Glaucoma.html#pathophysiology-impaired-autophagic-flux-in-retinal-ganglion-cells","relationship":"RECAPITULATES","relationship_label":"Recapitulates","fidelity":"HIGH","fidelity_label":"High","description":"Human retinal ganglion cells with the disease genotype reproduce the autophagic-lysosomal degradation block, in an isogenic comparison.\n","limitations":"hPSC-derived retinal ganglion cells are developmentally immature relative to the adult neurons that degenerate in a disease of middle age, and they are cultured without the optic nerve head, lamina cribrosa, glia and vasculature of the intact eye. The model therefore speaks to the cell-autonomous proteostatic lesion, not to the tissue-level neuropathy.\n","biological_scale":"CELLULAR","anatomy":[],"cell_types":[{"id":"CL:0000740","label":"retinal ganglion cell","display_label":"Retinal Ganglion Cell","url":"http://purl.obolibrary.org/obo/CL_0000740"}],"biological_processes":[{"id":"GO:0016236","label":"macroautophagy","display_label":"Macroautophagy","url":"http://purl.obolibrary.org/obo/GO_0016236"},{"id":"GO:0061909","label":"autophagosome-lysosome fusion","display_label":"Autophagosome-Lysosome Fusion","url":"http://purl.obolibrary.org/obo/GO_0061909"},{"id":"GO:0038202","label":"TORC1 signaling","display_label":"mTORC1 Signalling","url":"http://purl.obolibrary.org/obo/GO_0038202"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Autophagic-lysosomal degradation and mTORC1 signalling","description":null,"target":"Impaired Autophagic Flux in Retinal Ganglion Cells","direction":"DECREASED","interpretation":"Reduced degradative flux with concurrent AMPK activation and lowered mTORC1 signalling in mutant human ganglion cells.\n","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:39425218","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39425218","reference_title":"Acquisition of neurodegenerative features in isogenic OPTN(E50K) human stem cell-derived retinal ganglion cells associated with autophagy disruption and mTORC1 signaling reduction.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We identified an impairment of autophagic-lysosomal degradation and decreased mTORC1 signaling via activation of the stress sensor AMPK, along with subsequent neurodegeneration in OPTN(E50K) RGCs differentiated from hPSCs","explanation":"Reports both measurements recorded in this readout.\n"}],"notes":null},{"name":"Neurite outgrowth after mTOR-independent autophagy induction","description":null,"target":"Impaired Autophagic Flux in Retinal Ganglion Cells","direction":"RESTORED","interpretation":"Rescue on forcing flux, which is what makes the flux block causal for the degenerative phenotype rather than merely correlated with it.\n","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:39425218","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39425218","reference_title":"Acquisition of neurodegenerative features in isogenic OPTN(E50K) human stem cell-derived retinal ganglion cells associated with autophagy disruption and mTORC1 signaling reduction.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"the mTOR-independent induction of autophagy reduced protein accumulation and restored neurite outgrowth in diseased OPTN(E50K) RGCs","explanation":"Reports the rescue that this readout measures.\n"}],"notes":null}],"evidence":[{"reference":"PMID:39425218","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39425218","reference_title":"Acquisition of neurodegenerative features in isogenic OPTN(E50K) human stem cell-derived retinal ganglion cells associated with autophagy disruption and mTORC1 signaling reduction.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Taken together, these results highlighted that autophagy disruption resulted in increased autophagic demand which was associated with downregulated signaling through mTORC1, contributing to the degeneration of RGCs.","explanation":"The study's own conclusion that this human model demonstrates the autophagy-disruption node it is linked to.\n"},{"reference":"PMID:39425218","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39425218","reference_title":"Acquisition of neurodegenerative features in isogenic OPTN(E50K) human stem cell-derived retinal ganglion cells associated with autophagy disruption and mTORC1 signaling reduction.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We identified an impairment of autophagic-lysosomal degradation and decreased mTORC1 signaling via activation of the stress sensor AMPK, along with subsequent neurodegeneration in OPTN(E50K) RGCs differentiated from hPSCs","explanation":"Reports both measurements recorded in this readout.\n"},{"reference":"PMID:39425218","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39425218","reference_title":"Acquisition of neurodegenerative features in isogenic OPTN(E50K) human stem cell-derived retinal ganglion cells associated with autophagy disruption and mTORC1 signaling reduction.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"the mTOR-independent induction of autophagy reduced protein accumulation and restored neurite outgrowth in diseased OPTN(E50K) RGCs","explanation":"Reports the rescue that this readout measures.\n"}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:OPTN-related_Open_Angle_Glaucoma","model_node_id":"model:kb/disorders/OPTN-related_Open_Angle_Glaucoma.yaml:Isogenic OPTN(E50K) human pluripotent stem cell-derived retinal ganglion cells","focus_node_id":"node:disorder%3AOPTN-related_Open_Angle_Glaucoma:pathophysiology:Impaired%20Autophagic%20Flux%20in%20Retinal%20Ganglion%20Cells","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/OPTN-related_Open_Angle_Glaucoma.html#pathograph","nodes":[{"id":"model:kb/disorders/OPTN-related_Open_Angle_Glaucoma.yaml:Isogenic OPTN(E50K) human pluripotent stem cell-derived retinal ganglion cells","kind":"experimental_model","kind_label":"NAM model","label":"Isogenic OPTN(E50K) human pluripotent stem cell-derived retinal ganglion cells","description":"Human pluripotent stem cell lines in isogenic pairs - patient-derived iPSCs with the E50K mutation corrected, and an H7 embryonic line with E50K introduced by CRISPR/Cas9 - differentiated through retinal organoids into purified retinal ganglion cells. 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Mutant cells show impaired autophagic-lysosomal degradation, AMPK activation, reduced mTORC1 signalling and neurodegenerative features; mTOR-independent autophagy induction rescues neurite outgrowth.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/OPTN-related_Open_Angle_Glaucoma.html#experimental-model-isogenic-optn-e50k-human-pluripotent-stem-cell-derived-retinal-ganglion-cells","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AOPTN-related_Open_Angle_Glaucoma:pathophysiology:Impaired%20Autophagic%20Flux%20in%20Retinal%20Ganglion%20Cells","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Autophagic Flux in Retinal Ganglion Cells","description":"Optineurin is a selective autophagy receptor: it binds polyubiquitinated cargo through its ubiquitin-binding domain and delivers it to nascent autophagosomes through its LC3-interacting region, and it links autophagosomes to lysosomes via myosin VI. Retinal ganglion cells express optineurin highly and, as long-lived post-mitotic neurons with an exceptional axonal maintenance burden, depend heavily on autophagic quality control. Mutant optineurin blocks flux through this pathway. In OPTN(E50K) mice and in E50K-expressing retinal cells, LC3-II and p62/SQSTM1 both accumulate - the signature of a downstream block rather than reduced initiation - and undegraded substrates including TDP-43 aggregate in the cytoplasm. In isogenic OPTN(E50K) human stem cell-derived retinal ganglion cells the same lesion is accompanied by AMPK activation and reduced mTORC1 signalling, and mTOR-independent induction of autophagy restores neurite outgrowth, showing the block is the proximate cause of the neurodegenerative phenotype rather than a bystander. This node conforms to the `disabled_macroautophagy` module's central effector: the failure point here is selective cargo recognition by the receptor itself, not the core ATG machinery, and it is genetic rather than age-associated, but the resulting loss of cytoplasmic quality control is the conserved state that module models.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/OPTN-related_Open_Angle_Glaucoma.html#pathophysiology-impaired-autophagic-flux-in-retinal-ganglion-cells","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AOPTN-related_Open_Angle_Glaucoma:pathophysiology:Impaired%20Mitophagy%20and%20Mitochondrial%20Dysfunction","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Mitophagy and Mitochondrial Dysfunction","description":"Optineurin is one of the principal mitophagy receptors of the PINK1/Parkin pathway, and it initiates mitophagy by an unconventional route: rather than recruiting FIP200 and the ULK1/2 complex as NDP52, TAX1BP1 and p62 do, OPTN uses TBK1 bound directly to the class III PI3K complex I. Because that initiation step runs through the very kinase whose interaction E50K perturbs, the mitophagy arm is not simply a special case of the general autophagy block but a mechanistically distinct point of vulnerability. Failure to clear damaged mitochondria leaves retinal ganglion cells - among the most energetically demanding neurons in the body, with long unmyelinated intraretinal axons - carrying a dysfunctional mitochondrial pool. This node is curated as an amplifier of, not a substitute for, the autophagic-flux lesion.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/OPTN-related_Open_Angle_Glaucoma.html#pathophysiology-impaired-mitophagy-and-mitochondrial-dysfunction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AOPTN-related_Open_Angle_Glaucoma:pathophysiology:OPTN%20Missense%20Variant%20and%20Optineurin%20Misfolding","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"OPTN Missense Variant and Optineurin Misfolding","description":"A heterozygous missense change in OPTN - most commonly p.Glu50Lys (E50K), the recurrent allele in normal-tension glaucoma pedigrees - alters the biophysical behaviour of optineurin. Mutant OPTN binds TANK-binding kinase 1 (TBK1) abnormally strongly, which blocks the normal oligomerization and solubility that optineurin needs for its intracellular transitions, and the insoluble protein accumulates in the endoplasmic reticulum. Independently, E50K drives formation of covalently cross-linked optineurin oligomers of the kind normally seen only under oxidative stress. This is a toxic gain-of-function lesion rather than simple haploinsufficiency, which is why heterozygosity suffices and why TBK1 is a tractable drug target one step downstream.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/OPTN-related_Open_Angle_Glaucoma.html#pathophysiology-optn-missense-variant-and-optineurin-misfolding","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AOPTN-related_Open_Angle_Glaucoma:pathophysiology:Retinal%20Ganglion%20Cell%20Apoptosis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Retinal Ganglion Cell Apoptosis","description":"Retinal ganglion cells carrying mutant optineurin die by apoptosis. This is the node at which OPTN-related disease rejoins the conserved glaucomatous neurodegeneration captured by the `glaucoma_optic_neuropathy` module - but it is reached from a cell-autonomous proteostatic lesion rather than from the module's trabecular-outflow and elevated-IOP arm, which does not apply to this entity. E50K knock-in mice show reduced numbers of viable ganglion cells and raised cleaved caspase-3 in the retina at intraocular pressures indistinguishable from wild type, and E50K-overexpressing retinal cells show an increased early apoptotic fraction.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/OPTN-related_Open_Angle_Glaucoma.html#pathophysiology-retinal-ganglion-cell-apoptosis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/OPTN-related_Open_Angle_Glaucoma.yaml:Isogenic OPTN(E50K) human pluripotent stem cell-derived retinal ganglion cells","source_id":"model:kb/disorders/OPTN-related_Open_Angle_Glaucoma.yaml:Isogenic OPTN(E50K) human pluripotent stem cell-derived retinal ganglion 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stem cell-derived retinal ganglion cells associated with autophagy disruption and mTORC1 signaling reduction.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Taken together, these results highlighted that autophagy disruption resulted in increased autophagic demand which was associated with downregulated signaling through mTORC1, contributing to the degeneration of RGCs.","explanation":"The study's own conclusion that this human model demonstrates the autophagy-disruption node it is linked to.\n"},{"reference":"PMID:39425218","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39425218","reference_title":"Acquisition of neurodegenerative features in isogenic OPTN(E50K) human stem cell-derived retinal ganglion cells associated with autophagy disruption and mTORC1 signaling reduction.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We identified an impairment of autophagic-lysosomal degradation and decreased mTORC1 signaling via activation of the stress sensor AMPK, along with subsequent neurodegeneration in OPTN(E50K) RGCs differentiated from hPSCs","explanation":"Reports both measurements recorded in this readout.\n"},{"reference":"PMID:39425218","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39425218","reference_title":"Acquisition of neurodegenerative features in isogenic OPTN(E50K) human stem cell-derived retinal ganglion cells associated with autophagy disruption and mTORC1 signaling reduction.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"the mTOR-independent induction of autophagy reduced protein accumulation and restored neurite outgrowth in diseased OPTN(E50K) RGCs","explanation":"Reports the rescue that this readout measures.\n"}],"evidence_text":["we leveraged an isogenic hPSC model with a glaucoma-associated mutation in the Optineurin (OPTN) protein, which plays a prominent role in autophagy","Taken together, these results highlighted that autophagy disruption resulted in increased autophagic demand which was associated with downregulated signaling through mTORC1, contributing to the degeneration of RGCs.","We identified an impairment of autophagic-lysosomal degradation and decreased mTORC1 signaling via activation of the stress sensor AMPK, along with subsequent neurodegeneration in OPTN(E50K) RGCs differentiated from hPSCs","the mTOR-independent induction of autophagy reduced protein accumulation and restored neurite outgrowth in diseased OPTN(E50K) RGCs","Establishes the isogenic human stem-cell model described here.","The study's own conclusion that this human model demonstrates the autophagy-disruption node it is linked to.","Reports both measurements recorded in this readout.","Reports the rescue that this readout measures."],"evidence_status":"Evidence recorded","metadata_completeness":40,"metadata_present":["Model category","Cell type","Modeled mechanism","Evidence"],"metadata_missing":["NAMO class","Organism","Anatomy","Cell source","Culture 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The same system carries the unfolded-protein-response arm of this entry's second hypothesis group, and supplies its only pharmacological rescue.","notes":"Silencing any of the three UPR branches (IRE1, ATF6, PERK) worsened contractility in this system, which is why the UPR is curated here as protective rather than as the injury itself.","context_id":"disorder:Dilated_Cardiomyopathy_1P","context_kind":"Disorder","disease_name":"Dilated Cardiomyopathy 1P","disease_synonyms":["CMD1P","dilated cardiomyopathy type 1P","cardiomyopathy, dilated, 1P","PLN-related cardiomyopathy","phospholamban cardiomyopathy","familial isolated dilated cardiomyopathy caused by mutation in PLN"],"disease_term":{"id":"MONDO:0012362","label":"dilated cardiomyopathy 1P","display_label":"dilated cardiomyopathy 1P","url":"http://purl.obolibrary.org/obo/MONDO_0012362"},"experimental_model_type":"IPSC_DERIVED_MODEL","experimental_model_type_label":"iPSC-derived model","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},"organism_label":"Homo sapiens","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[{"id":"CL:0000746","label":"cardiac muscle cell","display_label":"hiPSC-derived cardiomyocyte","url":"http://purl.obolibrary.org/obo/CL_0000746"}],"model_cell_type_labels":["cardiac muscle cell"],"linked_cell_types":[{"id":"CL:0000746","label":"cardiac muscle cell","display_label":"ventricular cardiomyocyte","url":"http://purl.obolibrary.org/obo/CL_0000746"}],"linked_cell_type_labels":["cardiac muscle cell"],"cell_types":[{"id":"CL:0000746","label":"cardiac muscle cell","display_label":"hiPSC-derived cardiomyocyte","url":"http://purl.obolibrary.org/obo/CL_0000746"}],"cell_type_labels":["cardiac muscle cell"],"conditions":[],"cell_source":"Patient-derived hiPSC lines carrying PLN R14del, plus a healthy-donor line into which R14del was introduced; each paired with its CRISPR/Cas9-corrected or unedited isogenic control.","source_category":"Patient-derived","culture_system":"Two-dimensional monolayer culture and three-dimensional engineered heart tissue (3D-EHT).","publication":"PMID:33928785","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/33928785","mechanisms":[{"target":"Cardiomyocyte Contractile Dysfunction","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy_1P.html#pathophysiology-cardiomyocyte-contractile-dysfunction","relationship":"RECAPITULATES","relationship_label":"Recapitulates","fidelity":"MODERATE","fidelity_label":"Moderate","description":"R14del hiPSC-CMs show reduced contractility against their isogenic controls in both culture formats, which is the in-vitro counterpart of this node.","limitations":"hiPSC-CMs are immature relative to adult ventricular myocardium, lack the loading and neurohormonal environment of the intact heart, and cannot reproduce the chamber-level dilatation or the arrhythmic endpoints that dominate the human disease.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[{"id":"CL:0000746","label":"cardiac muscle cell","display_label":"ventricular cardiomyocyte","url":"http://purl.obolibrary.org/obo/CL_0000746"}],"biological_processes":[{"id":"GO:0055117","label":"regulation of cardiac muscle contraction","display_label":"regulation of cardiac muscle contraction","url":"http://purl.obolibrary.org/obo/GO_0055117"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Contractile force in 3D engineered heart tissue and 2D monolayer","description":null,"target":"Cardiomyocyte Contractile Dysfunction","direction":"DECREASED","interpretation":"Isogenic-paired contractility deficit, the quantifiable in-vitro correlate of the contractile-dysfunction node.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:33928785","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33928785","reference_title":"Unfolded Protein Response as a Compensatory Mechanism and Potential Therapeutic Target in PLN R14del Cardiomyopathy.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"hiPSC-CMs carrying the PLN R14del mutation (patient and HD R14del introduced) showed decreased contractility in three-dimensional engineered heart tissues (3D-EHTs)","explanation":"Reports the direction and the assay behind this readout."}],"notes":null}],"evidence":[{"reference":"PMID:33928785","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33928785","reference_title":"Unfolded Protein Response as a Compensatory Mechanism and Potential Therapeutic Target in PLN R14del Cardiomyopathy.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Modeling of the PLN R14del cardiomyopathy with isogenic pairs of hiPSC-CMs recapitulated the contractile deficit associated with the disease in vitro.","explanation":"States that this model is informative for the contractile-dysfunction node."},{"reference":"PMID:33928785","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33928785","reference_title":"Unfolded Protein Response as a Compensatory Mechanism and Potential Therapeutic Target in PLN R14del Cardiomyopathy.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"hiPSC-CMs carrying the PLN R14del mutation (patient and HD R14del introduced) showed decreased contractility in three-dimensional engineered heart tissues (3D-EHTs)","explanation":"Reports the direction and the assay behind this readout."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Dilated_Cardiomyopathy_1P","model_node_id":"model:kb/disorders/Dilated_Cardiomyopathy_1P.yaml:Isogenic PLN-R14del hiPSC-cardiomyocyte and 3D engineered heart tissue pair","focus_node_id":"node:disorder%3ADilated_Cardiomyopathy_1P:pathophysiology:Cardiomyocyte%20Contractile%20Dysfunction","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy_1P.html#pathograph","nodes":[{"id":"model:kb/disorders/Dilated_Cardiomyopathy_1P.yaml:Isogenic PLN-R14del hiPSC-cardiomyocyte and 3D engineered heart tissue pair","kind":"experimental_model","kind_label":"NAM model","label":"Isogenic PLN-R14del hiPSC-cardiomyocyte and 3D engineered heart tissue pair","description":"Three isogenic hiPSC pairs differing only at the PLN R14del allele, differentiated to cardiomyocytes and assayed for contractility in both 2D monolayers and 3D engineered heart tissues. 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dysfunction can also precede marked dilation.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1}]}}],"mechanism_names":["Reduced Ventricular Contractile Function"],"relationships":["Partially Recapitulates"],"fidelities":["Not Specified"],"biological_scales":["Organism"],"system_context_sources":["Linked mechanism anatomy","Linked mechanism biological scale"],"modeled_system_labels":["heart","Organism"],"biological_process_terms":[],"biological_processes":[],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":["Isolated cardiomyocyte contractility"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:30987448","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30987448","reference_title":"Genetic Variants Associated With Cancer Therapy-Induced Cardiomyopathy.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Cardiomyocytes from doxorubicin-treated Ttntv/+ mice had significantly depressed contractility","explanation":"Ex-vivo cellular mechanics corroborate persistent functional impairment."}],"evidence_text":["Cardiomyocytes from doxorubicin-treated Ttntv/+ mice had significantly depressed contractility","Ex-vivo cellular mechanics corroborate persistent functional impairment."],"evidence_status":"Evidence recorded","metadata_completeness":40,"metadata_present":["Model category","Anatomy","Modeled mechanism","Evidence"],"metadata_missing":["NAMO class","Organism","Cell type","Cell source","Culture system","Publication"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Anthracycline_Induced_Cardiomyopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Anthracycline_Induced_Cardiomyopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Anthracycline-Induced_Cardiomyopathy.html#experimental-model-isolated-titin-truncation-mouse-cardiomyocyte-mechanics","source_anchor":"experimental-model-isolated-titin-truncation-mouse-cardiomyocyte-mechanics"},{"id":"model:kb/disorders/LDLR-Related_Familial_Hypercholesterolemia.yaml:J.D. fibroblast strain (internalization-defective LDLR alleles)","name":"J.D. fibroblast strain (internalization-defective LDLR alleles)","description":"Cultured skin fibroblasts from subject J.D., one of 22 fibroblast strains from patients with the clinical phenotype of homozygous FH screened by Brown and Goldstein. This is the system in which the receptor mutation classes were defined: the other 21 strains bound labelled LDL either not at all (receptor-negative) or poorly (receptor-defective), while J.D. bound LDL normally and failed to internalize it, which is the observation that established internalization as a separable step and gave the entry its Class 4 allele.\nJ.D. is a compound heterozygote, not a true homozygote: a maternal exon 13-15 deletion producing no functional protein, and a paternal Y807C allele producing a receptor that reaches the surface and binds LDL. The 1976 designation is a pre-molecular clinical label. The cellular phenotype is nonetheless cleanly internalization-defective, because the only receptor these cells display is the Y807C one.","notes":null,"context_id":"disorder:LDLR-Related_Familial_Hypercholesterolemia","context_kind":"Disorder","disease_name":"LDLR-Related Familial Hypercholesterolemia","disease_synonyms":["Hypercholesterolemia, familial, 1","FHCL1","Familial hypercholesterolemia type 1","LDL receptor disorder","LDL receptor deficiency","Hyperlipoproteinemia type 2A","Familial hypercholesterolemic xanthomatosis","Autosomal dominant hypercholesterolemia 1"],"disease_term":{"id":"MONDO:0007750","label":"hypercholesterolemia, familial, 1","display_label":"LDLR-Related Familial Hypercholesterolemia","url":"http://purl.obolibrary.org/obo/MONDO_0007750"},"experimental_model_type":"PRIMARY_CELL_CULTURE","experimental_model_type_label":"Primary-cell culture","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},"organism_label":"Homo sapiens","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[{"id":"CL:0002620","label":"skin fibroblast","display_label":"skin fibroblast","url":"http://purl.obolibrary.org/obo/CL_0002620"}],"model_cell_type_labels":["skin fibroblast"],"linked_cell_types":[{"id":"CL:0000182","label":"hepatocyte","display_label":"hepatocyte","url":"http://purl.obolibrary.org/obo/CL_0000182"}],"linked_cell_type_labels":["hepatocyte"],"cell_types":[{"id":"CL:0002620","label":"skin fibroblast","display_label":"skin fibroblast","url":"http://purl.obolibrary.org/obo/CL_0002620"},{"id":"CL:0000182","label":"hepatocyte","display_label":"hepatocyte","url":"http://purl.obolibrary.org/obo/CL_0000182"}],"cell_type_labels":["skin fibroblast","hepatocyte"],"conditions":[],"cell_source":"Patient-derived skin fibroblasts (homozygous FH probands)","source_category":"Patient-derived","culture_system":"Two-dimensional monolayer fibroblast culture","publication":"PMID:189940","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/189940","mechanisms":[{"target":"Defective Clustering in Clathrin-Coated Pits","target_url":"https://dismech.monarchinitiative.org/pages/disorders/LDLR-Related_Familial_Hypercholesterolemia.html#pathophysiology-defective-clustering-in-clathrin-coated-pits","relationship":"RECAPITULATES","relationship_label":"Recapitulates","fidelity":"HIGH","fidelity_label":"High","description":"The founding measurement of this node. Binding and internalization are assayed separately in the same cells, so the defect is localized to the internalization step rather than inferred from a lowered uptake total.","limitations":"Fibroblasts are not hepatocytes, and hepatic receptor activity is what sets plasma LDL; the strain establishes that the step exists and can be broken in isolation, not the quantitative hepatic consequence. The 1976 report also predates identification of the underlying LDLR sequence changes, so what it measures is the cellular phenotype and not the alleles, and the compound-heterozygous genotype means the strain reports the Y807C allele in the absence of a second functional receptor rather than a Class 4 allele in isolation.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[{"id":"CL:0000182","label":"hepatocyte","display_label":"hepatocyte","url":"http://purl.obolibrary.org/obo/CL_0000182"}],"biological_processes":[{"id":"GO:0072583","label":"clathrin-dependent endocytosis","display_label":"clathrin-dependent endocytosis","url":"http://purl.obolibrary.org/obo/GO_0072583"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Internalization of receptor-bound 125I-LDL","description":null,"target":"Defective Clustering in Clathrin-Coated Pits","direction":"DECREASED","interpretation":"Normal high-affinity binding alongside a profound internalization defect in the same cells is the direct measurement this node asserts. The 1976 assay recorded no detectable internalization; DECREASED rather than ABOLISHED is used because the expression-cloning work this entry also cites (PMID:3955657) later showed the Y807C receptor enters the cell slowly rather than not at all.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:189940","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/189940","reference_title":"Analysis of a mutant strain of human fibroblasts with a defect in the internalization of receptor-bound low density lipoprotein.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"the cell surface receptor for plasma low density lipoprotein (LDL) was able to bind 125I-labeled LDL normally, but internalization of the receptor-bound lipoprotein failed to occur","explanation":"Reports the paired binding and internalization measurements grounding this readout."}],"notes":null}],"evidence":[{"reference":"PMID:189940","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/189940","reference_title":"Analysis of a mutant strain of human fibroblasts with a defect in the internalization of receptor-bound low density lipoprotein.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"the defect in this strain differed from the defects found in the fibroblasts from the other 21 FH homozygote strains in which the binding of 125I-LDL to the receptor was either absent (receptor-negative) or markedly reduced (receptor-defective)","explanation":"Establishes the contrast against the receptor-negative and receptor-defective strains, which is what makes this strain informative for internalization specifically rather than for receptor loss in general."},{"reference":"PMID:189940","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/189940","reference_title":"Analysis of a mutant strain of human fibroblasts with a defect in the internalization of receptor-bound low density lipoprotein.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"the cell surface receptor for plasma low density lipoprotein (LDL) was able to bind 125I-labeled LDL normally, but internalization of the receptor-bound lipoprotein failed to occur","explanation":"Reports the paired binding and internalization measurements grounding this readout."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:LDLR-Related_Familial_Hypercholesterolemia","model_node_id":"model:kb/disorders/LDLR-Related_Familial_Hypercholesterolemia.yaml:J.D. fibroblast strain (internalization-defective LDLR alleles)","focus_node_id":"node:disorder%3ALDLR-Related_Familial_Hypercholesterolemia:pathophysiology:Defective%20Clustering%20in%20Clathrin-Coated%20Pits","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/LDLR-Related_Familial_Hypercholesterolemia.html#pathograph","nodes":[{"id":"model:kb/disorders/LDLR-Related_Familial_Hypercholesterolemia.yaml:J.D. fibroblast strain (internalization-defective LDLR alleles)","kind":"experimental_model","kind_label":"NAM model","label":"J.D. fibroblast strain (internalization-defective LDLR alleles)","description":"Cultured skin fibroblasts from subject J.D., one of 22 fibroblast strains from patients with the clinical phenotype of homozygous FH screened by Brown and Goldstein. 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The cellular phenotype is nonetheless cleanly internalization-defective, because the only receptor these cells display is the Y807C one.","url":"https://dismech.monarchinitiative.org/pages/disorders/LDLR-Related_Familial_Hypercholesterolemia.html#experimental-model-j-d-fibroblast-strain-internalization-defective-ldlr-alleles","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALDLR-Related_Familial_Hypercholesterolemia:pathophysiology:Defective%20Clustering%20in%20Clathrin-Coated%20Pits","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Defective Clustering in Clathrin-Coated Pits","description":"The class 4 (internalization-defective) branch. 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Because the LDLRAP1/ARH adaptor serves this same step, the recessive LDLRAP1 disease is the phenocopy of this branch acting in trans.","url":"https://dismech.monarchinitiative.org/pages/disorders/LDLR-Related_Familial_Hypercholesterolemia.html#pathophysiology-defective-clustering-in-clathrin-coated-pits","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALDLR-Related_Familial_Hypercholesterolemia:pathophysiology:LDLR%20Loss-of-Function%20Variant","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"LDLR Loss-of-Function Variant","description":"A germline pathogenic variant in LDLR at 19p13.2. 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This node is the single lesion; the five nodes immediately downstream are the alternative steps at which it can act.","url":"https://dismech.monarchinitiative.org/pages/disorders/LDLR-Related_Familial_Hypercholesterolemia.html#pathophysiology-ldlr-loss-of-function-variant","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALDLR-Related_Familial_Hypercholesterolemia:pathophysiology:Reduced%20Functional%20Hepatic%20LDL%20Receptor%20Activity","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced Functional Hepatic LDL Receptor Activity","description":"The convergence node of the allelic series. Whichever step is broken - synthesis, ER export, ligand binding, internalization, or recycling - the measurable output is the same: fewer LDL particles cleared per unit time by the hepatocyte. Functional assays report this as a single quantity (percentage of wild-type LDL uptake), which is why class assignment and residual activity are recorded separately: the class says *where* the itinerary breaks, the residual activity says *how much* capacity survives. Null alleles are conventionally under about 2% of normal activity, though trial protocols have operationalized \"null\" at thresholds as high as 15%.","url":"https://dismech.monarchinitiative.org/pages/disorders/LDLR-Related_Familial_Hypercholesterolemia.html#pathophysiology-reduced-functional-hepatic-ldl-receptor-activity","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/LDLR-Related_Familial_Hypercholesterolemia.yaml:J.D. fibroblast strain (internalization-defective LDLR alleles)","source_id":"model:kb/disorders/LDLR-Related_Familial_Hypercholesterolemia.yaml:J.D. fibroblast strain (internalization-defective LDLR alleles)","target_id":"node:disorder%3ALDLR-Related_Familial_Hypercholesterolemia:pathophysiology:Defective%20Clustering%20in%20Clathrin-Coated%20Pits","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"HIGH","causal_link_type":null,"causal_link_type_label":null,"description":"The founding measurement of this node. 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125I-LDL"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:189940","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/189940","reference_title":"Analysis of a mutant strain of human fibroblasts with a defect in the internalization of receptor-bound low density lipoprotein.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"the defect in this strain differed from the defects found in the fibroblasts from the other 21 FH homozygote strains in which the binding of 125I-LDL to the receptor was either absent (receptor-negative) or markedly reduced (receptor-defective)","explanation":"Establishes the contrast against the receptor-negative and receptor-defective strains, which is what makes this strain informative for internalization specifically rather than for receptor loss in 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Whether statins behave the same way in receptor-negative disease has not been tested here - the two null patients in that trial were already on stable statin therapy at enrolment - and the mechanisms differ (statins act transcriptionally on receptor synthesis, PCSK9-directed agents post-translationally on receptor degradation and recycling), so the statin/PCSK9 asymmetry is carried as an open question in the residual_ldlr_activity_response_threshold discussion rather than asserted. LDLR-independent agents - the MTP inhibitor lomitapide, the ANGPTL3 antibody evinacumab, and lipoprotein apheresis - bypass the receptor entirely and retain effect in null-null disease. 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Null alleles are conventionally under about 2% of normal activity, though trial protocols have operationalized \"null\" at thresholds as high as 15%.","url":"https://dismech.monarchinitiative.org/pages/disorders/LDLR-Related_Familial_Hypercholesterolemia.html#pathophysiology-reduced-functional-hepatic-ldl-receptor-activity","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:1:model:kb/disorders/LDLR-Related_Familial_Hypercholesterolemia.yaml:JD iPSC-derived hepatocyte-like cells","source_id":"model:kb/disorders/LDLR-Related_Familial_Hypercholesterolemia.yaml:JD iPSC-derived hepatocyte-like cells","target_id":"node:disorder%3ALDLR-Related_Familial_Hypercholesterolemia:pathophysiology:Residual%20Receptor%20Activity%20Gates%20Receptor-Dependent%20LDL%20Lowering","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[1]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"Control hepatocyte-like cells raise LDL uptake when given lovastatin and the FH cells do not. 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This entry models the receptor defect as impaired clearance only, and that is a deliberate scope limit rather than a claim that clearance is the whole mechanism - the authors argue explicitly that hepatic apoB-lipoprotein overproduction contributes too. No pathophysiology node is asserted for it here because the human evidence for an LDLR-specific overproduction arm was not assessed in this curation round.","evidence":[{"reference":"PMID:22653811","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/22653811","reference_title":"JD induced pluripotent stem cell-derived hepatocytes faithfully recapitulate the pathophysiology of familial hypercholesterolemia.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"FH iPSC-derived hepatocytes display a marked elevation in secretion of lipidated apolipoprotein B-100","explanation":"Reports the oversecretion result. Recorded as a finding rather than as a mechanism node so that the gap between this model's output and the entry's clearance-only pathograph is visible rather than silent."}]}],"findings_text":["The same model reports a second, non-clearance abnormality: FH hepatocyte-like cells oversecrete lipidated apolipoprotein B-100 roughly eight-fold over controls. This entry models the receptor defect as impaired clearance only, and that is a deliberate scope limit rather than a claim that clearance is the whole mechanism - the authors argue explicitly that hepatic apoB-lipoprotein overproduction contributes too. 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Recorded as a finding rather than as a mechanism node so that the gap between this model's output and the entry's clearance-only pathograph is visible rather than silent."}],"evidence_text":["we produced iPSCs from JD a patient with mutations in the low-density lipoprotein receptor (LDLR) gene that result in familial hypercholesterolemia (FH)","in contrast to control cells, FH iPSC-derived hepatocytes are deficient in LDL-C uptake","these findings demonstrate that FH iPSC-derived hepatocytes recapitulate the complex pathophysiology of FH in culture","control but not FH iPSC-derived hepatocytes increase LDL uptake in response to lovastatin","the extent of induction was similar regardless of genotype","FH iPSC-derived hepatocytes display a marked elevation in secretion of lipidated apolipoprotein B-100","Establishes that the line carries a patient LDLR genotype, which is what makes its uptake behaviour informative for this node.","Reports the uptake deficit grounding this readout.","The authors' own summary claim that the model reproduces FH hepatocyte behaviour, which is the basis for treating it as informative here.","Reports the differential statin response grounding this readout.","Locates the block. 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In a subset of patients the disease progresses beyond hypertrophy to systolic failure with normal or only mildly enlarged diastolic dimensions - an end-stage picture that is not typical burnt-out HCM and was one reason the Finnish cohort was described as atypical.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_17.html#pathophysiology-prohypertrophic-cardiomyocyte-remodeling","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:1:model:kb/disorders/Hypertrophic_Cardiomyopathy_17.yaml:JPH2 p.(Thr161Lys) patient-derived iPSC cardiomyocytes","source_id":"model:kb/disorders/Hypertrophic_Cardiomyopathy_17.yaml:JPH2 p.(Thr161Lys) patient-derived iPSC cardiomyocytes","target_id":"node:disorder%3AHypertrophic_Cardiomyopathy_17:pathophysiology:Disordered%20Intracellular%20Calcium%20Handling","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[1]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"The mutant cardiomyocytes show prolonged action potential duration and increased arrhythmogenicity, attributed to slower inactivation of calcium channels - a calcium-handling abnormality in a human cell carrying the disease allele.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AHypertrophic_Cardiomyopathy_17:2:1","source_id":"node:disorder%3AHypertrophic_Cardiomyopathy_17:pathophysiology:Disordered%20Intracellular%20Calcium%20Handling","target_id":"node:disorder%3AHypertrophic_Cardiomyopathy_17:phenotype:Arrhythmia","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[1]","label":"Indirectly causes (known intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_KNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Known Intermediates","description":"Disordered calcium release is the substrate for the arrhythmic vulnerability and conduction disease seen in carriers, and the steps between the two are identified rather than assumed. Spontaneous sarcoplasmic reticulum calcium release appears as cell-wide calcium waves; these activate the sodium-calcium exchanger, which generates delayed afterdepolarizations, and the resulting triggered activity is the arrhythmia. This was worked out for the E169K allele, found in hypertrophic cardiomyopathy patients with juvenile-onset paroxysmal atrial fibrillation and modelled in pseudoknock-in mice.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":4},{"id":"causal:disorder%3AHypertrophic_Cardiomyopathy_17:2:0","source_id":"node:disorder%3AHypertrophic_Cardiomyopathy_17:pathophysiology:Disordered%20Intracellular%20Calcium%20Handling","target_id":"node:disorder%3AHypertrophic_Cardiomyopathy_17:pathophysiology:Prohypertrophic%20Cardiomyocyte%20Remodeling","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Altered calcium handling engages the hypertrophic signalling programme in the cardiomyocyte.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AHypertrophic_Cardiomyopathy_17:1:0","source_id":"node:disorder%3AHypertrophic_Cardiomyopathy_17:pathophysiology:Dyad%20Disruption%20and%20Uncoupling%20of%20the%20L-Type%20Channel%20from%20the%20Ryanodine%20Receptor","target_id":"node:disorder%3AHypertrophic_Cardiomyopathy_17:pathophysiology:Disordered%20Intracellular%20Calcium%20Handling","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"An untriggered or weakly triggered release produces an abnormal calcium transient.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1}]}}],"mechanism_names":["Prohypertrophic Cardiomyocyte Remodeling","Disordered Intracellular Calcium Handling"],"relationships":["Recapitulates"],"fidelities":["Moderate"],"biological_scales":["Tissue","Cellular"],"system_context_sources":["Model-level cell type","Linked mechanism anatomy","Linked mechanism cell type","Linked mechanism biological scale"],"modeled_system_labels":["myocardium","cardiac muscle cell","Tissue","Cellular"],"biological_process_terms":[{"id":"GO:0014898","label":"cardiac muscle hypertrophy in response to stress","display_label":"Cardiac muscle hypertrophy in response to stress","url":"http://purl.obolibrary.org/obo/GO_0014898"},{"id":"GO:0006874","label":"intracellular calcium ion homeostasis","display_label":"Intracellular calcium ion homeostasis","url":"http://purl.obolibrary.org/obo/GO_0006874"},{"id":"GO:0010882","label":"regulation of cardiac muscle contraction by calcium ion signaling","display_label":"Regulation of cardiac muscle contraction by calcium ion signaling","url":"http://purl.obolibrary.org/obo/GO_0010882"}],"biological_processes":["cardiac muscle hypertrophy in response to stress","intracellular calcium ion homeostasis","regulation of cardiac muscle contraction by calcium ion signaling"],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":["Cellular hypertrophy, multi-nucleation and sarcomeric disarray","Action potential duration and arrhythmogenicity"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:37371654","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/37371654","reference_title":"The Junctophilin-2 Mutation p.(Thr161Lys) Is Associated with Hypertrophic Cardiomyopathy Using Patient-Specific iPS Cardiomyocytes and Demonstrates Prolonged Action Potential and Increased Arrhythmogenicity.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"JPH2-hiPSC-CMs displayed key HCM hallmarks (cellular hypertrophy, multi-nucleation, sarcomeric disarray).","explanation":"Supports treating this line as informative for the hypertrophic remodeling node."},{"reference":"PMID:37371654","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/37371654","reference_title":"The Junctophilin-2 Mutation p.(Thr161Lys) Is Associated with Hypertrophic Cardiomyopathy Using Patient-Specific iPS Cardiomyocytes and Demonstrates Prolonged Action Potential and Increased Arrhythmogenicity.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Functional evaluation supported clinical observations, with differences in beating characteristics when compared with isogenic-hiPSC-CMs.","explanation":"The isogenic comparison supports attributing the functional differences to the variant."},{"reference":"PMID:37371654","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/37371654","reference_title":"The Junctophilin-2 Mutation p.(Thr161Lys) Is Associated with Hypertrophic Cardiomyopathy Using Patient-Specific iPS Cardiomyocytes and Demonstrates Prolonged Action Potential and Increased Arrhythmogenicity.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"JPH2-hiPSC-CMs exhibit a higher degree of arrhythmia and longer action potential duration associated with slower inactivation of calcium channels","explanation":"Reports the electrophysiological and calcium-handling abnormality measured in the patient-derived line."}],"evidence_text":["JPH2-hiPSC-CMs displayed key HCM hallmarks (cellular hypertrophy, multi-nucleation, sarcomeric disarray).","Functional evaluation supported clinical observations, with differences in beating characteristics when compared with isogenic-hiPSC-CMs.","JPH2-hiPSC-CMs exhibit a higher degree of arrhythmia and longer action potential duration associated with slower inactivation of calcium channels","Supports treating this line as informative for the hypertrophic remodeling node.","The isogenic comparison supports attributing the functional differences to the variant.","Reports the electrophysiological and calcium-handling abnormality measured in the patient-derived line."],"evidence_status":"Evidence recorded","metadata_completeness":70,"metadata_present":["Model category","Organism","Anatomy","Cell type","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Cell source","Culture system"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Hypertrophic_Cardiomyopathy_17.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hypertrophic_Cardiomyopathy_17.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_17.html#experimental-model-jph2-p-thr161lys-patient-derived-ipsc-cardiomyocytes","source_anchor":"experimental-model-jph2-p-thr161lys-patient-derived-ipsc-cardiomyocytes"},{"id":"model:kb/disorders/CASQ2_CPVT.yaml:K180R Isogenic Corrected iPSC Resource","name":"K180R Isogenic Corrected iPSC Resource","description":"A CRISPR-corrected control line, CIAUi003-A-1, complements the parental heterozygous K180R line. The resource paper reports genetic correction, not rescue of a cardiac electrophysiological phenotype.","notes":"No RESCUES mechanism link is assigned because functional rescue was not reported.","context_id":"disorder:CASQ2_CPVT","context_kind":"Disorder","disease_name":"CASQ2 CPVT","disease_synonyms":["CPVT2","catecholaminergic polymorphic ventricular tachycardia 2","CASQ2 catecholaminergic polymorphic ventricular tachycardia","catecholaminergic polymorphic ventricular tachycardia caused by mutation in CASQ2","ventricular tachycardia, catecholaminergic polymorphic, 2"],"disease_term":{"id":"MONDO:0012762","label":"catecholaminergic polymorphic ventricular tachycardia 2","display_label":"catecholaminergic polymorphic ventricular tachycardia 2","url":"http://purl.obolibrary.org/obo/MONDO_0012762"},"experimental_model_type":"IPSC_DERIVED_MODEL","experimental_model_type_label":"iPSC-derived model","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":"CIAUi003-A patient line and CRISPR-corrected isogenic control","source_category":"Patient-derived","culture_system":null,"publication":"PMID:39826349","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39826349","mechanisms":[],"mechanism_names":[],"relationships":[],"fidelities":[],"biological_scales":[],"system_context_sources":[],"modeled_system_labels":[],"biological_process_terms":[],"biological_processes":[],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":[],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:39826349","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39826349","reference_title":"Generation of an isogenic CRISPR/Cas9-corrected control induced pluripotent stem cell line from a patient with autosomal dominant catecholaminergic polymorphic ventricular tachycardia with a heterozygous variant in cardiac calsequestrin-2.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"creating a CRISPR-corrected isogenic control line (CIAUi003-A-1)","explanation":"Documents availability of the isogenic resource without claiming functional rescue."}],"evidence_text":["creating a CRISPR-corrected isogenic control line (CIAUi003-A-1)","Documents availability of the isogenic resource without claiming functional rescue."],"evidence_status":"Evidence recorded","metadata_completeness":40,"metadata_present":["Model category","Cell source","Publication","Evidence"],"metadata_missing":["NAMO class","Organism","Anatomy","Cell type","Culture system","Modeled mechanism"],"dataset_context":"Available in same entry","context_dataset_ids":["dataset:bioproject:prjna623119","dataset:bioproject:prjna916203"],"candidate_dataset_ids":[],"source_path":"kb/disorders/CASQ2_CPVT.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/CASQ2_CPVT.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/CASQ2_CPVT.html#experimental-model-k180r-isogenic-corrected-ipsc-resource","source_anchor":"experimental-model-k180r-isogenic-corrected-ipsc-resource"},{"id":"model:kb/disorders/CPLX1-Related_DEE.yaml:KAIMRCi003A and KAIMRCi003B patient iPSCs","name":"KAIMRCi003A and KAIMRCi003B patient iPSCs","description":"Two integration-free iPSC clones were generated from one seven-year-old patient labelled with Dravet syndrome, developmental delay, infantile seizures and choreoathetotic movements. Both carry homozygous CPLX1 p.Glu2Lys and a heterozygous SCN9A in-frame deletion. Identity, normal female karyotype, pluripotency and trilineage differentiation were characterized. Disease-relevant neuronal physiology, isogenic correction and functional rescue were proposed future work, not reported results.","notes":"An undifferentiated patient-derived resource, not yet a validated neuronal disease model. The co-occurring SCN9A variant prevents assigning cellular findings to CPLX1 without further experiments.","context_id":"disorder:CPLX1-Related_DEE","context_kind":"Disorder","disease_name":"CPLX1-Related Developmental and Epileptic Encephalopathy","disease_synonyms":["Developmental and epileptic encephalopathy 63","DEE63","Early infantile epileptic encephalopathy 63","EIEE63"],"disease_term":{"id":"MONDO:0033372","label":"developmental and epileptic encephalopathy, 63","display_label":"CPLX1 developmental and epileptic encephalopathy","url":"http://purl.obolibrary.org/obo/MONDO_0033372"},"experimental_model_type":"OTHER","experimental_model_type_label":"Other","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":"Patient peripheral blood erythroid progenitors reprogrammed to iPSCs","source_category":"Patient-derived","culture_system":null,"publication":null,"publication_url":null,"mechanisms":[],"mechanism_names":[],"relationships":[],"fidelities":[],"biological_scales":[],"system_context_sources":[],"modeled_system_labels":[],"biological_process_terms":[],"biological_processes":[],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":[],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"DOI:10.1007/s13577-023-01016-z","reference_url":null,"reference_title":"Generation of iPSC lines (KAIMRCi003A, KAIMRCi003B) from a Saudi patient with Dravet syndrome carrying homozygous mutation in the CPLX1 gene and heterozygous mutation in SCN9A","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Here, we established two DRVT-iPSC lines harboring a homozygous mutation in the CPLX1 gene and heterozygous mutation in SCN9A gene.","explanation":"Two iPSC clones were derived from one donor carrying both variants; this is a resource-generation result."},{"reference":"DOI:10.1007/s13577-023-01016-z","reference_url":null,"reference_title":"Generation of iPSC lines (KAIMRCi003A, KAIMRCi003B) from a Saudi patient with Dravet syndrome carrying homozygous mutation in the CPLX1 gene and heterozygous mutation in SCN9A","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"Further analysis unraveled homozygous variant c.4G > A p.(Glu2Lys) in the CPLX1 gene. This variant leads to an amino acid exchange in exon 1 (NM_006651.4).","explanation":"The donor carried homozygous p.Glu2Lys as well as a heterozygous SCN9A deletion; this establishes the genotype, not single-gene causation."}],"evidence_text":["Here, we established two DRVT-iPSC lines harboring a homozygous mutation in the CPLX1 gene and heterozygous mutation in SCN9A gene.","Further analysis unraveled homozygous variant c.4G > A p.(Glu2Lys) in the CPLX1 gene. This variant leads to an amino acid exchange in exon 1 (NM_006651.4).","Two iPSC clones were derived from one donor carrying both variants; this is a resource-generation result.","The donor carried homozygous p.Glu2Lys as well as a heterozygous SCN9A deletion; this establishes the genotype, not single-gene causation."],"evidence_status":"Evidence recorded","metadata_completeness":30,"metadata_present":["Model category","Cell source","Evidence"],"metadata_missing":["NAMO class","Organism","Anatomy","Cell type","Culture system","Modeled mechanism","Publication"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/CPLX1-Related_DEE.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/CPLX1-Related_DEE.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/CPLX1-Related_Developmental_and_Epileptic_Encephalopathy.html#experimental-model-kaimrci003a-and-kaimrci003b-patient-ipscs","source_anchor":"experimental-model-kaimrci003a-and-kaimrci003b-patient-ipscs"},{"id":"model:kb/disorders/Biotin_Thiamine_Responsive_Basal_Ganglia_Disease.yaml:KAIMRCi004-A/B patient-derived BTBGD iPSC neural progenitor model","name":"KAIMRCi004-A/B patient-derived BTBGD iPSC neural progenitor model","description":"Two patient-derived iPSC clones carrying homozygous SLC19A3 c.1264A>G (p.Thr422Ala) were validated for pluripotency and differentiated into neural progenitors. The lines provide a genetically relevant human neural resource, but the publication did not yet demonstrate a disease-specific transport, metabolic, or injury phenotype.","notes":null,"context_id":"disorder:Biotin_Thiamine_Responsive_Basal_Ganglia_Disease","context_kind":"Disorder","disease_name":"Biotin-Thiamine-Responsive Basal Ganglia Disease","disease_synonyms":["BBGD","BTBGD","BTRBGD","Biotin-responsive basal ganglia disease","Thiamine-responsive encephalopathy","Thiamine metabolism dysfunction syndrome 2"],"disease_term":{"id":"MONDO:0011841","label":"biotin-responsive basal ganglia disease","display_label":"biotin-thiamine-responsive basal ganglia disease","url":"http://purl.obolibrary.org/obo/MONDO_0011841"},"experimental_model_type":"IPSC_DERIVED_MODEL","experimental_model_type_label":"iPSC-derived model","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},"organism_label":"Homo sapiens","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":["Homozygous SLC19A3 c.1264A>G (p.Thr422Ala)","Unedited patient-derived iPSC clones differentiated to neural progenitors"],"cell_source":"Peripheral-blood-mononuclear-cell-derived iPSC clones from a 10-year-old female with BTBGD","source_category":"iPSC-derived","culture_system":"iPSC monolayer culture followed by differentiation to central-nervous-system neural progenitors","publication":"PMID:38980565","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38980565","mechanisms":[],"mechanism_names":[],"relationships":[],"fidelities":[],"biological_scales":[],"system_context_sources":[],"modeled_system_labels":[],"biological_process_terms":[],"biological_processes":[],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":[],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:38980565","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38980565","reference_title":"Derivation of two iPSC lines (KAIMRCi004-A, KAIMRCi004-B) from a Saudi patient with Biotin-Thiamine-responsive Basal Ganglia Disease (BTBGD) carrying homozygous pathogenic missense variant in the SCL19A3 gene.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"we have generated two clones of induced pluripotent stem cells (iPSCs) from a 10-year-old female BTBGD patient carrying a homozygous mutation for the pathogenic variant in exon 5 of the SLC19A3 gene, c.1264A > G (p.Thr422Ala).","explanation":"The report directly identifies the patient source, two clones, and causal genotype."},{"reference":"PMID:38980565","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38980565","reference_title":"Derivation of two iPSC lines (KAIMRCi004-A, KAIMRCi004-B) from a Saudi patient with Biotin-Thiamine-responsive Basal Ganglia Disease (BTBGD) carrying homozygous pathogenic missense variant in the SCL19A3 gene.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We have confirmed the pluripotency of the generated iPS lines and successfully differentiated them to neural progenitors.","explanation":"The publication directly validates pluripotency and neural-progenitor differentiation."}],"evidence_text":["we have generated two clones of induced pluripotent stem cells (iPSCs) from a 10-year-old female BTBGD patient carrying a homozygous mutation for the pathogenic variant in exon 5 of the SLC19A3 gene, c.1264A > G (p.Thr422Ala).","We have confirmed the pluripotency of the generated iPS lines and successfully differentiated them to neural progenitors.","The report directly identifies the patient source, two clones, and causal genotype.","The publication directly validates pluripotency and neural-progenitor differentiation."],"evidence_status":"Evidence recorded","metadata_completeness":60,"metadata_present":["Model category","Organism","Cell source","Culture system","Publication","Evidence"],"metadata_missing":["NAMO class","Anatomy","Cell type","Modeled mechanism"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Biotin_Thiamine_Responsive_Basal_Ganglia_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Biotin_Thiamine_Responsive_Basal_Ganglia_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Biotin-Thiamine-Responsive_Basal_Ganglia_Disease.html#experimental-model-kaimrci004-a-b-patient-derived-btbgd-ipsc-neural-progenitor-model","source_anchor":"experimental-model-kaimrci004-a-b-patient-derived-btbgd-ipsc-neural-progenitor-model"},{"id":"model:kb/disorders/BBSome-Related_Retinitis_Pigmentosa.yaml:KCi001-A BBS1 patient-derived induced pluripotent stem cell line","name":"KCi001-A BBS1 patient-derived induced pluripotent stem cell line","description":"A patient-derived pluripotent resource carrying BBS1 p.Met390Arg and p.Gly370Arg. The donor had Bardet-Biedl syndrome rather than confirmed isolated RP, and the undifferentiated line is a platform for downstream retinal differentiation rather than a validated retinal phenotype model.","notes":"Not linked to a pathograph node: the cited report characterises pluripotency only and reports no retinal differentiation or BBSome readout, so there is no mechanism claim for a modeled_mechanisms link to carry. Linking it would assert a model result that has not been published.","context_id":"disorder:BBSome-Related_Retinitis_Pigmentosa","context_kind":"Disorder","disease_name":"BBSome-related retinitis pigmentosa","disease_synonyms":["BBSome-machine nonsyndromic retinitis pigmentosa","BBSome-associated isolated retinal dystrophy","BBSome-related rod-cone dystrophy"],"disease_term":{"id":null,"label":"BBSome-related retinitis pigmentosa","display_label":"BBSome-related retinitis pigmentosa","url":null},"experimental_model_type":"CELL_LINE","experimental_model_type_label":"Cell line","namo_type":"namo:CellLineModel","declared_namo_class_name":null,"namo_class_name":"CellLineModel","namo_class_label":"Cell Line Model","namo_description":"A model system based on immortalized cell lines that can be maintained in culture indefinitely. 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These results support gene function but are not direct measurements in skeletal-patient growth plates.","url":"https://dismech.monarchinitiative.org/pages/disorders/Short-rib_thoracic_dysplasia_21_without_polydactyly.html#pathophysiology-impaired-hedgehog-signal-transduction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AShort-rib_Thoracic_Dysplasia_21_Without_Polydactyly:pathophysiology:Defective%20Basal%20Body%20Docking%20and%20Ciliogenesis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Defective Basal Body Docking and Ciliogenesis","description":"KIAA0753 forms a ternary complex with OFD1 and FOPNL (FOR20) at centrosomes and pericentriolar satellites, and it acts upstream of them: mammalian centrioles need Moonraker to recruit OFD1, FOPNL and CEP90, which then place the distal appendage proteins CEP83, CEP89 and CEP164. 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This is the functional consequence of a defective small subunit and the step at which a single ribosomal-protein defect becomes a multi-complex disease: the mitoribosome makes only thirteen proteins, but they are distributed across complexes I, III, IV and V.","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Oxidative_Phosphorylation_Deficiency_34.html#pathophysiology-impaired-mitochondrial-protein-synthesis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_34:pathophysiology:Impaired%20Oxidative%20Phosphorylation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Oxidative Phosphorylation","description":"With three of the four electron-transport complexes deficient, oxidative ATP synthesis falls. This is the bioenergetic endpoint that disease-specific mitochondrial lesions converge on, and the node conforms to the shared mitochondrial_dysfunction module at that point, as the sibling entry COXPD48 does.\nThe module's central effector state pairs falling oxidative phosphorylation with rising reactive oxygen species. Only the first half is claimed here: no ROS measurement has been reported in an MRPS7 patient, and asserting the second half would import a claim from the module rather than from this disease.\nThe consequence of the failing chain that these patients actually show is downstream - the cytosolic redox shift and the lactic acidemia, which are their own node.","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Oxidative_Phosphorylation_Deficiency_34.html#pathophysiology-impaired-oxidative-phosphorylation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Combined_Oxidative_Phosphorylation_Deficiency_34.yaml:Lentiviral wild-type MRPS7 complementation of patient 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No direct measurement of MRPS7 protein abundance in patient cells is reported in the sources cited here, so this node is an inference from the assembly and rRNA phenotypes below rather than a measured quantity.","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Oxidative_Phosphorylation_Deficiency_34.html#pathophysiology-destabilization-of-the-us7m-protein-of-the-mitoribosomal-small-subunit","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_34:pathophysiology:Impaired%20Mitochondrial%20Protein%20Synthesis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Mitochondrial Protein Synthesis","description":"Pulse labelling of mitochondrial translation products in patient fibroblasts showed impaired mitochondrial protein synthesis. 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The published account available here states the result without the per-line detail - which measurements were made, and how completely each line recovered - so this record does not characterise the magnitude of the rescue.","notes":null,"context_id":"disorder:Mitochondrial_Complex_I_Deficiency_Nuclear_Type_32","context_kind":"Disorder","disease_name":"Mitochondrial Complex I Deficiency, Nuclear Type 32","disease_synonyms":["MC1DN32","mitochondrial complex 1 deficiency, nuclear type 32","NDUFB8-related mitochondrial complex I deficiency","NDUFB8-related primary mitochondrial disease","NDUFB8 deficiency"],"disease_term":{"id":"MONDO:0032635","label":"mitochondrial complex I deficiency, nuclear type 32","display_label":"Mitochondrial complex I deficiency, nuclear type 32","url":"http://purl.obolibrary.org/obo/MONDO_0032635"},"experimental_model_type":"PRIMARY_CELL_CULTURE","experimental_model_type_label":"Primary-cell culture","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":null,"source_category":"Primary / biopsy-derived","culture_system":null,"publication":null,"publication_url":null,"mechanisms":[{"target":"Isolated Complex I Enzyme Deficiency","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_32.html#pathophysiology-isolated-complex-i-enzyme-deficiency","relationship":"RESCUES","relationship_label":"Rescues","fidelity":"HIGH","fidelity_label":"High","description":"Supplying wild-type NDUFB8 to the patients' own cells restores mitochondrial function, which is the demonstration that the NDUFB8 variants rather than something else in those genomes cause the enzyme defect.","limitations":"A cultured patient cell line, so it says nothing about brain, heart or muscle in vivo. The rescue is reported as a restoration of \"mitochondrial function\" without the assay being named in the abstract available here, so the readout below records the claim at the level the source makes it. Complementation of a recessive loss-of-function allele by lentiviral overexpression is also non-physiological in level and timing.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0006120","label":"mitochondrial electron transport, NADH to ubiquinone","display_label":"mitochondrial electron transport, NADH to ubiquinone","url":"http://purl.obolibrary.org/obo/GO_0006120"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Restoration of mitochondrial function after wild-type NDUFB8 expression","description":null,"target":"Isolated Complex I Enzyme Deficiency","direction":"RESTORED","interpretation":"Mitochondrial function in patient cells returns toward normal when wild-type NDUFB8 is supplied. 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The deficiency is isolated, which is what places the entity among the complex I deficiencies rather than among the combined oxidative phosphorylation defects. Residual activity figures for the individual patients are not given in the sources available here.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_32.html#pathophysiology-isolated-complex-i-enzyme-deficiency","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_32:phenotype:Decreased%20Activity%20of%20Mitochondrial%20Complex%20I","kind":"phenotype","kind_label":"Phenotype","label":"Decreased Activity of Mitochondrial Complex I","description":"The defining biochemical finding: an isolated reduction of complex I enzymatic activity, demonstrated in both skeletal muscle and cultured fibroblasts, with the other respiratory chain complexes unaffected.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_32.html#phenotype-decreased-activity-of-mitochondrial-complex-i","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_32:pathophysiology:Failure%20of%20Complex%20I%20Holoenzyme%20Assembly","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Failure of Complex I Holoenzyme Assembly","description":"Without NDUFB8 the enzyme does not assemble. 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The general rule established by that survey - that losing one subunit destabilises the other subunits of its own structural module - is the mechanism by which a single missing brace propagates into a whole-enzyme failure.\nThe knockout evidence is a complete null; the patient alleles are not, which is why this node is written as a failure of assembly rather than an absence of the enzyme, and why patients retain measurable residual activity.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_32.html#pathophysiology-failure-of-complex-i-holoenzyme-assembly","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_32:pathophysiology:Impaired%20NADH-Linked%20Oxidative%20Phosphorylation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired NADH-Linked Oxidative Phosphorylation","description":"Complex I is the entry point for NADH-derived electrons into the respiratory chain and pumps four protons per NADH oxidised, so a complex I defect cuts both the electron flux into the chain and the proton-motive force that drives ATP synthesis. Cells retain succinate-driven, complex II-dependent respiration, which is why the defect is survivable at all and why severity tracks residual complex I activity and tissue energy demand rather than being uniformly lethal.\nThis node is a mechanistic inference from the measured enzyme deficiency above rather than a separately measured quantity in these patients: no respirometry or ATP-synthesis measurement from an NDUFB8 patient is reported in the sources cited here, beyond the statement that complementation restored mitochondrial 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deficiency.","Establishes that this cell system is informative for the enzyme-deficiency node it is linked to."],"evidence_status":"Evidence recorded","metadata_completeness":30,"metadata_present":["Model category","Modeled mechanism","Evidence"],"metadata_missing":["NAMO class","Organism","Anatomy","Cell type","Cell source","Culture system","Publication"],"dataset_context":"None recorded in same 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Multiple Respiratory Chain Deficiencies.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Fibroblast cell lines from affected individuals were transfected with a lentiviral vector carrying a copy of the wild-type TRMT10C gene encoding MRPP1.","explanation":"Describes the model system used to establish causality."},{"reference":"PMID:27132592","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/27132592","reference_title":"Recessive Mutations in TRMT10C Cause Defects in Mitochondrial RNA Processing and Multiple Respiratory Chain Deficiencies.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The complemented cell lines displayed increased expression of MRPP1 protein level (Figure 4A), leading to a restoration of mitochondrial translation (Figures 4A and 4B) and normal levels of fully assembled respiratory chain complexes (Figure 4C).","explanation":"Reports restoration of translation and complex assembly after transduction."},{"reference":"PMID:27132592","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/27132592","reference_title":"Recessive Mutations in TRMT10C Cause Defects in Mitochondrial RNA Processing and Multiple Respiratory Chain Deficiencies.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Furthermore, the level of mt-RNA precursors, elevated in subject fibroblasts, normalized after lentiviral transduction with wild-type TRMT10C.","explanation":"Reports normalisation of the processing defect itself."}],"evidence_text":["Fibroblast cell lines from affected individuals were transfected with a lentiviral vector carrying a copy of the wild-type TRMT10C gene encoding MRPP1.","The complemented cell lines displayed increased expression of MRPP1 protein level (Figure 4A), leading to a restoration of mitochondrial translation (Figures 4A and 4B) and normal levels of fully assembled respiratory chain complexes (Figure 4C).","Furthermore, the level of mt-RNA precursors, elevated in subject fibroblasts, normalized after lentiviral transduction with wild-type TRMT10C.","Describes the model system used to establish causality.","Reports restoration of translation and complex assembly after transduction.","Reports normalisation of the processing defect itself."],"evidence_status":"Evidence recorded","metadata_completeness":30,"metadata_present":["Model category","Modeled mechanism","Evidence"],"metadata_missing":["NAMO class","Organism","Anatomy","Cell type","Cell source","Culture system","Publication"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Combined_Oxidative_Phosphorylation_Defect_Type_30.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Combined_Oxidative_Phosphorylation_Defect_Type_30.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Oxidative_Phosphorylation_Defect_Type_30.html#experimental-model-lentiviral-wild-type-trmt10c-complementation-of-patient-fibroblasts","source_anchor":"experimental-model-lentiviral-wild-type-trmt10c-complementation-of-patient-fibroblasts"},{"id":"model:kb/disorders/Rheumatic_Heart_Disease.yaml:Lewis rat autoimmune valvulitis model","name":"Lewis rat autoimmune valvulitis model","description":"The principal animal model, produced by immunising Lewis rats with streptococcal M protein or cardiac myosin. 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It reproduces the valvulitis and the cross-reactive immune response, which is what established molecular mimicry as more than an observation about sequence similarity. It is explicitly the subject of a published discussion of what a robust model of this disease would have to demonstrate, which is a fair signal that the existing models are not considered settled.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Rheumatic_Heart_Disease.html#experimental-model-lewis-rat-autoimmune-valvulitis-model","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ARheumatic_Heart_Disease:pathophysiology:Molecular%20mimicry%20and%20cross-reactive%20immune%20priming","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Molecular mimicry and cross-reactive immune priming","description":"The group A carbohydrate epitope N-acetylglucosamine and the alpha-helical coiled-coil M protein structurally resemble human cardiac myosin and connective tissue proteins closely enough that antibodies and T cells raised against the organism bind host tissue. Which host protein is struck first is genuinely disputed and is curated as a controversy rather than as settled fact. The long-standing answer is cardiac myosin, but myosin is intracellular and therefore hard to reach, which motivates an alternative in which extracellular proteins are hit first.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Rheumatic_Heart_Disease.html#pathophysiology-molecular-mimicry-and-cross-reactive-immune-priming","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ARheumatic_Heart_Disease:pathophysiology:Cross-reactive%20antibody%20binding%20and%20valve%20endothelial%20activation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Cross-reactive antibody binding and valve endothelial activation","description":"Cross-reactive antibody binds valve endothelium and upregulates VCAM-1, converting the valve surface from a quiescent lining into an adhesive one. This is the step that recruits the cellular infiltrate; antibody alone does not destroy the valve.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Rheumatic_Heart_Disease.html#pathophysiology-cross-reactive-antibody-binding-and-valve-endothelial-activation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ARheumatic_Heart_Disease:phenotype:Fever","kind":"phenotype","kind_label":"Phenotype","label":"Fever","description":"A minor Jones criterion during the acute episode.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Rheumatic_Heart_Disease.html#phenotype-fever","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ARheumatic_Heart_Disease:pathophysiology:Group%20A%20streptococcal%20infection%20in%20a%20susceptible%20host","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Group A streptococcal infection in a susceptible host","description":"Pharyngeal infection with Streptococcus pyogenes is the initiating event. Skin infection is an increasingly recognised alternative portal in high-burden tropical settings. Susceptibility is conferred largely by HLA class II genotype, which determines which streptococcal and self peptides are presented to CD4-positive T cells, so the same exposure produces disease in some hosts and not others.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Rheumatic_Heart_Disease.html#pathophysiology-group-a-streptococcal-infection-in-a-susceptible-host","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ARheumatic_Heart_Disease:phenotype:Migratory%20polyarthritis","kind":"phenotype","kind_label":"Phenotype","label":"Migratory polyarthritis","description":"An acute rheumatic fever manifestation rather than a feature of the chronic valvular disease. Classically large-joint, fleeting, asymmetric, and strikingly aspirin-responsive.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Rheumatic_Heart_Disease.html#phenotype-migratory-polyarthritis","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ARheumatic_Heart_Disease:phenotype:Subcutaneous%20nodules","kind":"phenotype","kind_label":"Phenotype","label":"Subcutaneous nodules","description":"Firm painless nodules over extensor surfaces. Uncommon, but they almost always accompany carditis, which makes them a useful clinical marker of cardiac involvement.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Rheumatic_Heart_Disease.html#phenotype-subcutaneous-nodules","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ARheumatic_Heart_Disease:phenotype:Sydenham%20chorea","kind":"phenotype","kind_label":"Phenotype","label":"Sydenham chorea","description":"A delayed neurological manifestation appearing one to eight months after the streptococcal infection, long after the other features have resolved, which is why it is accepted on its own as presumptive evidence of acute rheumatic fever. Most affected individuals have concurrent cardiac involvement.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Rheumatic_Heart_Disease.html#phenotype-sydenham-chorea","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Rheumatic_Heart_Disease.yaml:Lewis rat autoimmune valvulitis model","source_id":"model:kb/disorders/Rheumatic_Heart_Disease.yaml:Lewis rat autoimmune valvulitis model","target_id":"node:disorder%3ARheumatic_Heart_Disease:pathophysiology:Molecular%20mimicry%20and%20cross-reactive%20immune%20priming","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Not Specified","directed":false,"relationship":"NOT_SPECIFIED","fidelity":"NOT_SPECIFIED","causal_link_type":null,"causal_link_type_label":null,"description":"Immunisation with M protein or cardiac myosin reproduces the cross-reactive response.\n","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ARheumatic_Heart_Disease:0:0","source_id":"node:disorder%3ARheumatic_Heart_Disease:pathophysiology:Group%20A%20streptococcal%20infection%20in%20a%20susceptible%20host","target_id":"node:disorder%3ARheumatic_Heart_Disease:pathophysiology:Molecular%20mimicry%20and%20cross-reactive%20immune%20priming","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Antigens of the organism prime an immune response that does not distinguish them from host cardiac and connective tissue proteins.\n","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ARheumatic_Heart_Disease:1:0","source_id":"node:disorder%3ARheumatic_Heart_Disease:pathophysiology:Molecular%20mimicry%20and%20cross-reactive%20immune%20priming","target_id":"node:disorder%3ARheumatic_Heart_Disease:pathophysiology:Cross-reactive%20antibody%20binding%20and%20valve%20endothelial%20activation","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Cross-reactive antibody binds the valve surface, whichever host protein it recognises first.\n","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ARheumatic_Heart_Disease:1:4","source_id":"node:disorder%3ARheumatic_Heart_Disease:pathophysiology:Molecular%20mimicry%20and%20cross-reactive%20immune%20priming","target_id":"node:disorder%3ARheumatic_Heart_Disease:phenotype:Fever","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[4]","label":"Indirectly causes (known intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_KNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Known Intermediates","description":"The systemic inflammatory response accompanying the cross-reactive attack produces the fever that is a minor Jones criterion during the acute episode.\n","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ARheumatic_Heart_Disease:1:1","source_id":"node:disorder%3ARheumatic_Heart_Disease:pathophysiology:Molecular%20mimicry%20and%20cross-reactive%20immune%20priming","target_id":"node:disorder%3ARheumatic_Heart_Disease:phenotype:Migratory%20polyarthritis","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[1]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"The same cross-reactive response deposits in synovium, producing the fleeting large-joint arthritis of the acute episode. 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It reproduces the valvulitis and the cross-reactive immune response, which is what established molecular mimicry as more than an observation about sequence similarity. 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The Aschoff body is a pathological structure formed de novo and so is conceptually an Xogenesis lesion, but it is deliberately not curated as conforming to the granuloma_formation module. That module models containment of an indigestible persistent stimulus by macrophage fusion, and here there is no organism in the tissue to contain.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Rheumatic_Heart_Disease.html#pathophysiology-acute-valvulitis-with-aschoff-body-formation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ARheumatic_Heart_Disease:pathophysiology:CD4-positive%20T%20cell%20infiltration%20of%20the%20valve","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"CD4-positive T cell infiltration of the valve","description":"CD4-positive T lymphocytes showing degenerate, cross-reactive antigen recognition infiltrate valve tissue and myocardium and are considered the prime effectors of valve destruction. 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The EBV-transformed lymphoblast line from the founding family (PMID:25385316), in which the reduced charged mt-tRNA-Asn was first shown, is not recorded as a separate model: that paper reports it as a single measurement in patient material rather than as a manipulable system, and its result is already curated as evidence on the tRNA node.","context_id":"disorder:Combined_Oxidative_Phosphorylation_Defect_Type_24","context_kind":"Disorder","disease_name":"Combined Oxidative Phosphorylation Defect Type 24","disease_synonyms":["COXPD24","combined oxidative phosphorylation deficiency 24","combined oxidative phosphorylation defect type 24","NARS2-related mitochondrial disease","NARS2 deficiency","DFNB94"],"disease_term":{"id":"MONDO:0014547","label":"combined oxidative phosphorylation defect type 24","display_label":"combined oxidative phosphorylation defect type 24","url":"http://purl.obolibrary.org/obo/MONDO_0014547"},"experimental_model_type":"PRIMARY_CELL_CULTURE","experimental_model_type_label":"Primary-cell culture","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},"organism_label":"Homo sapiens","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[{"id":"GO:0005739","label":"mitochondrion","display_label":"mitochondrion","url":"http://purl.obolibrary.org/obo/GO_0005739"}],"linked_anatomy_labels":["mitochondrion"],"anatomy":[{"id":"GO:0005739","label":"mitochondrion","display_label":"mitochondrion","url":"http://purl.obolibrary.org/obo/GO_0005739"}],"anatomy_labels":["mitochondrion"],"tissue_label":null,"model_cell_types":[{"id":"CL:0000057","label":"fibroblast","display_label":"dermal fibroblast","url":"http://purl.obolibrary.org/obo/CL_0000057"}],"model_cell_type_labels":["fibroblast"],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[{"id":"CL:0000057","label":"fibroblast","display_label":"dermal fibroblast","url":"http://purl.obolibrary.org/obo/CL_0000057"}],"cell_type_labels":["fibroblast"],"conditions":[],"cell_source":"Dermal fibroblasts from proband II.1 of family LS06, compound heterozygous for c.969T>A p.Tyr323* and c.1142A>G p.Asn381Ser, stably transduced by lentivirus with cDNA encoding either wild-type NARS2 or the DFNB94 allele p.Val213Phe.","source_category":"Primary / biopsy-derived","culture_system":"Adherent monolayer. 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complex I is disproportionately affected, and in neurons the deficient complex is actively cleared by mitophagy.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0}]}}],"mechanism_names":["Complex I-predominant deficiency and neuronal mitophagy"],"relationships":["Recapitulates"],"fidelities":["Moderate"],"biological_scales":["Cellular"],"system_context_sources":["Model-level cell type","Linked mechanism cell type","Linked mechanism biological scale"],"modeled_system_labels":["neuron","Cellular"],"biological_process_terms":[{"id":"GO:0000422","label":"autophagy of mitochondrion","display_label":"autophagy of mitochondrion","url":"http://purl.obolibrary.org/obo/GO_0000422"}],"biological_processes":["autophagy of mitochondrion"],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":["Respiratory chain complex I deficiency","Perinuclear PINK1/Parkin-positive autophagosomal sequestration of complex I"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:38139018","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38139018","reference_title":"MELAS-Derived Neurons Functionally Improve by Mitochondrial Transfer from Highly Purified Mesenchymal Stem Cells (REC).","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Here, utilizing induced pluripotent stem cells (iPSC), we differentiated neurons with impaired mitochondrial function from patients with MELAS.","explanation":"Independent derivation of MELAS iPSC neurons with an impaired-mitochondrial-function phenotype, used as a therapeutic testbed."},{"reference":"PMID:24003133","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/24003133","reference_title":"Tissue- and cell-type-specific manifestations of heteroplasmic mtDNA 3243A>G mutation in human induced pluripotent stem cell-derived disease model.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Our data show that cellular context actively modifies RC deficiency manifestation in MELAS and that autophagy is a significant component of neuronal MELAS pathogenesis.","explanation":"The authors' own statement that the model is informative for neuronal MELAS pathogenesis."},{"reference":"PMID:24003133","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/24003133","reference_title":"Tissue- and cell-type-specific manifestations of heteroplasmic mtDNA 3243A>G mutation in human induced pluripotent stem cell-derived disease model.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Induced pluripotent stem cell-derived neurons and various tissues derived from teratomas manifested cell-type specific respiratory chain (RC) deficiency patterns. Similar to MELAS patient tissues, complex I defect predominated.","explanation":"The measurement establishing complex I predominance in the model and its correspondence to patient tissue."},{"reference":"PMID:24003133","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/24003133","reference_title":"Tissue- and cell-type-specific manifestations of heteroplasmic mtDNA 3243A>G mutation in human induced pluripotent stem cell-derived disease model.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Upon neuronal differentiation, complex I specifically was sequestered in perinuclear PTEN-induced putative kinase 1 (PINK1) and Parkin-positive autophagosomes, suggesting active degradation through mitophagy.","explanation":"The imaging readout supporting selective mitophagy of complex I in neurons."}],"evidence_text":["Here, utilizing induced pluripotent stem cells (iPSC), we differentiated neurons with impaired mitochondrial function from patients with MELAS.","Our data show that cellular context actively modifies RC deficiency manifestation in MELAS and that autophagy is a significant component of neuronal MELAS pathogenesis.","Induced pluripotent stem cell-derived neurons and various tissues derived from teratomas manifested cell-type specific respiratory chain (RC) deficiency patterns. Similar to MELAS patient tissues, complex I defect predominated.","Upon neuronal differentiation, complex I specifically was sequestered in perinuclear PTEN-induced putative kinase 1 (PINK1) and Parkin-positive autophagosomes, suggesting active degradation through mitophagy.","Independent derivation of MELAS iPSC neurons with an impaired-mitochondrial-function phenotype, used as a therapeutic testbed.","The authors' own statement that the model is informative for neuronal MELAS pathogenesis.","The measurement establishing complex I predominance in the model and its correspondence to patient tissue.","The imaging readout supporting selective mitophagy of complex I in neurons."],"evidence_status":"Evidence recorded","metadata_completeness":60,"metadata_present":["Model category","Organism","Cell type","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Anatomy","Cell source","Culture system"],"dataset_context":"Available in same entry","context_dataset_ids":["dataset:geo:gse113300","dataset:geo:gse127478","dataset:geo:gse129091","dataset:geo:gse1462","dataset:geo:gse14882","dataset:geo:gse154825","dataset:geo:gse165953","dataset:geo:gse202747","dataset:geo:gse27545","dataset:geo:gse324301","dataset:geo:gse56158","dataset:geo:gse61390","dataset:geo:gse85549","dataset:geo:gse89066","dataset:massive:msv000088237","dataset:pride:pxd058785"],"candidate_dataset_ids":[],"source_path":"kb/disorders/MELAS_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MELAS_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/MELAS_Syndrome.html#experimental-model-m-3243a-g-patient-ipsc-derived-neurons","source_anchor":"experimental-model-m-3243a-g-patient-ipsc-derived-neurons"},{"id":"model:kb/disorders/Immunodeficiency_25.yaml:MA5.8 murine CD247-deficient T-cell line","name":"MA5.8 murine CD247-deficient T-cell line","description":"The classic CD247-deficient mouse T-cell line, long used as the reconstitution background for zeta-chain work. 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A reconstitution result obtained in MA5.8 cannot be assumed to transfer to human CD247 deficiency, and the direction of the error is optimistic — it makes a damaging allele look tolerated.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[{"id":"CL:0000791","label":"mature alpha-beta T cell","display_label":"mature alpha-beta T cell","url":"http://purl.obolibrary.org/obo/CL_0000791"}],"biological_processes":[],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Surface TCR/CD3 expression after Q70X reconstitution","description":null,"target":"Impaired TCR/CD3 Complex Assembly and Surface Expression","direction":"RESTORED","interpretation":"Restored in the murine line and not in human cells; the discrepancy is the finding, not the restoration.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:40711587","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40711587","reference_title":"Discordant Restoration of TCR Expression and Function by CD247 Somatic Reversions.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"MA5.8 mouse T cells do not accurately model human CD247 deficiencies, as Q70X restores TCR expression in MA5.8 but not in human cells.","explanation":"Reports the divergent reconstitution result in the two species."}],"notes":null}],"evidence":[{"reference":"PMID:40711587","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40711587","reference_title":"Discordant Restoration of TCR Expression and Function by CD247 Somatic Reversions.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"MA5.8 mouse T cells do not accurately model human CD247 deficiencies, as Q70X restores TCR expression in MA5.8 but not in human cells.","explanation":"States directly that the murine line does not model the human disorder."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Immunodeficiency_25","model_node_id":"model:kb/disorders/Immunodeficiency_25.yaml:MA5.8 murine CD247-deficient T-cell line","focus_node_id":"node:disorder%3AImmunodeficiency_25:pathophysiology:Impaired%20TCR%2FCD3%20Complex%20Assembly%20and%20Surface%20Expression","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Immunodeficiency_25.html#pathograph","nodes":[{"id":"model:kb/disorders/Immunodeficiency_25.yaml:MA5.8 murine CD247-deficient T-cell line","kind":"experimental_model","kind_label":"NAM model","label":"MA5.8 murine CD247-deficient T-cell line","description":"The classic CD247-deficient mouse T-cell line, long used as the reconstitution background for zeta-chain work. 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This was in fact the first biochemical description of the disorder, made before the gene was identified, as a failure of the zeta chain to associate with the rest of the complex.","url":"https://dismech.monarchinitiative.org/pages/disorders/Immunodeficiency_25.html#pathophysiology-impaired-tcr-cd3-complex-assembly-and-surface-expression","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AImmunodeficiency_25:pathophysiology:Biallelic%20CD247%20Loss-of-Function%20Variants","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Biallelic CD247 Loss-of-Function Variants","description":"Reported germline alleles include an initiation-codon change (p.M1T) and a nonsense change truncating the protein before all three ITAMs (p.Q70X). The two act differently: p.M1T abolishes translation initiation, while p.Q70X leaves a truncated chain that can still be detected intracellularly with a transmembrane-directed antibody but not with an ITAM-3-directed one. That distinction matters, because a retained truncated chain can compete with wild-type CD247 whereas a true null cannot.\nA third reported allele is a homozygous single-C insertion after nucleotide 411 in exon 7. It behaves as a true null at the protein level: no CD3zeta is detectable in the patient's T cells, and when the mutant cDNA is transduced into a CD247-deficient background the nascent protein is not detected at all on metabolic labelling, indicating it is made and then rapidly degraded. That completes the allelic picture — one allele class is degraded away, another is retained as a truncated competitor, and the two are not interchangeable when predicting a novel variant's behaviour.","url":"https://dismech.monarchinitiative.org/pages/disorders/Immunodeficiency_25.html#pathophysiology-biallelic-cd247-loss-of-function-variants","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AImmunodeficiency_25:pathophysiology:Loss%20of%20ITAM-Dependent%20Proximal%20TCR%20Signaling","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Loss of ITAM-Dependent Proximal TCR Signaling","description":"CD247 carries three of the ten ITAMs in the receptor complex. Their tyrosines are the docking sites that, once phosphorylated by LCK, recruit ZAP70 and start the proximal signalling cascade. In CD247 deficiency this step fails, and the failure is not repaired by restoring surface receptor: revertant variants that put the receptor back on the membrane still fail to support TCR-induced ZAP70 phosphorylation. The activation defect is therefore partly independent of receptor density.","url":"https://dismech.monarchinitiative.org/pages/disorders/Immunodeficiency_25.html#pathophysiology-loss-of-itam-dependent-proximal-tcr-signaling","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Immunodeficiency_25.yaml:MA5.8 murine CD247-deficient T-cell line","source_id":"model:kb/disorders/Immunodeficiency_25.yaml:MA5.8 murine CD247-deficient T-cell line","target_id":"node:disorder%3AImmunodeficiency_25:pathophysiology:Impaired%20TCR%2FCD3%20Complex%20Assembly%20and%20Surface%20Expression","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Fails To 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and activate ZAP70.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1}]}}],"mechanism_names":["Impaired TCR/CD3 Complex Assembly and Surface Expression"],"relationships":["Fails To Recapitulate"],"fidelities":["Low"],"biological_scales":["Molecular"],"system_context_sources":["Linked mechanism cell type","Linked mechanism biological scale"],"modeled_system_labels":["mature alpha-beta T cell","Molecular"],"biological_process_terms":[],"biological_processes":[],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":["Surface TCR/CD3 expression after Q70X reconstitution"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:40711587","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40711587","reference_title":"Discordant Restoration of TCR Expression 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This model tests site- and age-dependent paracrine response; it does not prove absence of receptors in every unaffected human follicle.","notes":null,"context_id":"disorder:Androgenetic_Alopecia","context_kind":"Disorder","disease_name":"Androgenetic Alopecia","disease_synonyms":["AGA","Androgenic alopecia","Pattern hair loss","Common baldness","Male pattern hair loss","Male pattern baldness","MPHL","Female pattern hair loss","FPHL","Alopecia androgenetica","AGA1"],"disease_term":{"id":"MONDO:0005339","label":"androgenetic alopecia","display_label":"Androgenetic Alopecia","url":"http://purl.obolibrary.org/obo/MONDO_0005339"},"experimental_model_type":"CO_CULTURE","experimental_model_type_label":"Co-culture","namo_type":"namo:CoCulture","declared_namo_class_name":null,"namo_class_name":"CoCulture","namo_class_label":"Co Culture","namo_description":"Co-culture systems combining multiple cell types to mimic  microenvironments and cell-cell interactions.","namo_docs_url":"https://monarch-initiative.github.io/namo/elements/CoCulture/","namo_ontology_url":"https://w3id.org/monarch-initiative/namo/CoCulture","namo_mapping_basis":"Safe mapping from DisMech category","namo_class_in_schema":true,"namo_schema_status":"Defined in NAMO schema used for this build","modality":"Cellular system","organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[{"id":"UBERON:0000412","label":"dermal papilla","display_label":"dermal papilla","url":"http://purl.obolibrary.org/obo/UBERON_0000412"}],"linked_anatomy_labels":["dermal papilla"],"anatomy":[{"id":"UBERON:0000412","label":"dermal papilla","display_label":"dermal papilla","url":"http://purl.obolibrary.org/obo/UBERON_0000412"}],"anatomy_labels":["dermal papilla"],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[{"id":"CL:2000083","label":"hair follicle dermal papilla cell of scalp","display_label":"hair follicle dermal papilla cell of scalp","url":"http://purl.obolibrary.org/obo/CL_2000083"}],"linked_cell_type_labels":["hair follicle dermal papilla cell of scalp"],"cell_types":[{"id":"CL:2000083","label":"hair follicle dermal papilla cell of scalp","display_label":"hair follicle dermal papilla cell of scalp","url":"http://purl.obolibrary.org/obo/CL_2000083"}],"cell_type_labels":["hair follicle dermal papilla cell of scalp"],"conditions":[],"cell_source":"Dermal papilla and outer-root-sheath cells from adult frontal/occipital and juvenile frontal macaque scalp","source_category":"Mixed / co-culture","culture_system":null,"publication":null,"publication_url":null,"mechanisms":[{"target":"Dihydrotestosterone-Androgen Receptor Signaling","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Androgenetic_Alopecia.html#pathophysiology-dihydrotestosterone-androgen-receptor-signaling","relationship":"PERTURBS","relationship_label":"Perturbs","fidelity":"MODERATE","fidelity_label":"Moderate","description":"Testosterone and an AR blocker probe androgen-dependent epithelial inhibition mediated by dermal papilla cells.","limitations":"The applied androgen is testosterone; 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Androgens stimulate growth at other body sites, so signaling consequences depend on follicular context.","url":"https://dismech.monarchinitiative.org/pages/disorders/Androgenetic_Alopecia.html#pathophysiology-dihydrotestosterone-androgen-receptor-signaling","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAndrogenetic_Alopecia:pathophysiology:Increased%20DKK1%20Secretion","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Increased DKK1 Secretion","description":"DHT increased DKK1 expression and secretion in human dermal papilla cultures. DKK1 protein was also higher in bald than haired patient scalp. 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The measured signaling compartment is dermal papilla; this is separate from the reduced marker-defined progenitor populations observed in patient scalp.","url":"https://dismech.monarchinitiative.org/pages/disorders/Androgenetic_Alopecia.html#pathophysiology-reduced-canonical-wnt-signaling-in-dermal-papilla-cells","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAndrogenetic_Alopecia:pathophysiology:Regional%20Androgen%20Receptor%20Abundance","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Regional Androgen Receptor Abundance","description":"Frontal follicles contained more androgen receptor than occipital follicles in a small paired study, with lower frontal abundance in women than men. 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The source explicitly notes that the severely reduced NK cell number precluded precise quantification of this distribution.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Immunodeficiency_80_with_or_without_Congenital_Cardiomyopathy.html#phenotype-abnormal-cd56bright-cd56dim-nk-cell-subset-distribution","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AImmunodeficiency_80_with_or_without_Congenital_Cardiomyopathy:pathophysiology:Chronic%20Replication%20Stress%20and%20Genomic%20Instability","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Chronic Replication Stress and Genomic Instability","description":"Reduced MCM10 function impairs CMG helicase activity, causing chronic replication stress with accumulation of terminally arrested, single-strand-DNA-enriched replication fork structures. These abnormal forks require endonucleolytic processing by MUS81; in MCM10:MUS81 double-mutant cells, viability falls further and telomere shortening accelerates, indicating that MUS81-dependent fork processing is a downstream node that itself contributes to (rather than merely reads out) the genomic instability.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Immunodeficiency_80_with_or_without_Congenital_Cardiomyopathy.html#pathophysiology-chronic-replication-stress-and-genomic-instability","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AImmunodeficiency_80_with_or_without_Congenital_Cardiomyopathy:phenotype:Severely%20Decreased%20Mature%20NK%20Cells","kind":"phenotype","kind_label":"Phenotype","label":"Severely Decreased Mature NK Cells","description":"Profound 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differentiation of induced pluripotent stem cells into natural killer cells.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Although MCM10+/- HSCs were able to give rise to lymphoid progenitors, these did not generate mature NK cells.","explanation":"Directly reports the block at the mature NK cell stage in this model.\n"}],"evidence_text":["MCM10+/- iPSCs displayed defects in NK cell differentiation, exhibiting reduced yields of hematopoietic stem cells (HSCs).","Although MCM10+/- HSCs were able to give rise to lymphoid progenitors, these did not generate mature NK cells.","Establishes the MCM10+/- iPSC-NK differentiation system as informative for the NK terminal maturation mechanism node.","Directly reports the block at the mature NK cell stage in this model."],"evidence_status":"Evidence recorded","metadata_completeness":70,"metadata_present":["Model category","Organism","Cell type","Cell source","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Anatomy","Culture system"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Immunodeficiency_80_with_or_without_Congenital_Cardiomyopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Immunodeficiency_80_with_or_without_Congenital_Cardiomyopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Immunodeficiency_80_with_or_without_Congenital_Cardiomyopathy.html#experimental-model-mcm10-heterozygous-mcm10-ipsc-nk-differentiation","source_anchor":"experimental-model-mcm10-heterozygous-mcm10-ipsc-nk-differentiation"},{"id":"model:kb/disorders/Radioulnar_Synostosis_with_Amegakaryocytic_Thrombocytopenia.yaml:MECOM-haploinsufficient primary human hematopoietic stem cells","name":"MECOM-haploinsufficient primary human hematopoietic stem cells","description":"Primary human haematopoietic stem cells engineered to model MECOM haploinsufficiency, combined with single-cell genomics. This is the system that turned the disease from a gene assignment into a mechanism: it is where the EVI1-dependent maintenance network was defined, and it works in the species that has the disease, which the knock-in mouse does not.\n","notes":null,"context_id":"disorder:Radioulnar_Synostosis_with_Amegakaryocytic_Thrombocytopenia","context_kind":"Disorder","disease_name":"Radioulnar Synostosis with Amegakaryocytic Thrombocytopenia","disease_synonyms":["RUSAT","Radioulnar synostosis with amegakaryocytic thrombocytopenia","Amegakaryocytic thrombocytopenia with radio-ulnar synostosis","MECOM-associated syndrome","RUS-associated hematological disease","RUSHD"],"disease_term":{"id":"MONDO:0011555","label":"radio-ulnar synostosis-amegakaryocytic thrombocytopenia syndrome","display_label":"radio-ulnar synostosis-amegakaryocytic thrombocytopenia syndrome","url":"http://purl.obolibrary.org/obo/MONDO_0011555"},"experimental_model_type":"PRIMARY_CELL_CULTURE","experimental_model_type_label":"Primary-cell culture","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":null,"source_category":"Primary / biopsy-derived","culture_system":null,"publication":null,"publication_url":null,"mechanisms":[{"target":"Dysregulation of the EVI1 HSC Maintenance Network","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Radioulnar_Synostosis_with_Amegakaryocytic_Thrombocytopenia.html#pathophysiology-dysregulation-of-the-evi1-hsc-maintenance-network","relationship":"RECAPITULATES","relationship_label":"Recapitulates","fidelity":"HIGH","fidelity_label":"High","description":"Reproduces the human haploinsufficient state in human stem cells and reads out the transcriptional network directly.\n","limitations":"An engineered haploinsufficiency rather than the patient allelic spectrum, so it models dose reduction and cannot address whether the zinc-finger 8/9 missense alleles do anything a null does not - which is exactly the question the two competing hypotheses in this entry turn on. It is also a cell-autonomous system with no marrow niche and no limb.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0007179","label":"transforming growth factor beta receptor signaling pathway","display_label":"TGF-beta-mediated transcriptional response","url":"http://purl.obolibrary.org/obo/GO_0007179"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"HSC maintenance transcriptional network expression","description":null,"target":"Dysregulation of the EVI1 HSC Maintenance Network","direction":"ALTERED","interpretation":"Single-cell genomic definition of the gene network EVI1 maintains.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:36522544","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/36522544","reference_title":"A genetic disorder reveals a hematopoietic stem cell regulatory network co-opted in leukemia.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"By generating a faithful model of this disorder in primary human HSCs and coupling functional studies with integrative single-cell genomic analyses, we uncover a key transcriptional network involving hundreds of genes that is required for HSC maintenance.","explanation":"The network readout that this model exists to produce."}],"notes":null}],"evidence":[{"reference":"PMID:36522544","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/36522544","reference_title":"A genetic disorder reveals a hematopoietic stem cell regulatory network co-opted in leukemia.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Here, we have studied a rare genetic disorder due to MECOM haploinsufficiency, characterized by an early-onset absence of HSCs in vivo.","explanation":"Establishes that the system models this disorder specifically."},{"reference":"PMID:36522544","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/36522544","reference_title":"A genetic disorder reveals a hematopoietic stem cell regulatory network co-opted in leukemia.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"By generating a faithful model of this disorder in primary human HSCs and coupling functional studies with integrative single-cell genomic analyses, we uncover a key transcriptional network involving hundreds of genes that is required for HSC maintenance.","explanation":"The network readout that this model exists to produce."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Radioulnar_Synostosis_with_Amegakaryocytic_Thrombocytopenia","model_node_id":"model:kb/disorders/Radioulnar_Synostosis_with_Amegakaryocytic_Thrombocytopenia.yaml:MECOM-haploinsufficient primary human hematopoietic stem cells","focus_node_id":"node:disorder%3ARadioulnar_Synostosis_with_Amegakaryocytic_Thrombocytopenia:pathophysiology:Dysregulation%20of%20the%20EVI1%20HSC%20Maintenance%20Network","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Radioulnar_Synostosis_with_Amegakaryocytic_Thrombocytopenia.html#pathograph","nodes":[{"id":"model:kb/disorders/Radioulnar_Synostosis_with_Amegakaryocytic_Thrombocytopenia.yaml:MECOM-haploinsufficient primary human hematopoietic stem cells","kind":"experimental_model","kind_label":"NAM model","label":"MECOM-haploinsufficient primary human hematopoietic stem cells","description":"Primary human haematopoietic stem cells engineered to model MECOM haploinsufficiency, combined with single-cell genomics. This is the system that turned the disease from a gene assignment into a mechanism: it is where the EVI1-dependent maintenance network was defined, and it works in the species that has the disease, which the knock-in mouse does not.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Radioulnar_Synostosis_with_Amegakaryocytic_Thrombocytopenia.html#experimental-model-mecom-haploinsufficient-primary-human-hematopoietic-stem-cells","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ARadioulnar_Synostosis_with_Amegakaryocytic_Thrombocytopenia:pathophysiology:Dysregulation%20of%20the%20EVI1%20HSC%20Maintenance%20Network","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Dysregulation of the EVI1 HSC Maintenance Network","description":"The central node of the MECOM arm, and the point at which one molecular lesion becomes several tissue phenotypes. EVI1 does not maintain haematopoietic stem cells through a single target: it binds regulatory enhancers controlling a network of hundreds of genes, and modelling MECOM haploinsufficiency in primary human haematopoietic stem cells shows that network is required for stem-cell maintenance. Among its targets are GATA2, whose promoter EVI1 binds through the N-terminal zinc fingers, and MPL, the thrombopoietin receptor. EVI1 also prevents the CTCF-dependent genome reorganisation that normally accompanies differentiation, so the consequence of losing it is not simply reduced output of one factor.\nRead the magnitude carefully, because the phenotype is severe and the transcriptional change is not. The primary-human-HSC study describes a \"high degree of similarity\" in the single-cell transcriptome after MECOM perturbation and, on random permutation analysis, detected no differentially expressed genes at all. This node therefore asserts coordinated dysregulation of a defined network, not a wholesale collapse of transcription. That a small, coordinated shift produces an absence of stem cells is the interesting part, not an argument for a larger shift.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Radioulnar_Synostosis_with_Amegakaryocytic_Thrombocytopenia.html#pathophysiology-dysregulation-of-the-evi1-hsc-maintenance-network","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ARadioulnar_Synostosis_with_Amegakaryocytic_Thrombocytopenia:pathophysiology:Hematopoietic%20Stem%20Cell%20Maintenance%20Failure","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Hematopoietic Stem Cell Maintenance Failure","description":"Haematopoietic stem cells are not maintained. The human phenotype modelled in primary HSCs is described as an early-onset absence of stem cells in vivo, which is what distinguishes this disease from the inherited marrow failure syndromes that declare themselves in later childhood or adolescence. The severity tracks gene dosage, and the consequence is multilineage rather than lineage-restricted - which is the main reason the \"amegakaryocytic thrombocytopenia\" half of the disease name understates what is happening.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Radioulnar_Synostosis_with_Amegakaryocytic_Thrombocytopenia.html#pathophysiology-hematopoietic-stem-cell-maintenance-failure","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ARadioulnar_Synostosis_with_Amegakaryocytic_Thrombocytopenia:pathophysiology:Loss%20of%20EVI1%20Sequence-Specific%20DNA%20Binding","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Loss of EVI1 Sequence-Specific DNA Binding","description":"The zinc-finger 8/9 variants reduce EVI1 occupancy at its recognition sites. Protein modelling of the two mutational hotspots, zinc finger 6 and zinc fingers 8/9, predicts both are DNA-binding regions, so the variants are read as disabling contact with DNA rather than destabilising the protein as a whole. The functional consequence is measured on both sides of EVI1's dual role: it is a repressor at some targets and a permissive factor at others, and the variants shift both.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Radioulnar_Synostosis_with_Amegakaryocytic_Thrombocytopenia.html#pathophysiology-loss-of-evi1-sequence-specific-dna-binding","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ARadioulnar_Synostosis_with_Amegakaryocytic_Thrombocytopenia:pathophysiology:Loss%20of%20EVI1%20Transcriptional%20Control%20of%20MPL","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Loss of EVI1 Transcriptional Control of MPL","description":"EVI1 transcriptionally regulates MPL, the thrombopoietin receptor. Biallelic MPL loss is the cause of congenital amegakaryocytic thrombocytopenia, so this branch is the proposed mechanistic reason RUSAT and CAMT are hard to tell apart in a newborn with an amegakaryocytic marrow: they converge on the same receptor.\nThe node is deliberately named for a loss of control rather than for a direction, because the direction is not established and the obvious guess is probably backwards. What the assay shows is that the variant \"impairs the repressive activity of the transcription factor\" - and impaired repression would, on its face, raise MPL rather than lower it. No measurement of MPL message or thrombopoietin-receptor signalling in RUSAT patient megakaryocytes is cited here. `DYSREGULATED` is the honest tag until someone measures it; naming this node for a direction would export an assertion no source supports into the graph.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Radioulnar_Synostosis_with_Amegakaryocytic_Thrombocytopenia.html#pathophysiology-loss-of-evi1-transcriptional-control-of-mpl","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Radioulnar_Synostosis_with_Amegakaryocytic_Thrombocytopenia.yaml:MECOM-haploinsufficient primary human hematopoietic stem cells","source_id":"model:kb/disorders/Radioulnar_Synostosis_with_Amegakaryocytic_Thrombocytopenia.yaml:MECOM-haploinsufficient primary human hematopoietic stem cells","target_id":"node:disorder%3ARadioulnar_Synostosis_with_Amegakaryocytic_Thrombocytopenia:pathophysiology:Dysregulation%20of%20the%20EVI1%20HSC%20Maintenance%20Network","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"HIGH","causal_link_type":null,"causal_link_type_label":null,"description":"Reproduces the human haploinsufficient state in human stem cells and reads out the transcriptional network directly.\n","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ARadioulnar_Synostosis_with_Amegakaryocytic_Thrombocytopenia:4:1","source_id":"node:disorder%3ARadioulnar_Synostosis_with_Amegakaryocytic_Thrombocytopenia:pathophysiology:Dysregulation%20of%20the%20EVI1%20HSC%20Maintenance%20Network","target_id":"node:disorder%3ARadioulnar_Synostosis_with_Amegakaryocytic_Thrombocytopenia:pathophysiology:Hematopoietic%20Stem%20Cell%20Maintenance%20Failure","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[4].downstream[1]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ARadioulnar_Synostosis_with_Amegakaryocytic_Thrombocytopenia:4:0","source_id":"node:disorder%3ARadioulnar_Synostosis_with_Amegakaryocytic_Thrombocytopenia:pathophysiology:Dysregulation%20of%20the%20EVI1%20HSC%20Maintenance%20Network","target_id":"node:disorder%3ARadioulnar_Synostosis_with_Amegakaryocytic_Thrombocytopenia:pathophysiology:Loss%20of%20EVI1%20Transcriptional%20Control%20of%20MPL","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[4].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ARadioulnar_Synostosis_with_Amegakaryocytic_Thrombocytopenia:2:4","source_id":"node:disorder%3ARadioulnar_Synostosis_with_Amegakaryocytic_Thrombocytopenia:pathophysiology:Loss%20of%20EVI1%20Sequence-Specific%20DNA%20Binding","target_id":"node:disorder%3ARadioulnar_Synostosis_with_Amegakaryocytic_Thrombocytopenia:pathophysiology:Dysregulation%20of%20the%20EVI1%20HSC%20Maintenance%20Network","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[4]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Opted into `mecom_pure_haploinsufficiency` because this is the step the dose model explains well and the knock-in mouse supports: less functional EVI1 at its target sites, less of the network it maintains. 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A separate 2026 report describes intron-2 retention associated with c.180+5G>C.","url":"https://dismech.monarchinitiative.org/pages/disorders/Basel-Vanagaite-Smirin-Yosef_Syndrome.html#pathophysiology-abnormal-med25-pre-mrna-splicing","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ABasel-Vanagaite-Smirin-Yosef_Syndrome:pathophysiology:Biallelic%20MED25%20dysfunction","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Biallelic MED25 dysfunction","description":"Homozygous and compound heterozygous MED25 variants are associated with a variable developmental syndrome. Both missense and truncating alleles have been described, and splice defects have been demonstrated for particular intronic variants. 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The finding is not universal in individual patients — the 2024 Mexican case had normal coagulation tests.","url":"https://dismech.monarchinitiative.org/pages/disorders/ALG2-congenital_disorder_of_glycosylation.html#pathophysiology-hepatic-and-coagulation-glycoprotein-dysfunction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AALG2-Congenital_Disorder_of_Glycosylation:phenotype:Iris%20coloboma","kind":"phenotype","kind_label":"Phenotype","label":"Iris coloboma","description":"Coloboma of the iris was present in the index patient and is listed among the recurrent ophthalmological features of the disorder.","url":"https://dismech.monarchinitiative.org/pages/disorders/ALG2-congenital_disorder_of_glycosylation.html#phenotype-iris-coloboma","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AALG2-Congenital_Disorder_of_Glycosylation:pathophysiology:Neurodevelopmental%20and%20Myelination%20Failure","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Neurodevelopmental and Myelination Failure","description":"The classic multisystem form is dominated by central nervous system disease: global developmental delay with regression, intractable seizures including infantile spasms, and hypomyelination on imaging. The medaka model of the index patient's allele shows reduced white matter in mid- and hindbrain, matching the human imaging finding.","url":"https://dismech.monarchinitiative.org/pages/disorders/ALG2-congenital_disorder_of_glycosylation.html#pathophysiology-neurodevelopmental-and-myelination-failure","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AALG2-Congenital_Disorder_of_Glycosylation:pathophysiology:Neuromuscular%20Junction%20Glycoprotein%20Dysfunction","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Neuromuscular Junction Glycoprotein Dysfunction","description":"Hypoglycosylation at the motor endplate produces a failure of neuromuscular signal transmission. This is the mechanism of the CMS14 presentation, in which single-fibre electromyography shows transmission failure and the weakness is fatigable and limb-girdle in distribution rather than the generalised encephalopathy of the classic form.","url":"https://dismech.monarchinitiative.org/pages/disorders/ALG2-congenital_disorder_of_glycosylation.html#pathophysiology-neuromuscular-junction-glycoprotein-dysfunction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AALG2-Congenital_Disorder_of_Glycosylation:phenotype:Nystagmus","kind":"phenotype","kind_label":"Phenotype","label":"Nystagmus","description":"Nystagmus is recorded among the index patient's findings and is named in the ophthalmological features of the disorder. It is grouped with coloboma and strabismus in the one ocular row of the published feature table, so no nystagmus-specific denominator exists and none is asserted here.","url":"https://dismech.monarchinitiative.org/pages/disorders/ALG2-congenital_disorder_of_glycosylation.html#phenotype-nystagmus","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AALG2-Congenital_Disorder_of_Glycosylation:pathophysiology:Stalled%20Dolichol-Linked%20Oligosaccharide%20Assembly","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Stalled Dolichol-Linked Oligosaccharide Assembly","description":"ALG2 makes the first branch of the lipid-linked oligosaccharide, adding both the alpha-1,3- and alpha-1,6-mannose to Man1GlcNAc2-PP-dolichol to give the branched Man3GlcNAc2-PP-dolichol. When it is deficient the pathway backs up at the immediately preceding species: patient fibroblasts accumulate Man1GlcNAc2-PP-dolichol and Man2GlcNAc2-PP-dolichol instead of proceeding to the mature Glc3Man9GlcNAc2 donor.","url":"https://dismech.monarchinitiative.org/pages/disorders/ALG2-congenital_disorder_of_glycosylation.html#pathophysiology-stalled-dolichol-linked-oligosaccharide-assembly","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/ALG2-Congenital_Disorder_of_Glycosylation.yaml:Medaka alg2 p.G336* knock-in","source_id":"model:kb/disorders/ALG2-Congenital_Disorder_of_Glycosylation.yaml:Medaka alg2 p.G336* knock-in","target_id":"node:disorder%3AALG2-Congenital_Disorder_of_Glycosylation:pathophysiology:Protein%20Hypoglycosylation","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"Reduced N-glycan levels were measured in the fish and, in the same study, in the patient's fibroblasts, so the molecular phenotype is matched across species.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3AALG2-Congenital_Disorder_of_Glycosylation:2:2","source_id":"node:disorder%3AALG2-Congenital_Disorder_of_Glycosylation:pathophysiology:Protein%20Hypoglycosylation","target_id":"node:disorder%3AALG2-Congenital_Disorder_of_Glycosylation:pathophysiology:Hepatic%20and%20Coagulation%20Glycoprotein%20Dysfunction","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[2]","label":"Indirectly causes (known intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_KNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Known Intermediates","description":"Coagulation factors and their inhibitors are N-glycoproteins, so their hypoglycosylation is the proximate cause of the coagulopathy.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3AALG2-Congenital_Disorder_of_Glycosylation:2:3","source_id":"node:disorder%3AALG2-Congenital_Disorder_of_Glycosylation:pathophysiology:Protein%20Hypoglycosylation","target_id":"node:disorder%3AALG2-Congenital_Disorder_of_Glycosylation:phenotype:Iris%20coloboma","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[3]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"Coloboma is a failure of optic fissure closure in the embryo, so it is placed on the developmental branch of hypoglycosylation rather than downstream of photoreceptor maintenance. Which glycoprotein's hypoglycosylation causes the fissure to stay open is not known, hence unknown intermediates.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3AALG2-Congenital_Disorder_of_Glycosylation:2:1","source_id":"node:disorder%3AALG2-Congenital_Disorder_of_Glycosylation:pathophysiology:Protein%20Hypoglycosylation","target_id":"node:disorder%3AALG2-Congenital_Disorder_of_Glycosylation:pathophysiology:Neurodevelopmental%20and%20Myelination%20Failure","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[1]","label":"Indirectly causes (known intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_KNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Known Intermediates","description":"Hypoglycosylation of neuronal glycoproteins underlies the encephalopathy, hypomyelination and seizures of the multisystem form.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3AALG2-Congenital_Disorder_of_Glycosylation:2:0","source_id":"node:disorder%3AALG2-Congenital_Disorder_of_Glycosylation:pathophysiology:Protein%20Hypoglycosylation","target_id":"node:disorder%3AALG2-Congenital_Disorder_of_Glycosylation:pathophysiology:Neuromuscular%20Junction%20Glycoprotein%20Dysfunction","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[0]","label":"Indirectly causes (known intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_KNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Known Intermediates","description":"Acetylcholine receptor subunits and other endplate proteins are N-glycosylated, and glycosylation defects at this step impair neuromuscular transmission.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AALG2-Congenital_Disorder_of_Glycosylation:2:4","source_id":"node:disorder%3AALG2-Congenital_Disorder_of_Glycosylation:pathophysiology:Protein%20Hypoglycosylation","target_id":"node:disorder%3AALG2-Congenital_Disorder_of_Glycosylation:phenotype:Nystagmus","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[4]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"Grouped with coloboma on the developmental branch for the same reason. The source that quantifies the eye findings counts coloboma, strabismus and nystagmus together as one ocular category, so no route separating them is available.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3AALG2-Congenital_Disorder_of_Glycosylation:1:0","source_id":"node:disorder%3AALG2-Congenital_Disorder_of_Glycosylation:pathophysiology:Stalled%20Dolichol-Linked%20Oligosaccharide%20Assembly","target_id":"node:disorder%3AALG2-Congenital_Disorder_of_Glycosylation:pathophysiology:Protein%20Hypoglycosylation","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"A truncated lipid-linked oligosaccharide is a poor donor for the oligosaccharyltransferase, so glycosylation sequons go unoccupied.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1}]}},{"target":"Photoreceptor Maintenance Failure","target_url":"https://dismech.monarchinitiative.org/pages/disorders/ALG2-congenital_disorder_of_glycosylation.html#pathophysiology-photoreceptor-maintenance-failure","relationship":"RECAPITULATES","relationship_label":"Recapitulates","fidelity":"LOW","fidelity_label":"Low","description":"Progressive rod loss with under-representation of phototransduction proteins. This is the model's most striking finding and its least transferable one.","limitations":"No human ALG2-CDG patient has been reported with retinitis pigmentosa. Teleost and mammalian retinas differ in rod regeneration capacity and in photoreceptor turnover, and the fish dies within days of hatching, so the timescale has no human counterpart. The node this links to exists only to hold the model finding.","biological_scale":"TISSUE","anatomy":[],"cell_types":[],"biological_processes":[],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Rod photoreceptor number","description":null,"target":"Photoreceptor Maintenance Failure","direction":"DECREASED","interpretation":"Progressive elimination of rods over the fish's short lifespan.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:34106226","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/34106226","reference_title":"A patient-based medaka alg2 mutant as a model for hypo-N-glycosylation.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"These deficiencies relate to a specific failure to maintain rod photoreceptors, resulting in retinitis pigmentosa characterized by the progressive loss of these photoreceptors.","explanation":"The rod-loss result."}],"notes":null}],"evidence":[{"reference":"PMID:34106226","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/34106226","reference_title":"A patient-based medaka alg2 mutant as a model for hypo-N-glycosylation.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"These deficiencies relate to a specific failure to maintain rod photoreceptors, resulting in retinitis pigmentosa characterized by the progressive loss of these photoreceptors.","explanation":"The rod-loss result."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"isolated","context_id":"disorder:ALG2-Congenital_Disorder_of_Glycosylation","model_node_id":"model:kb/disorders/ALG2-Congenital_Disorder_of_Glycosylation.yaml:Medaka alg2 p.G336* knock-in","focus_node_id":"node:disorder%3AALG2-Congenital_Disorder_of_Glycosylation:pathophysiology:Photoreceptor%20Maintenance%20Failure","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/ALG2-congenital_disorder_of_glycosylation.html#pathograph","nodes":[{"id":"model:kb/disorders/ALG2-Congenital_Disorder_of_Glycosylation.yaml:Medaka alg2 p.G336* knock-in","kind":"experimental_model","kind_label":"NAM model","label":"Medaka alg2 p.G336* knock-in","description":"A CRISPR knock-in medaka (Oryzias latipes) carrying a premature stop at the position orthologous to the index patient's c.1040delG allele. Homozygotes are normal through early embryogenesis and then decompensate shortly before hatching, dying 2-3 days post-hatch, which reproduces the human normal-at-birth, first-year-onset pattern in miniature.","url":"https://dismech.monarchinitiative.org/pages/disorders/ALG2-congenital_disorder_of_glycosylation.html#experimental-model-medaka-alg2-p-g336-knock-in","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AALG2-Congenital_Disorder_of_Glycosylation:pathophysiology:Photoreceptor%20Maintenance%20Failure","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Photoreceptor Maintenance Failure","description":"An engineered model of the index patient's allele loses rod photoreceptors progressively, with the phototransduction machinery massively under-represented at the protein level, giving retinitis pigmentosa. 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Wiring the node into the human chain in either direction would assert the translational claim the HUMAN_MODEL_MISMATCH discussion exists to hold open.","url":"https://dismech.monarchinitiative.org/pages/disorders/ALG2-congenital_disorder_of_glycosylation.html#pathophysiology-photoreceptor-maintenance-failure","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:1:model:kb/disorders/ALG2-Congenital_Disorder_of_Glycosylation.yaml:Medaka alg2 p.G336* knock-in","source_id":"model:kb/disorders/ALG2-Congenital_Disorder_of_Glycosylation.yaml:Medaka alg2 p.G336* knock-in","target_id":"node:disorder%3AALG2-Congenital_Disorder_of_Glycosylation:pathophysiology:Photoreceptor%20Maintenance%20Failure","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[1]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"LOW","causal_link_type":null,"causal_link_type_label":null,"description":"Progressive rod loss with under-representation of phototransduction proteins. 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This cardiometabolic state is the initiating context that distinguishes MASLD from other steatotic liver diseases.","url":"https://dismech.monarchinitiative.org/pages/disorders/Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease.html#pathophysiology-cardiometabolic-dysfunction-and-adipose-insulin-resistance","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMetabolic_Dysfunction-Associated_Steatotic_Liver_Disease:pathophysiology:Hepatocyte%20Lipid%20Overload","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Hepatocyte Lipid Overload","description":"Hepatocyte triglyceride accumulates when fatty acid inflow from adipose lipolysis and diet, plus de novo lipogenesis, exceeds fatty acid oxidation and very-low-density lipoprotein export. 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This node is the hepatic limb of the endothelial arm; it is not on the canonical lipotoxic backbone and is grouped under the emerging sinusoidal_endothelial_dysfunction_masld hypothesis.","url":"https://dismech.monarchinitiative.org/pages/disorders/Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease.html#pathophysiology-liver-sinusoidal-endothelial-cell-dysfunction-and-capillarization","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMetabolic_Dysfunction-Associated_Steatotic_Liver_Disease:pathophysiology:Transporter-Mediated%20Hepatic%20Fatty%20Acid%20Uptake","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Transporter-Mediated Hepatic Fatty Acid Uptake","description":"Long-chain fatty acids delivered to the liver do not enter hepatocytes by passive diffusion alone. 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The node carries the emerging hepatic-uptake hypothesis and is not asserted as a required step in human disease.","url":"https://dismech.monarchinitiative.org/pages/disorders/Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease.html#pathophysiology-transporter-mediated-hepatic-fatty-acid-uptake","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease.yaml:Metabolically competent iPSC white adipose tissue microphysiological system (iADIPO-MPS)","source_id":"model:kb/disorders/Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease.yaml:Metabolically competent iPSC white adipose tissue microphysiological system (iADIPO-MPS)","target_id":"node:disorder%3AMetabolic_Dysfunction-Associated_Steatotic_Liver_Disease:pathophysiology:Cardiometabolic%20Dysfunction%20and%20Adipose%20Insulin%20Resistance","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Measures","directed":false,"relationship":"MEASURES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"Provides the calibrated human assay for the adipose insulin-sensitivity variable this node turns on, with a dynamic range the authors report as competent against in vivo and ex vivo comparators.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AMetabolic_Dysfunction-Associated_Steatotic_Liver_Disease:0:0","source_id":"node:disorder%3AMetabolic_Dysfunction-Associated_Steatotic_Liver_Disease:pathophysiology:Cardiometabolic%20Dysfunction%20and%20Adipose%20Insulin%20Resistance","target_id":"node:disorder%3AMetabolic_Dysfunction-Associated_Steatotic_Liver_Disease:pathophysiology:Hepatocyte%20Lipid%20Overload","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Adipose insulin resistance and overnutrition supply the fatty acid inflow and lipogenic drive that produce hepatocyte lipid accumulation.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AMetabolic_Dysfunction-Associated_Steatotic_Liver_Disease:0:2","source_id":"node:disorder%3AMetabolic_Dysfunction-Associated_Steatotic_Liver_Disease:pathophysiology:Cardiometabolic%20Dysfunction%20and%20Adipose%20Insulin%20Resistance","target_id":"node:disorder%3AMetabolic_Dysfunction-Associated_Steatotic_Liver_Disease:pathophysiology:Liver%20Sinusoidal%20Endothelial%20Cell%20Dysfunction%20and%20Capillarization","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[2]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"The same cardiometabolic state that drives hepatocyte lipid loading also acts on the sinusoidal endothelium: insulin resistance and dyslipidaemia exacerbate endothelial activation and lipid handling across vascular and hepatic beds. This edge is what makes the endothelial arm a branch of the shared cardiometabolic trigger rather than a second, unexplained initiating step.","intermediate_mechanisms":[],"hypothesis_groups":["sinusoidal_endothelial_dysfunction_masld"],"evidence_count":1},{"id":"causal:disorder%3AMetabolic_Dysfunction-Associated_Steatotic_Liver_Disease:0:1","source_id":"node:disorder%3AMetabolic_Dysfunction-Associated_Steatotic_Liver_Disease:pathophysiology:Cardiometabolic%20Dysfunction%20and%20Adipose%20Insulin%20Resistance","target_id":"node:disorder%3AMetabolic_Dysfunction-Associated_Steatotic_Liver_Disease:pathophysiology:Transporter-Mediated%20Hepatic%20Fatty%20Acid%20Uptake","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[1]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Unrestrained adipose lipolysis raises the non-esterified fatty acid load presented to the liver, and the transporters at the hepatocyte basal membrane are what convert that circulating load into hepatocellular fatty acid entry. The edge asserts substrate delivery to the transport step, not upregulation of the transporters themselves.","intermediate_mechanisms":[],"hypothesis_groups":["hepatic_fatty_acid_uptake_masld"],"evidence_count":2}]}}],"mechanism_names":["Cardiometabolic Dysfunction and Adipose Insulin Resistance"],"relationships":["Measures"],"fidelities":["Moderate"],"biological_scales":["Organism"],"system_context_sources":["Model-level tissue","Model-level cell type","Linked mechanism cell type","Linked mechanism biological scale"],"modeled_system_labels":["white adipose tissue","white adipocyte","adipocyte","hepatocyte","Organism"],"biological_process_terms":[{"id":"GO:0032869","label":"cellular response to insulin stimulus","display_label":"cellular response to insulin stimulus","url":"http://purl.obolibrary.org/obo/GO_0032869"}],"biological_processes":["cellular response to insulin stimulus"],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":["Insulin-stimulated glucose uptake, fatty acid uptake and lipolysis suppression"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:34761526","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/34761526","reference_title":"Probing Insulin Sensitivity with Metabolically Competent Human Stem Cell-Derived White Adipose Tissue Microphysiological Systems.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Surprisingly, previously reported WAT differentiation approaches create insulin resistant WAT ill-suited for type-2 diabetes mellitus drug discovery.","explanation":"The negative platform result that makes this model informative for the node: an adipose model must be shown insulin-sensitive at baseline before a loss of insulin sensitivity can be attributed to a disease manipulation."},{"reference":"PMID:34761526","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/34761526","reference_title":"Probing Insulin Sensitivity with Metabolically Competent Human Stem Cell-Derived White Adipose Tissue Microphysiological Systems.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Using three independent insulin sensitivity assays, i.e., glucose and fatty acid uptake and suppression of lipolysis, as the functional readouts new differentiation conditions yielding hormonally responsive iADIPO are derived.","explanation":"Names the three functional readouts and the fact that they are what the differentiation conditions were selected against."}],"evidence_text":["Surprisingly, previously reported WAT differentiation approaches create insulin resistant WAT ill-suited for type-2 diabetes mellitus drug discovery.","Using three independent insulin sensitivity assays, i.e., glucose and fatty acid uptake and suppression of lipolysis, as the functional readouts new differentiation conditions yielding hormonally responsive iADIPO are derived.","The negative platform result that makes this model informative for the node: an adipose model must be shown insulin-sensitive at baseline before a loss of insulin sensitivity can be attributed to a disease manipulation.","Names the three functional readouts and the fact that they are what the differentiation conditions were selected against."],"evidence_status":"Evidence recorded","metadata_completeness":100,"metadata_present":["Model category","NAMO class","Organism","Anatomy","Cell type","Cell source","Culture system","Modeled mechanism","Publication","Evidence"],"metadata_missing":[],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease.html#experimental-model-metabolically-competent-ipsc-white-adipose-tissue-microphysiological-system-iadipo-mps","source_anchor":"experimental-model-metabolically-competent-ipsc-white-adipose-tissue-microphysiological-system-iadipo-mps"},{"id":"model:kb/disorders/Type_2_Diabetes_Mellitus.yaml:Metabolically competent iPSC white adipose tissue microphysiological system (iADIPO-MPS)","name":"Metabolically competent iPSC white adipose tissue microphysiological system (iADIPO-MPS)","description":"A New Approach Methodology built specifically because animal models and murine preadipocyte lines were poor substrates for type 2 diabetes drug discovery. 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Revised conditions plus chip optimization gave hormonally responsive tissue with larger, more unilocular lipid droplets and a dynamic range the authors report as competent against in vivo and ex vivo comparators, wide enough to identify both insulin sensitizers and desensitizers.","notes":null,"context_id":"disorder:Type_2_Diabetes_Mellitus","context_kind":"Disorder","disease_name":"Type 2 Diabetes Mellitus","disease_synonyms":[],"disease_term":{"id":"MONDO:0005148","label":"type 2 diabetes mellitus","display_label":"type 2 diabetes mellitus","url":"http://purl.obolibrary.org/obo/MONDO_0005148"},"experimental_model_type":"ORGAN_ON_CHIP","experimental_model_type_label":"Organ-on-chip","namo_type":"namo:OrganOnChip","declared_namo_class_name":"OrganOnChip","namo_class_name":"OrganOnChip","namo_class_label":"Organ On Chip","namo_description":"A model system that simulates the physiological functions of an organ using a microfluidic device. Examples: Airway-on-chip, ... Aligned with ISO 10991:2023 microfluidics terminology.","namo_docs_url":"https://monarch-initiative.github.io/namo/elements/OrganOnChip/","namo_ontology_url":"https://w3id.org/monarch-initiative/namo/OrganOnChip","namo_mapping_basis":"Explicit in DisMech","namo_class_in_schema":true,"namo_schema_status":"Defined in NAMO schema used for this build","modality":"Microphysiological system","organism":{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},"organism_label":"Homo sapiens","model_tissue":[{"id":"UBERON:0001347","label":"white adipose tissue","display_label":"white adipose tissue","url":"http://purl.obolibrary.org/obo/UBERON_0001347"}],"model_tissue_labels":["white adipose tissue"],"linked_anatomy":[{"id":"UBERON:0001347","label":"white adipose tissue","display_label":"White Adipose Tissue","url":"http://purl.obolibrary.org/obo/UBERON_0001347"}],"linked_anatomy_labels":["white adipose tissue"],"anatomy":[{"id":"UBERON:0001347","label":"white adipose tissue","display_label":"white adipose tissue","url":"http://purl.obolibrary.org/obo/UBERON_0001347"}],"anatomy_labels":["white adipose tissue"],"tissue_label":"white adipose tissue","model_cell_types":[{"id":"CL:0000448","label":"white adipocyte","display_label":"iPSC-derived white adipocyte (iADIPO)","url":"http://purl.obolibrary.org/obo/CL_0000448"}],"model_cell_type_labels":["white adipocyte"],"linked_cell_types":[{"id":"CL:0000182","label":"hepatocyte","display_label":"Hepatocyte","url":"http://purl.obolibrary.org/obo/CL_0000182"},{"id":"CL:0000188","label":"cell of skeletal muscle","display_label":"Skeletal Muscle Cell","url":"http://purl.obolibrary.org/obo/CL_0000188"},{"id":"CL:0000136","label":"adipocyte","display_label":"Adipocyte","url":"http://purl.obolibrary.org/obo/CL_0000136"},{"id":"CL:0000448","label":"white adipocyte","display_label":"White Adipocyte","url":"http://purl.obolibrary.org/obo/CL_0000448"}],"linked_cell_type_labels":["hepatocyte","cell of skeletal muscle","adipocyte","white adipocyte"],"cell_types":[{"id":"CL:0000448","label":"white adipocyte","display_label":"iPSC-derived white adipocyte (iADIPO)","url":"http://purl.obolibrary.org/obo/CL_0000448"},{"id":"CL:0000182","label":"hepatocyte","display_label":"Hepatocyte","url":"http://purl.obolibrary.org/obo/CL_0000182"},{"id":"CL:0000188","label":"cell of skeletal muscle","display_label":"Skeletal Muscle Cell","url":"http://purl.obolibrary.org/obo/CL_0000188"},{"id":"CL:0000136","label":"adipocyte","display_label":"Adipocyte","url":"http://purl.obolibrary.org/obo/CL_0000136"}],"cell_type_labels":["white adipocyte","hepatocyte","cell of skeletal muscle","adipocyte"],"conditions":["insulin-sensitive versus insulin-resistant human adipose tissue","insulin sensitizer and desensitizer pharmacology"],"cell_source":"Human pluripotent stem cell-derived white adipocytes","source_category":"Stem / progenitor-derived","culture_system":"Three-dimensional adipose tissue in a microphysiological system, benchmarked against two-dimensional culture","publication":"PMID:34761526","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34761526","mechanisms":[{"target":"Insulin Resistance","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Type_2_Diabetes_Mellitus.html#pathophysiology-insulin-resistance","relationship":"MEASURES","relationship_label":"Measures","fidelity":"MODERATE","fidelity_label":"Moderate","description":"Provides a calibrated human, non-animal assay for the adipose limb of this node, with the dynamic range needed to score a compound as sensitizing or desensitizing rather than merely to observe a resistant state.","limitations":"Adipose tissue alone, with no muscle, liver, islet or immune compartment, so it addresses one of the three tissues this node names. It is a healthy-tissue platform rather than a disease model: what it characterizes is a defect in prior differentiation protocols, not a defect in patients.","biological_scale":null,"anatomy":[],"cell_types":[{"id":"CL:0000182","label":"hepatocyte","display_label":"Hepatocyte","url":"http://purl.obolibrary.org/obo/CL_0000182"},{"id":"CL:0000188","label":"cell of skeletal muscle","display_label":"Skeletal Muscle Cell","url":"http://purl.obolibrary.org/obo/CL_0000188"},{"id":"CL:0000136","label":"adipocyte","display_label":"Adipocyte","url":"http://purl.obolibrary.org/obo/CL_0000136"}],"biological_processes":[{"id":"GO:0008286","label":"insulin receptor signaling pathway","display_label":"Insulin Signaling","url":"http://purl.obolibrary.org/obo/GO_0008286"}],"pathways":[],"genes":[{"id":"hgnc:9236","label":"PPARG","display_label":"PPARG","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/9236"}],"chemicals":[],"readouts":[{"name":"Insulin-stimulated glucose uptake, fatty acid uptake and lipolysis suppression","description":null,"target":"Insulin Resistance","direction":"INCREASED","interpretation":"Direction is relative to conventional two-dimensional culture, not to a disease state: the readouts record restored insulin responsiveness in the chip, which is the precondition for a later loss of responsiveness being interpretable as insulin resistance.","biological_processes":[{"id":"GO:0008286","label":"insulin receptor signaling pathway","display_label":"Insulin Receptor Signaling","url":"http://purl.obolibrary.org/obo/GO_0008286"}],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:34761526","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/34761526","reference_title":"Probing Insulin Sensitivity with Metabolically Competent Human Stem Cell-Derived White Adipose Tissue Microphysiological Systems.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Using three independent insulin sensitivity assays, i.e., glucose and fatty acid uptake and suppression of lipolysis, as the functional readouts new differentiation conditions yielding hormonally responsive iADIPO are derived.","explanation":"Names the three functional readouts and records that the differentiation conditions were selected against them rather than assumed to satisfy them."}],"notes":null}],"evidence":[{"reference":"PMID:34761526","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/34761526","reference_title":"Probing Insulin Sensitivity with Metabolically Competent Human Stem Cell-Derived White Adipose Tissue Microphysiological Systems.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Surprisingly, previously reported WAT differentiation approaches create insulin resistant WAT ill-suited for type-2 diabetes mellitus drug discovery.","explanation":"The negative platform result that makes this model informative for the node, and a caution for any curator reading an adipose insulin-resistance claim out of a stem-cell adipose model that has not been characterized this way."},{"reference":"PMID:34761526","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/34761526","reference_title":"Probing Insulin Sensitivity with Metabolically Competent Human Stem Cell-Derived White Adipose Tissue Microphysiological Systems.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Using three independent insulin sensitivity assays, i.e., glucose and fatty acid uptake and suppression of lipolysis, as the functional readouts new differentiation conditions yielding hormonally responsive iADIPO are derived.","explanation":"Names the three functional readouts and records that the differentiation conditions were selected against them rather than assumed to satisfy them."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Type_2_Diabetes_Mellitus","model_node_id":"model:kb/disorders/Type_2_Diabetes_Mellitus.yaml:Metabolically competent iPSC white adipose tissue microphysiological system (iADIPO-MPS)","focus_node_id":"node:disorder%3AType_2_Diabetes_Mellitus:pathophysiology:Insulin%20Resistance","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Type_2_Diabetes_Mellitus.html#pathograph","nodes":[{"id":"model:kb/disorders/Type_2_Diabetes_Mellitus.yaml:Metabolically competent iPSC white adipose tissue microphysiological system (iADIPO-MPS)","kind":"experimental_model","kind_label":"NAM model","label":"Metabolically competent iPSC white adipose tissue microphysiological system (iADIPO-MPS)","description":"A New Approach Methodology built specifically because animal models and murine preadipocyte lines were poor substrates for type 2 diabetes drug discovery. 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This leads to compensatory hyperinsulinemia and eventually beta cell exhaustion.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Type_2_Diabetes_Mellitus.html#pathophysiology-insulin-resistance","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AType_2_Diabetes_Mellitus:pathophysiology:Beta%20Cell%20Dysfunction","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Beta Cell Dysfunction","description":"Progressive loss of pancreatic beta cell function and mass leads to inadequate insulin secretion relative to insulin demand. Beta cell failure is the key determinant of disease progression.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Type_2_Diabetes_Mellitus.html#pathophysiology-beta-cell-dysfunction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AType_2_Diabetes_Mellitus:pathophysiology:Hepatic%20Glucose%20Overproduction","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Hepatic Glucose Overproduction","description":"Impaired suppression of hepatic gluconeogenesis leads to elevated fasting glucose levels. The liver fails to respond appropriately to insulin signals.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Type_2_Diabetes_Mellitus.html#pathophysiology-hepatic-glucose-overproduction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AType_2_Diabetes_Mellitus:pathophysiology:Impaired%20GLUT4-Mediated%20Glucose%20Uptake","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired GLUT4-Mediated Glucose Uptake","description":"Dysregulation of GLUT4 trafficking in adipocytes and skeletal muscle reduces insulin-stimulated glucose uptake. GULP1 facilitates GLUT4 translocation to the plasma membrane by counteracting ACAP1 inhibition of ARF6 activity. Reduced GULP1 activity therefore decreases peripheral glucose disposal and contributes to systemic insulin resistance. TBC1D4 is bound here as the human-genetic entry point to the same step: muscle biopsies show TBC1D4 and GLUT4 protein falling with increasing count of the common Greenlandic p.Arg684Ter allele, alongside severely decreased insulin-stimulated glucose uptake in muscle.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Type_2_Diabetes_Mellitus.html#pathophysiology-impaired-glut4-mediated-glucose-uptake","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AType_2_Diabetes_Mellitus:pathophysiology:White%20Adipose%20Tissue%20Inflammation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"White Adipose Tissue Inflammation","description":"With expanding adiposity, bone-marrow-derived macrophages accumulate in white adipose tissue, shift toward classical (M1) proinflammatory activation, and surround damaged adipocytes as crown-like structures. 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expression of extracellular matrix (ECM) components such as collagen I, collagen III, and fibronectin.","Treatment with the anti-fibrotic drug nintedanib reduced expression of ECM proteins and plasminogen activator inhibitor-1 (PAI-1), validating the system's utility for pharmacological testing.","Establishes the epithelial-fibroblast co-culture under breathing mechanics as the model configuration relevant to this node.","Reports the matrix-gene induction and its dependence on cyclic stretch.","Supports a drug-responsive expression surrogate for matrix deposition, without directly measuring accumulated cross-linked scar."],"evidence_status":"Evidence recorded","metadata_completeness":90,"metadata_present":["Model category","NAMO class","Organism","Anatomy","Cell type","Culture system","Modeled mechanism","Publication","Evidence"],"metadata_missing":["Cell source"],"dataset_context":"Available in same entry","context_dataset_ids":["dataset:ega:egas00001004758","dataset:ega:egas00001005794","dataset:geo:gse262882","dataset:geo:gse314583","dataset:massive:msv000093453","dataset:massive:msv000094806","dataset:massive:msv000098032","dataset:scea:e-curd-126"],"candidate_dataset_ids":[],"source_path":"kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Idiopathic_Pulmonary_Fibrosis.html#experimental-model-microengineered-alveolar-array-lung-on-chip-with-breathing-mechanics","source_anchor":"experimental-model-microengineered-alveolar-array-lung-on-chip-with-breathing-mechanics"},{"id":"model:kb/disorders/Optic_Atrophy_14.yaml:MID51 variant expression in HeLa cells","name":"MID51 variant expression in HeLa cells","description":"Transient expression of mCherry- or myc-tagged wild-type, p.Y240N and p.R146W MID51 in HeLa cells, assayed by live confocal microscopy for localisation, by immunoprecipitation and immunoblot for oligomerisation, and by photoactivatable matrix probe for fusion events. This is the entire functional evidence base for the disease, and it is the same system in which the independent group later mapped the DRP1-recruitment defect.","notes":null,"context_id":"disorder:Optic_Atrophy_14","context_kind":"Disorder","disease_name":"Optic Atrophy 14","disease_synonyms":["OPA14","MIEF1-related optic neuropathy","MID51-related dominant optic atrophy"],"disease_term":{"id":"MONDO:0957824","label":"optic atrophy 14","display_label":"Optic atrophy 14","url":"http://purl.obolibrary.org/obo/MONDO_0957824"},"experimental_model_type":"CELL_LINE","experimental_model_type_label":"Cell line","namo_type":"namo:CellLineModel","declared_namo_class_name":null,"namo_class_name":"CellLineModel","namo_class_label":"Cell Line Model","namo_description":"A model system based on immortalized cell lines that can be maintained in culture indefinitely. Examples: HepG2, A549, Caco-2, etc.","namo_docs_url":"https://monarch-initiative.github.io/namo/elements/CellLineModel/","namo_ontology_url":"https://w3id.org/monarch-initiative/namo/CellLineModel","namo_mapping_basis":"Safe mapping from DisMech category","namo_class_in_schema":true,"namo_schema_status":"Defined in NAMO schema used for this build","modality":"Cellular system","organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":null,"source_category":"Immortalized / cell line","culture_system":null,"publication":null,"publication_url":null,"mechanisms":[{"target":"Disrupted Mitochondrial Network Dynamics","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Optic_Atrophy_14.html#pathophysiology-disrupted-mitochondrial-network-dynamics","relationship":"RECAPITULATES","relationship_label":"Recapitulates","fidelity":"LOW","fidelity_label":"Low","description":"The assay demonstrates that both patient variants abolish MID51's normal effect on mitochondrial network dynamics, which is the disease's proposed cellular lesion.","limitations":"Three limitations, and they compound. The cell is a cervical adenocarcinoma line, not a retinal ganglion cell, and the selective vulnerability of that neuron is the whole unexplained part of the disease. The variants are expressed transiently from a plasmid on top of endogenous wild-type MID51 rather than from the endogenous locus, and the cited review states explicitly that heterologous overexpression and increased endogenous MiD have opposite effects on the network - so the assay's baseline is a condition that does not occur in a patient. And the readout is a difference from overexpressed wild-type MID51, not from an untransfected cell, which measures loss of an overexpression artefact's effect rather than the variant's effect on a normal cell. Fidelity is graded LOW on that basis.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0008053","label":"mitochondrial fusion","display_label":"mitochondrial fusion","url":"http://purl.obolibrary.org/obo/GO_0008053"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Mitochondrial fusion events after mito-PAGFP photoactivation","description":null,"target":"Disrupted Mitochondrial Network Dynamics","direction":"DECREASED","interpretation":"Both mutants gave significantly fewer fusion events than wild-type MID51, which is the quantitative basis for the disease's cellular claim.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:33632269","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33632269","reference_title":"Dominant mutations in MIEF1 affect mitochondrial dynamics and cause a singular late onset optic neuropathy.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"In contrast, both MID51 p.Y240N and p.R146W mutants resulted in significantly decreased mitochondrial fusion events and disrupted mitochondrial network dynamics, as compared to wild-type MID51 (Fig. 3j-m).","explanation":"The fusion-event measurement underlying this readout."}],"notes":null}],"evidence":[{"reference":"PMID:33632269","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33632269","reference_title":"Dominant mutations in MIEF1 affect mitochondrial dynamics and cause a singular late onset optic neuropathy.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Together, these results show that MIEF1 mutations linked to optic neuropathy preferentially disrupt the ability of MID51 to regulate mitochondrial fission/fusion dynamics.","explanation":"The authors' conclusion from this model, which is what makes it informative for this node."},{"reference":"PMID:33632269","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33632269","reference_title":"Dominant mutations in MIEF1 affect mitochondrial dynamics and cause a singular late onset optic neuropathy.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"In contrast, both MID51 p.Y240N and p.R146W mutants resulted in significantly decreased mitochondrial fusion events and disrupted mitochondrial network dynamics, as compared to wild-type MID51 (Fig. 3j-m).","explanation":"The fusion-event measurement underlying this readout."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Optic_Atrophy_14","model_node_id":"model:kb/disorders/Optic_Atrophy_14.yaml:MID51 variant expression in HeLa cells","focus_node_id":"node:disorder%3AOptic_Atrophy_14:pathophysiology:Disrupted%20Mitochondrial%20Network%20Dynamics","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Optic_Atrophy_14.html#pathograph","nodes":[{"id":"model:kb/disorders/Optic_Atrophy_14.yaml:MID51 variant expression in HeLa cells","kind":"experimental_model","kind_label":"NAM model","label":"MID51 variant expression in HeLa cells","description":"Transient expression of mCherry- or myc-tagged wild-type, p.Y240N and p.R146W MID51 in HeLa cells, assayed by live confocal microscopy for localisation, by immunoprecipitation and immunoblot for oligomerisation, and by photoactivatable matrix probe for fusion events. This is the entire functional evidence base for the disease, and it is the same system in which the independent group later mapped the DRP1-recruitment defect.","url":"https://dismech.monarchinitiative.org/pages/disorders/Optic_Atrophy_14.html#experimental-model-mid51-variant-expression-in-hela-cells","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AOptic_Atrophy_14:pathophysiology:Disrupted%20Mitochondrial%20Network%20Dynamics","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Disrupted Mitochondrial Network Dynamics","description":"The measured cellular phenotype, and the strongest evidence in the entity. Using a photoactivatable matrix probe to count fusion events between mitochondria in live cells, wild-type MID51 expression increased the rate of fusion, and both mutants significantly decreased it relative to wild-type.\nRead the direction carefully, because it is counterintuitive. MID51 is a *fission* adaptor, yet overexpressing wild-type MID51 increases *fusion* - the established explanation being that excess MID51 sequesters DRP1 in an inactive state on the outer membrane, so the net effect of more adaptor is less fission. The mutants fail to produce that effect. So what the assay measures directly is the loss of MID51's ability to modulate the network at all, not a shift toward either fission or fusion in the patient. The entry deliberately does not claim that patients' mitochondria are fragmented or elongated: nobody has looked at a patient's cells.","url":"https://dismech.monarchinitiative.org/pages/disorders/Optic_Atrophy_14.html#pathophysiology-disrupted-mitochondrial-network-dynamics","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3AOptic_Atrophy_14:pathophysiology:Impaired%20DRP1%20Recruitment%20to%20the%20Outer%20Mitochondrial%20Membrane","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired DRP1 Recruitment to the Outer Mitochondrial Membrane","description":"The proposed molecular lesion. MID51's job is to recruit DRP1, a dynamin-related GTPase that has no membrane-binding domain of its own, onto the outer mitochondrial membrane so that it can constrict and divide the organelle. The p.Y240 residue sits in the loop that binds DRP1, and independent work concludes that the p.Y240N variant disrupts DRP1 recruitment while leaving MID51 oligomerisation intact, with the downstream consequence of selectively inhibiting DRP1 GTP hydrolysis.\nMarked PROVISIONAL for a specific reason, not as a general hedge. The DRP1 recruitment claim is well evidenced for p.Y240N, whose position in the binding loop predicts it. It is *not* evidenced for p.R146W, which lies in a domain of unknown function outside the DRP1-binding region, and for which no DRP1 experiment has been reported. Both variants produce the same network phenotype at the node below, so either p.R146W reaches it by the same route for a reason nobody has identified, or the two alleles converge from different molecular starting points. Nothing published distinguishes these.","url":"https://dismech.monarchinitiative.org/pages/disorders/Optic_Atrophy_14.html#pathophysiology-impaired-drp1-recruitment-to-the-outer-mitochondrial-membrane","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3AOptic_Atrophy_14:pathophysiology:Retinal%20Ganglion%20Cell%20Degeneration%20and%20Optic%20Nerve%20Atrophy","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Retinal Ganglion Cell Degeneration and Optic Nerve Atrophy","description":"The clinical endpoint. Both patients had pale, moderately excavated optic disks with a normal retina, strongly abnormal visual evoked potentials, and - in the patient who had optical coherence tomography - retinal nerve fibre layer collapse in all quadrants of both eyes. The retinal nerve fibre layer is the retinal ganglion cell axon layer, so its loss is the closest available measurement of the cellular claim in this node's title.\nMarked PROVISIONAL because ganglion cell death itself is inferred, not observed: no tissue from a MIEF1 patient has been examined. What is observed is optic disc pallor plus axon-layer thinning plus conduction failure, which is the standard clinical basis for inferring ganglion cell loss in the inherited optic neuropathies.","url":"https://dismech.monarchinitiative.org/pages/disorders/Optic_Atrophy_14.html#pathophysiology-retinal-ganglion-cell-degeneration-and-optic-nerve-atrophy","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"}],"edges":[{"id":"model-link:0:model:kb/disorders/Optic_Atrophy_14.yaml:MID51 variant expression in HeLa cells","source_id":"model:kb/disorders/Optic_Atrophy_14.yaml:MID51 variant expression in HeLa cells","target_id":"node:disorder%3AOptic_Atrophy_14:pathophysiology:Disrupted%20Mitochondrial%20Network%20Dynamics","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"LOW","causal_link_type":null,"causal_link_type_label":null,"description":"The assay demonstrates that both patient variants abolish MID51's normal effect on mitochondrial network dynamics, which is the disease's proposed cellular lesion.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AOptic_Atrophy_14:3:0","source_id":"node:disorder%3AOptic_Atrophy_14:pathophysiology:Disrupted%20Mitochondrial%20Network%20Dynamics","target_id":"node:disorder%3AOptic_Atrophy_14:pathophysiology:Retinal%20Ganglion%20Cell%20Degeneration%20and%20Optic%20Nerve%20Atrophy","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[3].downstream[0]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"Why disrupted mitochondrial dynamics kills retinal ganglion cells in particular is the unsolved question of the whole dominant-optic-atrophy field, not a gap specific to MIEF1. No intermediate step has been demonstrated for this gene.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3AOptic_Atrophy_14:2:0","source_id":"node:disorder%3AOptic_Atrophy_14:pathophysiology:Impaired%20DRP1%20Recruitment%20to%20the%20Outer%20Mitochondrial%20Membrane","target_id":"node:disorder%3AOptic_Atrophy_14:pathophysiology:Disrupted%20Mitochondrial%20Network%20Dynamics","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0}]}},{"target":"Preserved MID51 Localisation and Oligomerisation","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Optic_Atrophy_14.html#pathophysiology-preserved-mid51-localisation-and-oligomerisation","relationship":"MEASURES","relationship_label":"Measures","fidelity":"MODERATE","fidelity_label":"Moderate","description":"The same system was used to test, and exclude, mislocalisation and oligomerisation defects. Graded MEASURES rather than RECAPITULATES because the informative result is a negative one: the model establishes that two candidate mechanisms are absent.","limitations":"A negative result in an overexpression system is weaker than a positive one, because excess wild-type protein could mask a partial folding or trafficking defect. The oligomerisation assay in particular scores tagged protein pulled down from a transfected cell, not the endogenous complex.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[],"biological_processes":[],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"MID51 oligomer to monomer ratio by immunoprecipitation","description":null,"target":"Preserved MID51 Localisation and Oligomerisation","direction":"UNCHANGED","interpretation":"Mutant and wild-type MID51 formed dimers, tetramers and high-molecular-weight species in similar ratios - a real negative result, recorded as such.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:33632269","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33632269","reference_title":"Dominant mutations in MIEF1 affect mitochondrial dynamics and cause a singular late onset optic neuropathy.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Similarly, we found that both mutant proteins MID51 p.Y240N (Fig. 3d-f) and MID51 p.R146W (Fig. 3g-i) also showed similar oligomerization patterns to wild-type MID51 (Fig. 3c), with similar ratios of each oligomeric species to monomer levels.","explanation":"The oligomerisation measurement underlying this readout."}],"notes":null}],"evidence":[{"reference":"PMID:33632269","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33632269","reference_title":"Dominant mutations in MIEF1 affect mitochondrial dynamics and cause a singular late onset optic neuropathy.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We next investigated whether MIEF1 variants disrupted the ability of MID51 to self-oligomerize.","explanation":"Establishes that the model was applied to this question, which is what makes its negative result usable."},{"reference":"PMID:33632269","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33632269","reference_title":"Dominant mutations in MIEF1 affect mitochondrial dynamics and cause a singular late onset optic neuropathy.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Similarly, we found that both mutant proteins MID51 p.Y240N (Fig. 3d-f) and MID51 p.R146W (Fig. 3g-i) also showed similar oligomerization patterns to wild-type MID51 (Fig. 3c), with similar ratios of each oligomeric species to monomer levels.","explanation":"The oligomerisation measurement underlying this readout."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Optic_Atrophy_14","model_node_id":"model:kb/disorders/Optic_Atrophy_14.yaml:MID51 variant expression in HeLa cells","focus_node_id":"node:disorder%3AOptic_Atrophy_14:pathophysiology:Preserved%20MID51%20Localisation%20and%20Oligomerisation","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Optic_Atrophy_14.html#pathograph","nodes":[{"id":"model:kb/disorders/Optic_Atrophy_14.yaml:MID51 variant expression in HeLa cells","kind":"experimental_model","kind_label":"NAM model","label":"MID51 variant expression in HeLa cells","description":"Transient expression of mCherry- or myc-tagged wild-type, p.Y240N and p.R146W MID51 in HeLa cells, assayed by live confocal microscopy for localisation, by immunoprecipitation and immunoblot for oligomerisation, and by photoactivatable matrix probe for fusion events. This is the entire functional evidence base for the disease, and it is the same system in which the independent group later mapped the DRP1-recruitment defect.","url":"https://dismech.monarchinitiative.org/pages/disorders/Optic_Atrophy_14.html#experimental-model-mid51-variant-expression-in-hela-cells","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AOptic_Atrophy_14:pathophysiology:Preserved%20MID51%20Localisation%20and%20Oligomerisation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Preserved MID51 Localisation and Oligomerisation","description":"A node that records what the disease is not, because two obvious mechanisms were tested and excluded, and excluding them is what makes the positive finding meaningful.\nBoth mutant proteins localise to the mitochondrial network in live cells just as wild-type MID51 does, so this is not a mislocalisation disease. Both form dimers, tetramers and high-molecular-weight species in the same ratios as wild-type, so it is not an oligomerisation disease either. A curator adding to this entry should not later attach a mislocalisation or misassembly mechanism to it without new data; these were looked for and were not there.\nAn independent group extended the second of those negatives one step downstream. MID51's other job, in complex with Fis1, is to drive lysosomal untethering at mitochondria-lysosome contact sites, and that function depends on the oligomerisation interface rather than on DRP1 binding. The optic-atrophy variant p.Y240N leaves it intact: it still forms a Mid51/Fis1 complex and does not misregulate lysosomal untethering or lysosomal network dynamics. So the preservation established here is not an incidental in vitro observation - it has a measurable functional consequence, and it is what makes the disease's lesion specific rather than general. Whether that specificity explains why the disease is confined to the optic nerve is an open question below.","url":"https://dismech.monarchinitiative.org/pages/disorders/Optic_Atrophy_14.html#pathophysiology-preserved-mid51-localisation-and-oligomerisation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3AOptic_Atrophy_14:pathophysiology:Heterozygous%20MIEF1%20Missense%20Variant","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Heterozygous MIEF1 Missense Variant","description":"Two variants, one per patient. c.718T>A gives p.Y240N, which lies in MID51's DRP1-binding region; c.436C>T gives p.R146W, in a domain conserved with MID49 but of no known function. Neither is in the transmembrane domain that anchors MID51 in the outer membrane, and neither is at a residue previously shown to mediate oligomerisation - which is what makes the functional results below interpretable rather than merely negative.\nMarked PROVISIONAL rather than ESTABLISHED because the pathogenicity argument is rarity plus in silico prediction plus an in vitro effect, in two unrelated singletons. The p.Y240N variant is absent from databases; p.R146W is rs778124994 at a gnomAD frequency of about 2 in 100,000, which is rare but not private.","url":"https://dismech.monarchinitiative.org/pages/disorders/Optic_Atrophy_14.html#pathophysiology-heterozygous-mief1-missense-variant","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"}],"edges":[{"id":"model-link:1:model:kb/disorders/Optic_Atrophy_14.yaml:MID51 variant expression in HeLa cells","source_id":"model:kb/disorders/Optic_Atrophy_14.yaml:MID51 variant expression in HeLa cells","target_id":"node:disorder%3AOptic_Atrophy_14:pathophysiology:Preserved%20MID51%20Localisation%20and%20Oligomerisation","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[1]","label":"Measures","directed":false,"relationship":"MEASURES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"The same system was used to test, and exclude, mislocalisation and oligomerisation defects. Graded MEASURES rather than RECAPITULATES because the informative result is a negative one: the model establishes that two candidate mechanisms are absent.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AOptic_Atrophy_14:0:0","source_id":"node:disorder%3AOptic_Atrophy_14:pathophysiology:Heterozygous%20MIEF1%20Missense%20Variant","target_id":"node:disorder%3AOptic_Atrophy_14:pathophysiology:Preserved%20MID51%20Localisation%20and%20Oligomerisation","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0}]}}],"mechanism_names":["Disrupted Mitochondrial Network Dynamics","Preserved MID51 Localisation and 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immunoprecipitation"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:33632269","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33632269","reference_title":"Dominant mutations in MIEF1 affect mitochondrial dynamics and cause a singular late onset optic neuropathy.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Together, these results show that MIEF1 mutations linked to optic neuropathy preferentially disrupt the ability of MID51 to regulate mitochondrial fission/fusion dynamics.","explanation":"The authors' conclusion from this model, which is what makes it informative for this node."},{"reference":"PMID:33632269","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33632269","reference_title":"Dominant mutations in MIEF1 affect mitochondrial dynamics and cause a singular late onset optic neuropathy.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"In contrast, both MID51 p.Y240N and p.R146W mutants resulted in significantly decreased mitochondrial fusion events and disrupted mitochondrial network dynamics, as compared to wild-type MID51 (Fig. 3j-m).","explanation":"The fusion-event measurement underlying this readout."},{"reference":"PMID:33632269","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33632269","reference_title":"Dominant mutations in MIEF1 affect mitochondrial dynamics and cause a singular late onset optic neuropathy.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We next investigated whether MIEF1 variants disrupted the ability of MID51 to self-oligomerize.","explanation":"Establishes that the model was applied to this question, which is what makes its negative result usable."},{"reference":"PMID:33632269","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33632269","reference_title":"Dominant mutations in MIEF1 affect 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In NEK1-knockout cells, both wild-type and kinase-dead NEK1 restored CFAP410 abundance, whereas association-defective variants did not; kinase activity and complex-dependent abundance are therefore separable requirements.","url":"https://dismech.monarchinitiative.org/pages/disorders/Axial_Spondylometaphyseal_Dysplasia.html#pathophysiology-disruption-of-the-cfap410-nek1-complex","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAxial_Spondylometaphyseal_Dysplasia:pathophysiology:Photoreceptor%20Connecting%20Cilium%20Dysfunction","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Photoreceptor Connecting Cilium Dysfunction","description":"CFAP410 localizes to the connecting cilium and basal-body structures of photoreceptors. 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Clinical gene-validity grades differ and should not be inferred from inclusion in one functional study.","url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Ciliary_Dyskinesia.html#pathophysiology-central-apparatus-transport-dysfunction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3APrimary_Ciliary_Dyskinesia:pathophysiology:Chronic%20Airway%20Infection%20and%20Neutrophilic%20Inflammation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Chronic Airway Infection and Neutrophilic Inflammation","description":"Retained secretions favor persistent airway infection, neutrophil recruitment and protease/oxidative injury. 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this is not a clinical efficacy threshold."}],"evidence_text":["Mucociliary transport declined nonlinearly, with speeds dropping from ~56 μm/s (100% WT) to ~9 μm/s in 100% mutant cultures.","The preprint reports a nonlinear transport response to mixing wild-type and CCDC40-mutant cells; this is not a clinical efficacy threshold."],"evidence_status":"Evidence recorded","metadata_completeness":100,"metadata_present":["Model category","NAMO class","Organism","Anatomy","Cell type","Cell source","Culture system","Modeled mechanism","Publication","Evidence"],"metadata_missing":[],"dataset_context":"Available in same entry","context_dataset_ids":["dataset:geo:gse254100","dataset:geo:gse272189"],"candidate_dataset_ids":[],"source_path":"kb/disorders/Primary_Ciliary_Dyskinesia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Primary_Ciliary_Dyskinesia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Ciliary_Dyskinesia.html#experimental-model-mixed-wild-type-and-ccdc40-deficient-airway-epithelial-cultures","source_anchor":"experimental-model-mixed-wild-type-and-ccdc40-deficient-airway-epithelial-cultures"},{"id":"model:kb/disorders/KMT2B-Related_Dystonia.yaml:Mll2 (Kmt2b) conditional-knockout mouse embryonic stem cells","name":"Mll2 (Kmt2b) conditional-knockout mouse embryonic stem cells","description":"Mouse embryonic stem cells carrying a conditional Mll2 allele, the gene encoding KMT2B, in which the enzyme can be depleted and then re-expressed while the chromatin state and DNA methylation of a CpG island promoter are followed over time. 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In iPSC-derived motor neurons the axonal pathology is directly visible as shortened neurites, breakage and swellings.","url":"https://dismech.monarchinitiative.org/pages/disorders/Charcot-Marie-Tooth_Disease_Axonal_Type_2Z.html#pathophysiology-axonal-degeneration","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACharcot-Marie-Tooth_Disease_Axonal_Type_2Z:phenotype:Areflexia","kind":"phenotype","kind_label":"Phenotype","label":"Areflexia","description":null,"url":"https://dismech.monarchinitiative.org/pages/disorders/Charcot-Marie-Tooth_Disease_Axonal_Type_2Z.html#phenotype-areflexia","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACharcot-Marie-Tooth_Disease_Axonal_Type_2Z:phenotype:Distal%20amyotrophy","kind":"phenotype","kind_label":"Phenotype","label":"Distal amyotrophy","description":null,"url":"https://dismech.monarchinitiative.org/pages/disorders/Charcot-Marie-Tooth_Disease_Axonal_Type_2Z.html#phenotype-distal-amyotrophy","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACharcot-Marie-Tooth_Disease_Axonal_Type_2Z:phenotype:Distal%20muscle%20weakness","kind":"phenotype","kind_label":"Phenotype","label":"Distal muscle weakness","description":"Length-dependent distal weakness is the core presentation, progressing proximally over years to decades. In the Spanish cohort a scapuloperoneal, asymmetric pattern with early proximal upper-limb involvement was more common than the classic length-dependent one.\nThe VERY_FREQUENT band here rests on this feature being definitional rather than on a published fraction. No source reports a distal-weakness denominator for CMT2Z, because distal weakness is how a patient is ascertained as having an axonal CMT in the first place — every reported patient has it by construction. Distal amyotrophy, by contrast, is graded FREQUENT: it is neither definitional nor given a denominator in any located source.","url":"https://dismech.monarchinitiative.org/pages/disorders/Charcot-Marie-Tooth_Disease_Axonal_Type_2Z.html#phenotype-distal-muscle-weakness","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACharcot-Marie-Tooth_Disease_Axonal_Type_2Z:phenotype:Fasciculations","kind":"phenotype","kind_label":"Phenotype","label":"Fasciculations","description":"Spontaneous motor-unit activity — fasciculations and myokymia — is frequent and is part of what makes the electrophysiological pattern distinctive.","url":"https://dismech.monarchinitiative.org/pages/disorders/Charcot-Marie-Tooth_Disease_Axonal_Type_2Z.html#phenotype-fasciculations","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACharcot-Marie-Tooth_Disease_Axonal_Type_2Z:pathophysiology:Impaired%20PARP1-Dependent%20DNA%20Repair","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired PARP1-Dependent DNA Repair","description":"MORC2 relaxes chromatin to facilitate double-strand break repair. In iPSC-derived motor neurons carrying three different MORC2 alleles, the mutants disrupt the MORC2-PARP1 interaction, reducing PARP1 activity and expression and the recruitment of downstream repair proteins, with accumulating DNA damage and apoptosis. This branch is a second, more recent account of how a chromatin gene kills axons, and it comes with a candidate intervention: blocking PAR degradation restored PAR levels and improved axonal pathology in the p.Ser87Leu neurons.","url":"https://dismech.monarchinitiative.org/pages/disorders/Charcot-Marie-Tooth_Disease_Axonal_Type_2Z.html#pathophysiology-impaired-parp1-dependent-dna-repair","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACharcot-Marie-Tooth_Disease_Axonal_Type_2Z:pathophysiology:Neuronal%20Transcriptional%20Dysregulation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Neuronal Transcriptional Dysregulation","description":"Mutant MORC2 changes gene expression in patient fibroblasts and in neurons, and the magnitude of that change tracks clinical severity: the p.Ser87Leu allele, associated with the most severe phenotype, produced more pronounced transcriptional change and abnormal axonal morphology than p.Arg252Trp in the same experimental system. MORC2 is highly expressed in human embryonic and adult neural tissue and its murine orthologue is developmentally regulated, which is the proposed reason a ubiquitously expressed chromatin gene produces a neuron-selective disease.","url":"https://dismech.monarchinitiative.org/pages/disorders/Charcot-Marie-Tooth_Disease_Axonal_Type_2Z.html#pathophysiology-neuronal-transcriptional-dysregulation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACharcot-Marie-Tooth_Disease_Axonal_Type_2Z:phenotype:Pes%20cavus","kind":"phenotype","kind_label":"Phenotype","label":"Pes 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It cannot speak to the residual-activity question that governs severity in patients.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0032543","label":"mitochondrial translation","display_label":"mitochondrial translation","url":"http://purl.obolibrary.org/obo/GO_0032543"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Reactive oxygen species level","description":null,"target":"Deficient Mitochondrial Protein Synthesis","direction":"INCREASED","interpretation":"The only evidence in this entry for an oxidative-stress component; it is from mouse cells with a different subunit knocked down, not from GATC patients.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:24579914","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/24579914","reference_title":"Glutamyl-tRNAGln amidotransferase is essential for mammalian mitochondrial translation in vivo.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"As a result, interfered cells present an impairment of the oxidative phosphorylation system and a significant increase in ROS (reactive oxygen species) levels.","explanation":"The measurement underlying this readout."}],"notes":null}],"evidence":[{"reference":"PMID:24579914","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/24579914","reference_title":"Glutamyl-tRNAGln amidotransferase is essential for mammalian mitochondrial translation in vivo.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"we demonstrate that mgatA (mouse GatA) interference in mouse cells produces a strong defect in mitochondrial translation without affecting the stability of the newly synthesized proteins","explanation":"Establishes the translation defect on knockdown of a GatCAB subunit."},{"reference":"PMID:24579914","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/24579914","reference_title":"Glutamyl-tRNAGln amidotransferase is essential for mammalian mitochondrial translation in vivo.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"As a result, interfered cells present an impairment of the oxidative phosphorylation system and a significant increase in ROS (reactive oxygen species) levels.","explanation":"The measurement underlying this readout."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Combined_Oxidative_Phosphorylation_Deficiency_42","model_node_id":"model:kb/disorders/Combined_Oxidative_Phosphorylation_Deficiency_42.yaml:mouse GatA (Qrsl1) RNA interference cell model","focus_node_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_42:pathophysiology:Deficient%20Mitochondrial%20Protein%20Synthesis","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_oxidative_phosphorylation_deficiency_42.html#pathograph","nodes":[{"id":"model:kb/disorders/Combined_Oxidative_Phosphorylation_Deficiency_42.yaml:mouse GatA (Qrsl1) RNA interference cell model","kind":"experimental_model","kind_label":"NAM model","label":"mouse GatA (Qrsl1) RNA interference cell model","description":"Knockdown of mouse GatA in mouse cells, published four years before the human disorder was described. It is the source of two claims that the patient data do not supply: that GatCAB loss raises reactive oxygen species, and that mischarged Glu-mt-tRNA(Gln) is rejected by the translation apparatus rather than being incorporated as glutamate.","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_oxidative_phosphorylation_deficiency_42.html#experimental-model-mouse-gata-qrsl1-rna-interference-cell-model","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_42:pathophysiology:Deficient%20Mitochondrial%20Protein%20Synthesis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Deficient Mitochondrial Protein Synthesis","description":"Pulse labelling with radiolabelled methionine in the presence of emetine, to silence cytoplasmic translation, showed a strong and generalized defect in mtDNA-encoded protein synthesis in the GATC patient's fibroblasts. Because glutamine codons occur throughout the thirteen mtDNA-encoded proteins, the defect is general rather than selective for one complex - this is the reason the disease is a combined rather than an isolated respiratory chain deficiency.\nA subtlety worth preserving: the reduction in newly synthesized protein was not accompanied by reduced steady-state levels of assembled OXPHOS subunits in fibroblasts. Chloramphenicol chase experiments showed the explanation is increased stability of the existing subunits, which together with residual GatCAB activity masks the defect in that cell type. A chloramphenicol block and release experiment made the kinetics visible: translation resumes at a near-normal rate for a few hours on accumulated charged tRNA, then falls behind as charging fails to keep up with demand.","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_oxidative_phosphorylation_deficiency_42.html#pathophysiology-deficient-mitochondrial-protein-synthesis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_42:pathophysiology:Combined%20Respiratory%20Chain%20Enzyme%20Deficiency","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Combined Respiratory Chain Enzyme Deficiency","description":"All patients showed a combined deficiency with decreased activities of complexes I and IV and low or borderline-low complex III, varying between tissues. 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The module's upstream node - age-related mitochondrial damage and mtDNA mutation - does not apply to a primary nuclear-gene translation defect, which is why conformance is declared at this node alone.","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_oxidative_phosphorylation_deficiency_42.html#pathophysiology-combined-respiratory-chain-enzyme-deficiency","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_42:pathophysiology:Impaired%20Transamidation%20of%20Glu-mt-tRNA%28Gln%29","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Transamidation of Glu-mt-tRNA(Gln)","description":"Mitochondria have no glutaminyl-tRNA synthetase. 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A normal-looking fibroblast assay run under standard conditions is therefore not evidence against the diagnosis.","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_oxidative_phosphorylation_deficiency_42.html#pathophysiology-impaired-transamidation-of-glu-mt-trna-gln","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"}],"edges":[{"id":"model-link:0:model:kb/disorders/Combined_Oxidative_Phosphorylation_Deficiency_42.yaml:mouse GatA (Qrsl1) RNA interference cell model","source_id":"model:kb/disorders/Combined_Oxidative_Phosphorylation_Deficiency_42.yaml:mouse GatA (Qrsl1) RNA interference cell 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Risk estimates vary with phenotype, age, gonadal histology, ascertainment and prior gonadectomy. TSPY and DDX3Y are candidate susceptibility genes expressed in affected germ cells, but their expression also occurs in nonmalignant cells and does not establish sufficiency for transformation.","url":"https://dismech.monarchinitiative.org/pages/disorders/45,X_46,XY_Mixed_Gonadal_Dysgenesis.html#pathophysiology-germ-cell-neoplasia-in-dysgenetic-gonads","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3A45_X_46_XY_Mixed_Gonadal_Dysgenesis:pathophysiology:Impaired%20Pubertal%20Sertoli%20Cell%20Function","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Pubertal Sertoli Cell Function","description":"Low inhibin B and rising FSH indicate impaired Sertoli-cell function in some individuals during or after puberty. Spontaneous pubertal onset and Sertoli dysfunction can coexist; gonadotropin or inhibin measurements do not by themselves demonstrate universal Leydig-cell failure.","url":"https://dismech.monarchinitiative.org/pages/disorders/45,X_46,XY_Mixed_Gonadal_Dysgenesis.html#pathophysiology-impaired-pubertal-sertoli-cell-function","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3A45_X_46_XY_Mixed_Gonadal_Dysgenesis:pathophysiology:Impaired%20Spermatogenesis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Spermatogenesis","description":"Germ-cell maturation is impaired in some dysgenetic testes. A multicenter male cohort found both focal and arrested spermatogenesis, while some men retained motile sperm. Histologic observations and semen results came from different assessed subsets; neither establishes complete absence of fertility potential throughout the mosaic population.","url":"https://dismech.monarchinitiative.org/pages/disorders/45,X_46,XY_Mixed_Gonadal_Dysgenesis.html#pathophysiology-impaired-spermatogenesis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3A45_X_46_XY_Mixed_Gonadal_Dysgenesis:pathophysiology:Reduced%20Leydig%20Cell%20Testosterone%20Production","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced Leydig Cell Testosterone Production","description":"Leydig-cell steroidogenic function can be reduced in dysgenetic testes. Basal and stimulated testosterone values vary with age and retained gonadal tissue. 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This is the model that establishes causality in this disease, and it is a rescue rather than a knockdown, so it tests the patients' own alleles rather than a constructed one.","notes":"Overexpressing MRPS2 in control cells had no negative effect on translation or OXPHOS assembly, which is the dose control for the rescue arm and is worth knowing for anyone considering gene-replacement approaches in this pathway.","context_id":"disorder:Combined_Oxidative_Phosphorylation_Deficiency_36","context_kind":"Disorder","disease_name":"Combined Oxidative Phosphorylation Deficiency 36","disease_synonyms":["COXPD36","combined oxidative phosphorylation deficiency type 36","MRPS2 deficiency","MRPS2-related mitochondrial disease","mitochondrial ribosomal protein S2 deficiency"],"disease_term":{"id":"MONDO:0054781","label":"combined oxidative phosphorylation deficiency 36","display_label":"combined oxidative phosphorylation deficiency 36","url":"http://purl.obolibrary.org/obo/MONDO_0054781"},"experimental_model_type":"PRIMARY_CELL_CULTURE","experimental_model_type_label":"Primary-cell culture","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":null,"source_category":"Primary / biopsy-derived","culture_system":null,"publication":null,"publication_url":null,"mechanisms":[{"target":"Inhibition of Mitochondrial Translation","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Oxidative_Phosphorylation_Deficiency_36.html#pathophysiology-inhibition-of-mitochondrial-translation","relationship":"RESCUES","relationship_label":"Rescues","fidelity":"HIGH","fidelity_label":"High","description":"Re-expressing wild-type MRPS2 partially restores mitochondrial translation in both patients' cells, and restores assembly of complexes I and IV.","limitations":"The restoration is partial rather than complete, and the readouts are steady-state abundance and pulse-labelled synthesis rather than respiratory flux or ATP output. A fibroblast is also not the cochlea, the liver or the brain, so the model speaks to the molecular step and not to any clinical feature.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0032543","label":"mitochondrial translation","display_label":"mitochondrial translation","url":"http://purl.obolibrary.org/obo/GO_0032543"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Pulse-labelled mitochondrial translation products","description":null,"target":"Inhibition of Mitochondrial Translation","direction":"RESTORED","interpretation":"Synthesis of mtDNA-encoded polypeptides recovers when wild-type MRPS2 is supplied, which is what makes the translation defect attributable to the MRPS2 alleles.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:29576219","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/29576219","reference_title":"Bi-allelic Mutations in the Mitochondrial Ribosomal Protein MRPS2 Cause Sensorineural Hearing Loss, Hypoglycemia, and Multiple OXPHOS Complex Deficiencies.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Pulse labeling of mitochondrial translation products demonstrates that the presence of wild-type MRPS2 partially restores mitochondrial translation in S1 and S2 fibroblasts.","explanation":"The measurement, with the authors' own qualifier that the restoration is partial."}],"notes":null}],"evidence":[{"reference":"PMID:29576219","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/29576219","reference_title":"Bi-allelic Mutations in the Mitochondrial Ribosomal Protein MRPS2 Cause Sensorineural Hearing Loss, Hypoglycemia, and Multiple OXPHOS Complex Deficiencies.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"To demonstrate the disease-causing nature of MRPS2 mutations, we carried out functional complementation experiments by generating control, S1, and S2 cell lines stably expressing either green fluorescent protein (GFP) as a negative control or wild-type MRPS2","explanation":"The design of the model, including the GFP control arm that makes the rescue interpretable."},{"reference":"PMID:29576219","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/29576219","reference_title":"Bi-allelic Mutations in the Mitochondrial Ribosomal Protein MRPS2 Cause Sensorineural Hearing Loss, Hypoglycemia, and Multiple OXPHOS Complex Deficiencies.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Pulse labeling of mitochondrial translation products demonstrates that the presence of wild-type MRPS2 partially restores mitochondrial translation in S1 and S2 fibroblasts.","explanation":"The measurement, with the authors' own qualifier that the restoration is partial."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Combined_Oxidative_Phosphorylation_Deficiency_36","model_node_id":"model:kb/disorders/Combined_Oxidative_Phosphorylation_Deficiency_36.yaml:MRPS2-complemented patient fibroblast lines","focus_node_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_36:pathophysiology:Inhibition%20of%20Mitochondrial%20Translation","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Oxidative_Phosphorylation_Deficiency_36.html#pathograph","nodes":[{"id":"model:kb/disorders/Combined_Oxidative_Phosphorylation_Deficiency_36.yaml:MRPS2-complemented patient fibroblast lines","kind":"experimental_model","kind_label":"NAM model","label":"MRPS2-complemented patient fibroblast lines","description":"Skin fibroblasts from both 2018 patients, transduced with a lentivirus expressing either wild-type MRPS2 or GFP as a negative control. This is the model that establishes causality in this disease, and it is a rescue rather than a knockdown, so it tests the patients' own alleles rather than a constructed one.","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Oxidative_Phosphorylation_Deficiency_36.html#experimental-model-mrps2-complemented-patient-fibroblast-lines","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_36:pathophysiology:Inhibition%20of%20Mitochondrial%20Translation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Inhibition of Mitochondrial Translation","description":"Pulse labelling of mitochondrial translation products with radiolabelled methionine and cysteine shows a profound and generalised defect in both patients' fibroblasts. Generalised is the operative word: it is not a subset of messages, which is what would be expected if MRPS2 retained the bacterial orthologue's message-selection function.","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Oxidative_Phosphorylation_Deficiency_36.html#pathophysiology-inhibition-of-mitochondrial-translation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_36:pathophysiology:Combined%20Deficiency%20of%20OXPHOS%20Complexes%20I%20and%20IV","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Combined Deficiency of OXPHOS Complexes I and IV","description":"In fibroblasts, complexes I and IV are reduced, complex III and the nucleus-encoded complex II are not, and complex V is present at normal amount but with subcomplexes that do not occur in control cells. In tissue the picture is broader: multiple complexes are deficient in liver and muscle in the first patient, and in liver and fibroblasts with an isolated complex IV deficiency in muscle in the second.\nThat discrepancy between fibroblast and tissue, and between the two patients' muscle, is worth stating rather than smoothing over. It means a normal muscle respiratory-chain panel does not exclude the diagnosis, and it is the reason the entity is named for a combined deficiency even though any single biopsy may show something narrower.\nThis is the convergence point of the entry. Every systemic feature below is downstream of this node.","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Oxidative_Phosphorylation_Deficiency_36.html#pathophysiology-combined-deficiency-of-oxphos-complexes-i-and-iv","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_36:pathophysiology:Failure%20of%20Mitoribosomal%20Small%20Subunit%20Assembly","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Failure of Mitoribosomal Small Subunit Assembly","description":"The small subunit fails to form. Three measurements agree: the other small-subunit proteins MRPS5, MRPS18B and MRPS28 fall with MRPS2 while the large-subunit proteins MRPL37 and MRPL44 do not; the 12S rRNA that the small subunit is built around falls while 16S rRNA does not; and complexome profiling finds no fully assembled small subunit.\nThe roughly 300 kDa early subassembly containing MRPS16, MRPS17, MRPS18B, MRPS22, MRPS26, MRPS27 and MRPS34 survives in patient cells, at reduced level. That observation is what places MRPS2 late in the assembly pathway, and it is the mechanistic basis for the severity hypothesis recorded in this entry's discussions.","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Oxidative_Phosphorylation_Deficiency_36.html#pathophysiology-failure-of-mitoribosomal-small-subunit-assembly","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_36:pathophysiology:Loss%20of%20Mitochondrial%2012S%20Ribosomal%20RNA","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Loss of Mitochondrial 12S Ribosomal RNA","description":"12S rRNA, the RNA core of the small subunit, is specifically reduced in patient fibroblasts while 16S rRNA — the large subunit's RNA — is not. The same pattern is seen in the MRPS22-mutant control line, so it is a general consequence of small-subunit protein loss rather than something particular to MRPS2.\nThis node is drawn separately from the assembly failure because it is separately measured and because it is the quantity that differs between the two families: the compound heterozygote, whose substituted residues face the RNA, loses slightly more of it than the homozygote whose substituted residue sits at the subunit surface.","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Oxidative_Phosphorylation_Deficiency_36.html#pathophysiology-loss-of-mitochondrial-12s-ribosomal-rna","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"}],"edges":[{"id":"model-link:0:model:kb/disorders/Combined_Oxidative_Phosphorylation_Deficiency_36.yaml:MRPS2-complemented patient fibroblast lines","source_id":"model:kb/disorders/Combined_Oxidative_Phosphorylation_Deficiency_36.yaml:MRPS2-complemented patient fibroblast lines","target_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_36:pathophysiology:Inhibition%20of%20Mitochondrial%20Translation","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Rescues","directed":false,"relationship":"RESCUES","fidelity":"HIGH","causal_link_type":null,"causal_link_type_label":null,"description":"Re-expressing wild-type MRPS2 partially restores mitochondrial translation in both patients' cells, and restores assembly of complexes I and IV.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_36:2:1","source_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_36:pathophysiology:Failure%20of%20Mitoribosomal%20Small%20Subunit%20Assembly","target_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_36:pathophysiology:Inhibition%20of%20Mitochondrial%20Translation","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[1]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Without an assembled small subunit there is no functional monosome, so translation of the mtDNA-encoded messages stops.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_36:4:0","source_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_36:pathophysiology:Inhibition%20of%20Mitochondrial%20Translation","target_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_36:pathophysiology:Combined%20Deficiency%20of%20OXPHOS%20Complexes%20I%20and%20IV","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[4].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"The thirteen mtDNA-encoded polypeptides are all subunits of complexes I, III, IV and V, so a general translation failure starves those complexes of subunits while leaving complex II, which is entirely nucleus-encoded, intact.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_36:3:0","source_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_36:pathophysiology:Loss%20of%20Mitochondrial%2012S%20Ribosomal%20RNA","target_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_36:pathophysiology:Inhibition%20of%20Mitochondrial%20Translation","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[3].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"The 12S rRNA is the catalytic and structural core of the small subunit; losing it removes the decoding capacity of the mitoribosome.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0}]}}],"mechanism_names":["Inhibition of Mitochondrial Translation"],"relationships":["Rescues"],"fidelities":["High"],"biological_scales":["Molecular"],"system_context_sources":["Linked mechanism biological scale"],"modeled_system_labels":["Molecular"],"biological_process_terms":[{"id":"GO:0032543","label":"mitochondrial translation","display_label":"mitochondrial translation","url":"http://purl.obolibrary.org/obo/GO_0032543"}],"biological_processes":["mitochondrial translation"],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":["Pulse-labelled mitochondrial translation products"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:29576219","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/29576219","reference_title":"Bi-allelic Mutations in the Mitochondrial Ribosomal Protein MRPS2 Cause Sensorineural Hearing Loss, Hypoglycemia, and Multiple OXPHOS Complex Deficiencies.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"To demonstrate the disease-causing nature of MRPS2 mutations, we carried out functional complementation experiments by generating control, S1, and S2 cell lines stably expressing either green fluorescent protein (GFP) as a negative control or wild-type MRPS2","explanation":"The design of the model, including the GFP control arm that makes the rescue interpretable."},{"reference":"PMID:29576219","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/29576219","reference_title":"Bi-allelic Mutations in the Mitochondrial Ribosomal Protein MRPS2 Cause Sensorineural Hearing Loss, Hypoglycemia, and Multiple OXPHOS Complex Deficiencies.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Pulse labeling of mitochondrial translation products demonstrates that the presence of wild-type MRPS2 partially restores mitochondrial translation in S1 and S2 fibroblasts.","explanation":"The measurement, with the authors' own qualifier that the restoration is partial."}],"evidence_text":["To demonstrate the disease-causing nature of MRPS2 mutations, we carried out functional complementation experiments by generating control, S1, and S2 cell lines stably expressing either green fluorescent protein (GFP) as a negative control or wild-type MRPS2","Pulse labeling of mitochondrial translation products demonstrates that the presence of wild-type MRPS2 partially restores mitochondrial translation in S1 and S2 fibroblasts.","The design of the model, including the GFP control arm that makes the rescue interpretable.","The measurement, with the authors' own qualifier that the restoration is partial."],"evidence_status":"Evidence recorded","metadata_completeness":30,"metadata_present":["Model category","Modeled mechanism","Evidence"],"metadata_missing":["NAMO class","Organism","Anatomy","Cell type","Cell source","Culture system","Publication"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Combined_Oxidative_Phosphorylation_Deficiency_36.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Combined_Oxidative_Phosphorylation_Deficiency_36.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Oxidative_Phosphorylation_Deficiency_36.html#experimental-model-mrps2-complemented-patient-fibroblast-lines","source_anchor":"experimental-model-mrps2-complemented-patient-fibroblast-lines"},{"id":"model:kb/disorders/MTHFD1_Deficiency.yaml:MTHFD1-deficient patient fibroblasts","name":"MTHFD1-deficient patient fibroblasts","description":"Cultured skin fibroblasts from affected patients. Because homozygous Mthfd1 disruption is early embryonic lethal in mouse and the only available mouse line models the common R653Q polymorphism rather than this disease, patient fibroblasts are the sole system in which the mechanism of MTHFD1 deficiency has been measured. 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It is the closest thing to a human model system that exists for this entity, and testing it is the experiment ClinGen's Disputed classification is waiting on.","notes":null,"context_id":"disorder:Hypertrophic_Cardiomyopathy_14","context_kind":"Disorder","disease_name":"Hypertrophic Cardiomyopathy 14","disease_synonyms":["CMH14","MYH6 hypertrophic cardiomyopathy","alpha-myosin heavy chain hypertrophic cardiomyopathy","cardiomyopathy, familial hypertrophic, 14","cardiomyopathy, hypertrophic, 14","hypertrophic cardiomyopathy caused by mutation in MYH6"],"disease_term":{"id":"MONDO:0013197","label":"hypertrophic cardiomyopathy 14","display_label":"hypertrophic cardiomyopathy 14","url":"http://purl.obolibrary.org/obo/MONDO_0013197"},"experimental_model_type":"IPSC_DERIVED_MODEL","experimental_model_type_label":"iPSC-derived model","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},"organism_label":"Homo sapiens","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[{"id":"UBERON:0002349","label":"myocardium","display_label":"myocardium","url":"http://purl.obolibrary.org/obo/UBERON_0002349"}],"linked_anatomy_labels":["myocardium"],"anatomy":[{"id":"UBERON:0002349","label":"myocardium","display_label":"myocardium","url":"http://purl.obolibrary.org/obo/UBERON_0002349"}],"anatomy_labels":["myocardium"],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[{"id":"CL:0002131","label":"regular ventricular cardiac myocyte","display_label":"ventricular cardiomyocyte","url":"http://purl.obolibrary.org/obo/CL_0002131"}],"linked_cell_type_labels":["regular ventricular cardiac myocyte"],"cell_types":[{"id":"CL:0002131","label":"regular ventricular cardiac myocyte","display_label":"ventricular cardiomyocyte","url":"http://purl.obolibrary.org/obo/CL_0002131"}],"cell_type_labels":["regular ventricular cardiac myocyte"],"conditions":[],"cell_source":null,"source_category":"iPSC-derived","culture_system":null,"publication":null,"publication_url":null,"mechanisms":[{"target":"MYH6 Missense Variant in Alpha-Myosin Heavy Chain","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_14.html#pathophysiology-myh6-missense-variant-in-alpha-myosin-heavy-chain","relationship":"PERTURBS","relationship_label":"Perturbs","fidelity":"UNKNOWN","fidelity_label":"Unknown","description":"The line carries the patient's own heterozygous MYH6 allele in a human genetic background, so it reproduces the initiating lesion of this entry exactly.","limitations":"No differentiated-cardiomyocyte phenotype has been reported for this line — no contractility, sarcomere-organisation, or calcium-handling readout. It therefore establishes the lesion is modellable, not that it is pathogenic. Fidelity is UNKNOWN rather than HIGH for that reason.","biological_scale":"MOLECULAR","anatomy":[{"id":"UBERON:0002349","label":"myocardium","display_label":"myocardium","url":"http://purl.obolibrary.org/obo/UBERON_0002349"}],"cell_types":[{"id":"CL:0002131","label":"regular ventricular cardiac myocyte","display_label":"ventricular cardiomyocyte","url":"http://purl.obolibrary.org/obo/CL_0002131"}],"biological_processes":[],"pathways":[],"genes":[{"id":"hgnc:7576","label":"MYH6","display_label":"MYH6","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/7576"}],"chemicals":[],"readouts":[],"evidence":[{"reference":"PMID:33385793","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33385793","reference_title":"Generation of an IPSC line from a patient with hypertrophic cardiomyopathy carrying a mutation in MYH6 gene.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"An induced pluripotent stem cell (iPSC) line was generated from peripheral blood mononuclear cells (PBMCs) of a 41-year-old male patient with hypertrophic cardiomyopathy who carries a G3755A heterozygote mutation in the MYH6 gene.","explanation":"Establishes the existence and genotype of the line, and that it derives from an HCM patient carrying the MYH6 allele."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Hypertrophic_Cardiomyopathy_14","model_node_id":"model:kb/disorders/Hypertrophic_Cardiomyopathy_14.yaml:MYH6 c.G3755A patient-derived iPSC line","focus_node_id":"node:disorder%3AHypertrophic_Cardiomyopathy_14:pathophysiology:MYH6%20Missense%20Variant%20in%20Alpha-Myosin%20Heavy%20Chain","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_14.html#pathograph","nodes":[{"id":"model:kb/disorders/Hypertrophic_Cardiomyopathy_14.yaml:MYH6 c.G3755A patient-derived iPSC line","kind":"experimental_model","kind_label":"NAM model","label":"MYH6 c.G3755A patient-derived iPSC line","description":"An induced pluripotent stem cell line derived from peripheral blood mononuclear cells of a 41-year-old man with hypertrophic cardiomyopathy carrying a heterozygous MYH6 G3755A variant. 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It is the closest thing to a human model system that exists for this entity, and testing it is the experiment ClinGen's Disputed classification is waiting on.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_14.html#experimental-model-myh6-c-g3755a-patient-derived-ipsc-line","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_14:pathophysiology:MYH6%20Missense%20Variant%20in%20Alpha-Myosin%20Heavy%20Chain","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"MYH6 Missense Variant in Alpha-Myosin Heavy Chain","description":"The proposed initiating lesion in CMH14 is a heterozygous missense variant in MYH6, encoding the alpha-cardiac myosin heavy chain. Four unique missense alleles have been reported in HCM probands with limited pathogenicity evidence. The reported alleles fall in conserved residues and are predicted to change the structure or chemical bonding of the protein, but no functional assay of any HCM-attributed MYH6 allele has been reported, and this node is therefore an attributed lesion rather than a demonstrated one.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_14.html#pathophysiology-myh6-missense-variant-in-alpha-myosin-heavy-chain","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_14:pathophysiology:Altered%20Sarcomere%20Motor%20Function","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Altered Sarcomere Motor Function","description":"The hypothesised proximal consequence of an HCM-attributed MYH6 allele is a change in the actin-based motor behaviour of the affected myosin molecules within the ventricular sarcomere, by analogy with the well-characterised MYH7 missense alleles. This node carries no direct evidence for any human HCM-attributed MYH6 variant: no functional characterisation of such an allele has been published, which is one of the stated grounds for ClinGen's Disputed classification. It is retained as an explicit hypothesis node rather than dropped, so that the gap is visible and addressable.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_14.html#pathophysiology-altered-sarcomere-motor-function","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Hypertrophic_Cardiomyopathy_14.yaml:MYH6 c.G3755A patient-derived iPSC line","source_id":"model:kb/disorders/Hypertrophic_Cardiomyopathy_14.yaml:MYH6 c.G3755A patient-derived iPSC line","target_id":"node:disorder%3AHypertrophic_Cardiomyopathy_14:pathophysiology:MYH6%20Missense%20Variant%20in%20Alpha-Myosin%20Heavy%20Chain","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Perturbs","directed":false,"relationship":"PERTURBS","fidelity":"UNKNOWN","causal_link_type":null,"causal_link_type_label":null,"description":"The line carries the patient's own heterozygous MYH6 allele in a human genetic background, so it reproduces the initiating lesion of this entry exactly.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AHypertrophic_Cardiomyopathy_14:0:0","source_id":"node:disorder%3AHypertrophic_Cardiomyopathy_14:pathophysiology:MYH6%20Missense%20Variant%20in%20Alpha-Myosin%20Heavy%20Chain","target_id":"node:disorder%3AHypertrophic_Cardiomyopathy_14:pathophysiology:Altered%20Sarcomere%20Motor%20Function","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"The proposed proximal consequence, by analogy with MYH7 missense disease. Asserted by analogy, not measured for any MYH6 HCM allele.","intermediate_mechanisms":[],"hypothesis_groups":["myh6_minor_ventricular_isoform_hcm"],"evidence_count":1}]}}],"mechanism_names":["MYH6 Missense Variant in Alpha-Myosin Heavy Chain"],"relationships":["Perturbs"],"fidelities":["Unknown"],"biological_scales":["Molecular"],"system_context_sources":["Linked mechanism anatomy","Linked mechanism cell type","Linked mechanism biological scale"],"modeled_system_labels":["myocardium","regular ventricular cardiac myocyte","Molecular"],"biological_process_terms":[],"biological_processes":[],"pathway_terms":[],"pathways":[],"gene_terms":[{"id":"hgnc:7576","label":"MYH6","display_label":"MYH6","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/7576"}],"genes":["MYH6"],"chemical_terms":[],"chemicals":[],"readout_names":[],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:33385793","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33385793","reference_title":"Generation of an IPSC line from a patient with hypertrophic cardiomyopathy carrying a mutation in MYH6 gene.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The generated iPSC line expressed pluripotency markers, exhibited a normal karyotype, presented the specific mutation, and demonstrated differentiation potential into three germ layers in vitro.","explanation":"Characterises the line itself — pluripotency, karyotype, presence of the MYH6 variant, and trilineage differentiation capacity — which is what qualifies it as a usable model system for this entity."},{"reference":"PMID:33385793","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33385793","reference_title":"Generation of an IPSC line from a patient with hypertrophic cardiomyopathy carrying a mutation in MYH6 gene.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"An induced pluripotent stem cell (iPSC) line was generated from peripheral blood mononuclear cells (PBMCs) of a 41-year-old male patient with hypertrophic cardiomyopathy who carries a G3755A heterozygote mutation in the MYH6 gene.","explanation":"Establishes the existence and genotype of the line, and that it derives from an HCM patient carrying the MYH6 allele."}],"evidence_text":["The generated iPSC line expressed pluripotency markers, exhibited a normal karyotype, presented the specific mutation, and demonstrated differentiation potential into three germ layers in vitro.","An induced pluripotent stem cell (iPSC) line was generated from peripheral blood mononuclear cells (PBMCs) of a 41-year-old male patient with hypertrophic cardiomyopathy who carries a G3755A heterozygote mutation in the MYH6 gene.","Characterises the line itself — pluripotency, karyotype, presence of the MYH6 variant, and trilineage differentiation capacity — which is what qualifies it as a usable model system for this entity.","Establishes the existence and genotype of the line, and that it derives from an HCM patient carrying the MYH6 allele."],"evidence_status":"Evidence recorded","metadata_completeness":60,"metadata_present":["Model category","Organism","Anatomy","Cell type","Modeled mechanism","Evidence"],"metadata_missing":["NAMO class","Cell source","Culture system","Publication"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Hypertrophic_Cardiomyopathy_14.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hypertrophic_Cardiomyopathy_14.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_14.html#experimental-model-myh6-c-g3755a-patient-derived-ipsc-line","source_anchor":"experimental-model-myh6-c-g3755a-patient-derived-ipsc-line"},{"id":"model:kb/disorders/Hypertrophic_Cardiomyopathy_1.yaml:MYH7 G256E gene-edited hiPSC-cardiomyocyte multiscale platform","name":"MYH7 G256E gene-edited hiPSC-cardiomyocyte multiscale platform","description":"An isogenic gene-edited MYH7 WT/G256E hiPSC line characterised in parallel at purified-protein, myofibril, single-cell and engineered-heart-tissue level. 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Many MYH7 HCM mutations map to the interfaces that stabilize this folded-back state (the myosin mesa, the head-head and head-tail contacts), and they weaken those intramolecular interactions. The result is release of sequestered heads from the SRX/IHM into the disordered-relaxed state, so more heads become functionally accessible to actin — the molecular origin of hypercontractility shared across a large subset of MYH7 alleles.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_1.html#pathophysiology-destabilization-of-the-autoinhibited-super-relaxed-state","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Increased%20Motor%20Force%20and%20Energetic%20Cost","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Increased Motor Force and Energetic Cost","description":"Beyond releasing sequestered heads, individual MYH7 missense alleles alter the mechanochemistry of the motor stroke itself. Single-molecule and myofibril studies show mutation-specific changes — increased intrinsic force per cross-bridge, and faster cross-bridge detachment kinetics — that together raise the force generated by the ensemble of motors and increase the ATP consumed per unit tension (tension cost). The energetic penalty, measured directly in human myocardium carrying R403Q, is a distinctive feature of the beta-myosin motor lesion and links the molecular defect to the myocardial energy deficit seen in HCM.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_1.html#pathophysiology-increased-motor-force-and-energetic-cost","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:MYH7%20Missense%20Variant%20in%20Beta-Cardiac%20Myosin%20Heavy%20Chain","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"MYH7 Missense Variant in Beta-Cardiac Myosin Heavy Chain","description":"The initiating lesion in CMH1 is a heterozygous missense variant in MYH7, the gene encoding the beta-cardiac myosin heavy chain — the ATP-hydrolysing motor of the sarcomeric thick filament. The founding example, and still the archetype, is Arg403Gln (R403Q), the first mutation ever linked to familial hypertrophic cardiomyopathy; R403Q sits in the globular myosin head (S1), the region responsible for actin interaction and motor function. In contrast to the truncating, haploinsufficiency mechanism of MYBPC3 disease, most MYH7 alleles are missense changes that are stably expressed and incorporated into the sarcomere as a mutant motor, so the mutant protein perturbs contraction directly rather than by its absence.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_1.html#pathophysiology-myh7-missense-variant-in-beta-cardiac-myosin-heavy-chain","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Hypertrophic_Cardiomyopathy_1.yaml:MYH7 G256E gene-edited hiPSC-cardiomyocyte multiscale platform","source_id":"model:kb/disorders/Hypertrophic_Cardiomyopathy_1.yaml:MYH7 G256E gene-edited hiPSC-cardiomyocyte multiscale platform","target_id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Destabilization%20of%20the%20Autoinhibited%20Super-Relaxed%20State","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Measures","directed":false,"relationship":"MEASURES","fidelity":"HIGH","causal_link_type":null,"causal_link_type_label":null,"description":"Quantifies the folded-back myosin fraction directly for a named MYH7 allele, giving the node a measured effect size rather than a class claim.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3AHypertrophic_Cardiomyopathy_1:1:0","source_id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Destabilization%20of%20the%20Autoinhibited%20Super-Relaxed%20State","target_id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Increased%20Motor%20Force%20and%20Energetic%20Cost","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Heads released from the super-relaxed reserve, together with allele-specific changes in the motor stroke, raise ensemble force and the ATP cost of contraction.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3AHypertrophic_Cardiomyopathy_1:0:0","source_id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:MYH7%20Missense%20Variant%20in%20Beta-Cardiac%20Myosin%20Heavy%20Chain","target_id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Destabilization%20of%20the%20Autoinhibited%20Super-Relaxed%20State","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"The mutant motor, incorporated into the thick filament, destabilizes the folded-back autoinhibited state that normally sequesters myosin heads.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0}]}},{"target":"Sarcomere Hypercontractility with Impaired Relaxation","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_1.html#pathophysiology-sarcomere-hypercontractility-with-impaired-relaxation","relationship":"RECAPITULATES","relationship_label":"Recapitulates","fidelity":"MODERATE","fidelity_label":"Moderate","description":"Greater and faster tension development was reproduced in myofibrils, in single cells and in engineered heart tissue from the same edited line.","limitations":"G256E is an incompletely penetrant allele, so the cellular phenotype it produces is not automatically the phenotype of the more severe MYH7 alleles; and hiPSC-cardiomyocyte immaturity limits extrapolation of absolute contractile parameters to adult myocardium.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[{"id":"CL:0002131","label":"regular ventricular cardiac myocyte","display_label":"Ventricular cardiomyocyte","url":"http://purl.obolibrary.org/obo/CL_0002131"}],"biological_processes":[{"id":"GO:0086003","label":"cardiac muscle cell contraction","display_label":"Cardiac Muscle Cell Contraction","url":"http://purl.obolibrary.org/obo/GO_0086003"},{"id":"GO:0055117","label":"regulation of cardiac muscle contraction","display_label":"Regulation of Cardiac Muscle Contraction","url":"http://purl.obolibrary.org/obo/GO_0055117"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[],"evidence":[{"reference":"PMID:38683993","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38683993","reference_title":"Incomplete-penetrant hypertrophic cardiomyopathy MYH7 G256E mutation causes hypercontractility and elevated mitochondrial respiration.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Myofibrils from gene-edited MYH7WT/G256E human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) exhibited greater and faster tension development. This hypercontractile phenotype persisted in single-cell hiPSC-CMs and engineered heart tissues.","explanation":"Shows the hypercontractile phenotype holding across three scales in one isogenic system, which is what makes this model informative for the node rather than one more single-assay result."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Hypertrophic_Cardiomyopathy_1","model_node_id":"model:kb/disorders/Hypertrophic_Cardiomyopathy_1.yaml:MYH7 G256E gene-edited hiPSC-cardiomyocyte multiscale platform","focus_node_id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Sarcomere%20Hypercontractility%20with%20Impaired%20Relaxation","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_1.html#pathograph","nodes":[{"id":"model:kb/disorders/Hypertrophic_Cardiomyopathy_1.yaml:MYH7 G256E gene-edited hiPSC-cardiomyocyte multiscale platform","kind":"experimental_model","kind_label":"NAM model","label":"MYH7 G256E gene-edited hiPSC-cardiomyocyte multiscale platform","description":"An isogenic gene-edited MYH7 WT/G256E hiPSC line characterised in parallel at purified-protein, myofibril, single-cell and engineered-heart-tissue level. Its value for this entry is that it carries one allele through every scale of the mechanism chain at once, so the hypercontractility claim does not depend on any single assay — the failure mode the report itself flags for R403Q, where single-assay measurements have gone both ways.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_1.html#experimental-model-myh7-g256e-gene-edited-hipsc-cardiomyocyte-multiscale-platform","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Sarcomere%20Hypercontractility%20with%20Impaired%20Relaxation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Sarcomere Hypercontractility with Impaired Relaxation","description":"At the cell level the molecular changes converge on hypercontractility: CRISPR-edited human iPSC-derived cardiomyocytes carrying an MYH7 HCM mutation generate significantly greater contractile force than isogenic controls. Because the same lesion disturbs cross-bridge relaxation kinetics, systolic hypercontraction is accompanied by impaired diastolic relaxation. This hypercontractile, poorly relaxing cell state — a key pathophysiological abnormality of HCM and the determinant of dynamic outflow obstruction — is the cellular phenotype the cardiac myosin inhibitors were designed to normalize.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_1.html#pathophysiology-sarcomere-hypercontractility-with-impaired-relaxation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Cardiomyocyte-to-Fibroblast%20EGFR%20Paracrine%20Signaling","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Cardiomyocyte-to-Fibroblast EGFR Paracrine Signaling","description":"Interstitial fibrosis in CMH1 is not solely a passive response to wall stress. In engineered cardiac microtissues built from MYH7 R403Q hiPSC-derived cardiomyocytes co-cultured with wild-type ventricular cardiac fibroblasts, the mutant cardiomyocytes release paracrine factors that drive fibroblast proliferation and collagen deposition. Collagen I content rose 40% over isogenic wild-type microtissues and the tissue stiffened, and the effect depended on fibroblast proliferation rather than on cardiomyocyte matrix output. Epidermal growth factor alone was sufficient to stimulate the stromal cells, and inhibiting EGFR tyrosine kinase with erlotinib attenuated the activation — identifying EGFR signalling as the transducing arm and, in principle, a druggable one. The same microtissue system shows that the tissue-level consequence is hypocontractility even while the individual mutant cardiomyocytes are hypercontractile, which is how a cell-autonomous gain of contractile function ends up producing a stiff, poorly contracting ventricle.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_1.html#pathophysiology-cardiomyocyte-to-fibroblast-egfr-paracrine-signaling","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Cell-to-Cell%20Contractile%20Imbalance","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Cell-to-Cell Contractile Imbalance","description":"A mechanism specific to the missense/poison-peptide biology of MYH7 disease. Because the mutant and wild-type MYH7 alleles are transcribed in a random, burst-like fashion and independently of one another, the fraction of mutant beta-myosin varies markedly from cardiomyocyte to cardiomyocyte within a single patient's myocardium. This produces much greater cell-to-cell variability of contractile function than in control hearts. The resulting mechanical mismatch between adjacent, differently loaded myocytes is proposed to drive the myofiber disarray and interstitial fibrosis that are hallmarks of HCM, providing a route from the molecular lesion to the tissue phenotype that does not depend on the average level of hypercontractility alone.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_1.html#pathophysiology-cell-to-cell-contractile-imbalance","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Increased%20Motor%20Force%20and%20Energetic%20Cost","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Increased Motor Force and Energetic Cost","description":"Beyond releasing sequestered heads, individual MYH7 missense alleles alter the mechanochemistry of the motor stroke itself. Single-molecule and myofibril studies show mutation-specific changes — increased intrinsic force per cross-bridge, and faster cross-bridge detachment kinetics — that together raise the force generated by the ensemble of motors and increase the ATP consumed per unit tension (tension cost). The energetic penalty, measured directly in human myocardium carrying R403Q, is a distinctive feature of the beta-myosin motor lesion and links the molecular defect to the myocardial energy deficit seen in HCM.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_1.html#pathophysiology-increased-motor-force-and-energetic-cost","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Ventricular%20Hypertrophy%2C%20Myocyte%20Disarray%20and%20Fibrosis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Ventricular Hypertrophy, Myocyte Disarray and Fibrosis","description":"Chronic hypercontractility with raised energetic cost, amplified by cell-to-cell contractile imbalance, drives the structural remodeling that defines the clinical phenotype: cardiomyocyte hypertrophy — typically asymmetric and septal-predominant — together with myofiber disarray and interstitial and replacement fibrosis. Pro-hypertrophic growth signalling contributes: in an MYH7-mutant human iPSC-cardiomyocyte model, cellular hypertrophy was prevented by inhibition of ERK or Akt, implicating those pathways downstream of the mechanical stimulus. Fibrosis provides the substrate for both diastolic dysfunction and re-entrant arrhythmia.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_1.html#pathophysiology-ventricular-hypertrophy-myocyte-disarray-and-fibrosis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:1:model:kb/disorders/Hypertrophic_Cardiomyopathy_1.yaml:MYH7 G256E gene-edited hiPSC-cardiomyocyte multiscale platform","source_id":"model:kb/disorders/Hypertrophic_Cardiomyopathy_1.yaml:MYH7 G256E gene-edited hiPSC-cardiomyocyte multiscale platform","target_id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Sarcomere%20Hypercontractility%20with%20Impaired%20Relaxation","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[1]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"Greater and faster tension development was reproduced in myofibrils, in single cells and in engineered heart tissue from the same edited line.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AHypertrophic_Cardiomyopathy_1:2:0","source_id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Increased%20Motor%20Force%20and%20Energetic%20Cost","target_id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Sarcomere%20Hypercontractility%20with%20Impaired%20Relaxation","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Raised ensemble force and disturbed cross-bridge kinetics translate into cellular hypercontractility with impaired diastolic relaxation.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3AHypertrophic_Cardiomyopathy_1:3:1","source_id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Sarcomere%20Hypercontractility%20with%20Impaired%20Relaxation","target_id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Cardiomyocyte-to-Fibroblast%20EGFR%20Paracrine%20Signaling","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[3].downstream[1]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"The mutant cardiomyocyte does not remodel the interstitium by mechanical load alone: it secretes soluble factors that act on the neighbouring fibroblast population. What couples the contractile state to that secretion is not established. 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hiPSC-CMs impaired relaxation or increased force, mimicking early features observed in human HCM.","explanation":"States that the model reproduces the early cellular features this node describes."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Hypertrophic_Cardiomyopathy_1","model_node_id":"model:kb/disorders/Hypertrophic_Cardiomyopathy_1.yaml:MYH7 R403Q and TNNT2 R92Q hiPSC-cardiomyocyte engineered heart tissue","focus_node_id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Sarcomere%20Hypercontractility%20with%20Impaired%20Relaxation","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_1.html#pathograph","nodes":[{"id":"model:kb/disorders/Hypertrophic_Cardiomyopathy_1.yaml:MYH7 R403Q and TNNT2 R92Q hiPSC-cardiomyocyte engineered heart tissue","kind":"experimental_model","kind_label":"NAM model","label":"MYH7 R403Q and TNNT2 R92Q hiPSC-cardiomyocyte 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Relaxation improved with SGLT2 inhibitors, and the effect grew with culture duration as the tissue matured.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_1.html#experimental-model-myh7-r403q-and-tnnt2-r92q-hipsc-cardiomyocyte-engineered-heart-tissue","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Sarcomere%20Hypercontractility%20with%20Impaired%20Relaxation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Sarcomere Hypercontractility with Impaired Relaxation","description":"At the cell level the molecular changes converge on hypercontractility: CRISPR-edited human iPSC-derived cardiomyocytes carrying an MYH7 HCM mutation generate significantly greater contractile force than isogenic controls. Because the same lesion disturbs cross-bridge relaxation kinetics, systolic hypercontraction is accompanied by impaired diastolic relaxation. This hypercontractile, poorly relaxing cell state — a key pathophysiological abnormality of HCM and the determinant of dynamic outflow obstruction — is the cellular phenotype the cardiac myosin inhibitors were designed to normalize.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_1.html#pathophysiology-sarcomere-hypercontractility-with-impaired-relaxation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Cardiomyocyte-to-Fibroblast%20EGFR%20Paracrine%20Signaling","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Cardiomyocyte-to-Fibroblast EGFR Paracrine Signaling","description":"Interstitial fibrosis in CMH1 is not solely a passive response to wall stress. 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The same microtissue system shows that the tissue-level consequence is hypocontractility even while the individual mutant cardiomyocytes are hypercontractile, which is how a cell-autonomous gain of contractile function ends up producing a stiff, poorly contracting ventricle.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_1.html#pathophysiology-cardiomyocyte-to-fibroblast-egfr-paracrine-signaling","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Cell-to-Cell%20Contractile%20Imbalance","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Cell-to-Cell Contractile Imbalance","description":"A mechanism specific to the missense/poison-peptide biology of MYH7 disease. Because the mutant and wild-type MYH7 alleles are transcribed in a random, burst-like fashion and independently of one another, the fraction of mutant beta-myosin varies markedly from cardiomyocyte to cardiomyocyte within a single patient's myocardium. This produces much greater cell-to-cell variability of contractile function than in control hearts. The resulting mechanical mismatch between adjacent, differently loaded myocytes is proposed to drive the myofiber disarray and interstitial fibrosis that are hallmarks of HCM, providing a route from the molecular lesion to the tissue phenotype that does not depend on the average level of hypercontractility alone.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_1.html#pathophysiology-cell-to-cell-contractile-imbalance","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Increased%20Motor%20Force%20and%20Energetic%20Cost","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Increased Motor Force and Energetic Cost","description":"Beyond releasing sequestered heads, individual MYH7 missense alleles alter the mechanochemistry of the motor stroke itself. Single-molecule and myofibril studies show mutation-specific changes — increased intrinsic force per cross-bridge, and faster cross-bridge detachment kinetics — that together raise the force generated by the ensemble of motors and increase the ATP consumed per unit tension (tension cost). The energetic penalty, measured directly in human myocardium carrying R403Q, is a distinctive feature of the beta-myosin motor lesion and links the molecular defect to the myocardial energy deficit seen in HCM.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_1.html#pathophysiology-increased-motor-force-and-energetic-cost","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Ventricular%20Hypertrophy%2C%20Myocyte%20Disarray%20and%20Fibrosis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Ventricular Hypertrophy, Myocyte Disarray and Fibrosis","description":"Chronic hypercontractility with raised energetic cost, amplified by cell-to-cell contractile imbalance, drives the structural remodeling that defines the clinical phenotype: cardiomyocyte hypertrophy — typically asymmetric and septal-predominant — together with myofiber disarray and interstitial and replacement fibrosis. Pro-hypertrophic growth signalling contributes: in an MYH7-mutant human iPSC-cardiomyocyte model, cellular hypertrophy was prevented by inhibition of ERK or Akt, implicating those pathways downstream of the mechanical stimulus. Fibrosis provides the substrate for both diastolic dysfunction and re-entrant arrhythmia.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_1.html#pathophysiology-ventricular-hypertrophy-myocyte-disarray-and-fibrosis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Hypertrophic_Cardiomyopathy_1.yaml:MYH7 R403Q and TNNT2 R92Q hiPSC-cardiomyocyte engineered heart tissue","source_id":"model:kb/disorders/Hypertrophic_Cardiomyopathy_1.yaml:MYH7 R403Q and TNNT2 R92Q hiPSC-cardiomyocyte engineered heart tissue","target_id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Sarcomere%20Hypercontractility%20with%20Impaired%20Relaxation","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"Reproduces the impaired-relaxation and increased-force halves of the node in a human system carrying the archetypal CMH1 allele.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AHypertrophic_Cardiomyopathy_1:2:0","source_id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Increased%20Motor%20Force%20and%20Energetic%20Cost","target_id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Sarcomere%20Hypercontractility%20with%20Impaired%20Relaxation","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Raised ensemble force and disturbed cross-bridge kinetics translate into cellular hypercontractility with impaired diastolic relaxation.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3AHypertrophic_Cardiomyopathy_1:3:1","source_id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Sarcomere%20Hypercontractility%20with%20Impaired%20Relaxation","target_id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Cardiomyocyte-to-Fibroblast%20EGFR%20Paracrine%20Signaling","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[3].downstream[1]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"The mutant cardiomyocyte does not remodel the interstitium by mechanical load alone: it secretes soluble factors that act on the neighbouring fibroblast population. What couples the contractile state to that secretion is not established. The source proposes a broader stress response, with mechanical signalling from the intrinsic hypercontractility as one candidate, and states that further work is needed to identify the ligands and receptors involved — so the edge is curated with unknown intermediates rather than as a direct link.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AHypertrophic_Cardiomyopathy_1:3:0","source_id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Sarcomere%20Hypercontractility%20with%20Impaired%20Relaxation","target_id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Cell-to-Cell%20Contractile%20Imbalance","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[3].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Because mutant and wild-type 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It is the tissue substrate that links the mechanism modeled in this entry's pathophysiology to the arrhythmic risk modeled in its phenotypes.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_1.html#phenotype-myocardial-fibrosis","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Sarcomere%20Hypercontractility%20with%20Impaired%20Relaxation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Sarcomere Hypercontractility with Impaired Relaxation","description":"At the cell level the molecular changes converge on hypercontractility: CRISPR-edited human iPSC-derived cardiomyocytes carrying an MYH7 HCM mutation generate significantly greater contractile force than isogenic controls. 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This hypercontractile, poorly relaxing cell state — a key pathophysiological abnormality of HCM and the determinant of dynamic outflow obstruction — is the cellular phenotype the cardiac myosin inhibitors were designed to normalize.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_1.html#pathophysiology-sarcomere-hypercontractility-with-impaired-relaxation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Ventricular%20Hypertrophy%2C%20Myocyte%20Disarray%20and%20Fibrosis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Ventricular Hypertrophy, Myocyte Disarray and Fibrosis","description":"Chronic hypercontractility with raised energetic cost, amplified by cell-to-cell contractile imbalance, drives the structural remodeling that defines the clinical phenotype: cardiomyocyte hypertrophy — typically asymmetric and septal-predominant — together with myofiber disarray and interstitial and replacement fibrosis. 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Fibrosis provides the substrate for both diastolic dysfunction and re-entrant arrhythmia.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_1.html#pathophysiology-ventricular-hypertrophy-myocyte-disarray-and-fibrosis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Hypertrophic_Cardiomyopathy_1.yaml:MYH7 R403Q hiPSC-cardiomyocyte cardiac microtissue with wild-type fibroblasts","source_id":"model:kb/disorders/Hypertrophic_Cardiomyopathy_1.yaml:MYH7 R403Q hiPSC-cardiomyocyte cardiac microtissue with wild-type fibroblasts","target_id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Cardiomyocyte-to-Fibroblast%20EGFR%20Paracrine%20Signaling","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"The model was built to interrogate this node and demonstrates each of its claims — paracrine transfer, fibroblast proliferation dependence, and EGFR as the transducing receptor.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AHypertrophic_Cardiomyopathy_1:4:1","source_id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Cardiomyocyte-to-Fibroblast%20EGFR%20Paracrine%20Signaling","target_id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:phenotype:Myocardial%20Fibrosis","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[4].downstream[1]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"The same collagen deposition presenting as the clinically measurable fibrosis burden, imaged as late gadolinium enhancement.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3AHypertrophic_Cardiomyopathy_1:4:0","source_id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Cardiomyocyte-to-Fibroblast%20EGFR%20Paracrine%20Signaling","target_id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Ventricular%20Hypertrophy%2C%20Myocyte%20Disarray%20and%20Fibrosis","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[4].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Fibroblast activation and excess collagen deposition are the cellular mechanism of the interstitial fibrosis component of the tissue-level remodeling node.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3AHypertrophic_Cardiomyopathy_1:3:1","source_id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Sarcomere%20Hypercontractility%20with%20Impaired%20Relaxation","target_id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Cardiomyocyte-to-Fibroblast%20EGFR%20Paracrine%20Signaling","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[3].downstream[1]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"The mutant cardiomyocyte does not remodel the interstitium by mechanical load alone: it secretes soluble factors that act on the neighbouring fibroblast population. What couples the contractile state to that secretion is not established. The source proposes a broader stress response, with mechanical signalling from the intrinsic hypercontractility as one candidate, and states that further work is needed to identify the ligands and receptors involved — so the edge is curated with unknown intermediates rather than as a direct link.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1}]}},{"target":"Ventricular Hypertrophy, Myocyte Disarray and Fibrosis","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_1.html#pathophysiology-ventricular-hypertrophy-myocyte-disarray-and-fibrosis","relationship":"PARTIALLY_RECAPITULATES","relationship_label":"Partially Recapitulates","fidelity":"LOW","fidelity_label":"Low","description":"Reproduces the interstitial-fibrosis and stiffening component of the remodeling node.","limitations":"It reproduces only one of the node's three components. There is no ventricular hypertrophy and no myofibre disarray in a microtissue, and the model observes cellular-scale readouts while the node is a tissue-scale claim, so the tissue-level inference is an upward extrapolation.","biological_scale":"TISSUE","anatomy":[{"id":"UBERON:0002094","label":"interventricular septum","display_label":"Interventricular septum","url":"http://purl.obolibrary.org/obo/UBERON_0002094"},{"id":"UBERON:0002084","label":"heart left ventricle","display_label":"Left ventricle","url":"http://purl.obolibrary.org/obo/UBERON_0002084"}],"cell_types":[{"id":"CL:0000746","label":"cardiac muscle cell","display_label":"Cardiomyocyte","url":"http://purl.obolibrary.org/obo/CL_0000746"},{"id":"CL:0002548","label":"fibroblast of cardiac tissue","display_label":"Cardiac Fibroblast","url":"http://purl.obolibrary.org/obo/CL_0002548"}],"biological_processes":[{"id":"GO:0014898","label":"cardiac muscle hypertrophy in response to stress","display_label":"Cardiac Muscle Hypertrophy in Response to Stress","url":"http://purl.obolibrary.org/obo/GO_0014898"},{"id":"GO:0030198","label":"extracellular matrix organization","display_label":"Extracellular Matrix Organization","url":"http://purl.obolibrary.org/obo/GO_0030198"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[],"evidence":[],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Hypertrophic_Cardiomyopathy_1","model_node_id":"model:kb/disorders/Hypertrophic_Cardiomyopathy_1.yaml:MYH7 R403Q hiPSC-cardiomyocyte cardiac microtissue with wild-type fibroblasts","focus_node_id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Ventricular%20Hypertrophy%2C%20Myocyte%20Disarray%20and%20Fibrosis","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_1.html#pathograph","nodes":[{"id":"model:kb/disorders/Hypertrophic_Cardiomyopathy_1.yaml:MYH7 R403Q hiPSC-cardiomyocyte cardiac microtissue with wild-type fibroblasts","kind":"experimental_model","kind_label":"NAM model","label":"MYH7 R403Q hiPSC-cardiomyocyte cardiac microtissue with wild-type fibroblasts","description":"Engineered three-dimensional cardiac microtissues built from isogenic MYH7 R403Q heterozygous hiPSC-derived cardiomyocytes together with wild-type ventricular cardiac fibroblasts. The co-culture is the point: a cardiomyocyte-only model cannot show the cardiomyocyte-to-fibroblast cross-talk that produces the fibrotic component of the disease, and this system reproduces collagen deposition, tissue stiffening and the EGFR dependence of stromal activation.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_1.html#experimental-model-myh7-r403q-hipsc-cardiomyocyte-cardiac-microtissue-with-wild-type-fibroblasts","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Ventricular%20Hypertrophy%2C%20Myocyte%20Disarray%20and%20Fibrosis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Ventricular Hypertrophy, Myocyte Disarray and Fibrosis","description":"Chronic hypercontractility with raised energetic cost, amplified by cell-to-cell contractile imbalance, drives the structural remodeling that defines the clinical phenotype: cardiomyocyte hypertrophy — typically asymmetric and septal-predominant — together with myofiber disarray and interstitial and replacement fibrosis. Pro-hypertrophic growth signalling contributes: in an MYH7-mutant human iPSC-cardiomyocyte model, cellular hypertrophy was prevented by inhibition of ERK or Akt, implicating those pathways downstream of the mechanical stimulus. Fibrosis provides the substrate for both diastolic dysfunction and re-entrant arrhythmia.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_1.html#pathophysiology-ventricular-hypertrophy-myocyte-disarray-and-fibrosis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Cardiomyocyte-to-Fibroblast%20EGFR%20Paracrine%20Signaling","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Cardiomyocyte-to-Fibroblast EGFR Paracrine Signaling","description":"Interstitial fibrosis in CMH1 is not solely a passive response to wall stress. In engineered cardiac microtissues built from MYH7 R403Q hiPSC-derived cardiomyocytes co-cultured with wild-type ventricular cardiac fibroblasts, the mutant cardiomyocytes release paracrine factors that drive fibroblast proliferation and collagen deposition. Collagen I content rose 40% over isogenic wild-type microtissues and the tissue stiffened, and the effect depended on fibroblast proliferation rather than on cardiomyocyte matrix output. Epidermal growth factor alone was sufficient to stimulate the stromal cells, and inhibiting EGFR tyrosine kinase with erlotinib attenuated the activation — identifying EGFR signalling as the transducing arm and, in principle, a druggable one. The same microtissue system shows that the tissue-level consequence is hypocontractility even while the individual mutant cardiomyocytes are hypercontractile, which is how a cell-autonomous gain of contractile function ends up producing a stiff, poorly contracting ventricle.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_1.html#pathophysiology-cardiomyocyte-to-fibroblast-egfr-paracrine-signaling","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Cell-to-Cell%20Contractile%20Imbalance","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Cell-to-Cell Contractile Imbalance","description":"A mechanism specific to the missense/poison-peptide biology of MYH7 disease. 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The resulting mechanical mismatch between adjacent, differently loaded myocytes is proposed to drive the myofiber disarray and interstitial fibrosis that are hallmarks of HCM, providing a route from the molecular lesion to the tissue phenotype that does not depend on the average level of hypercontractility alone.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_1.html#pathophysiology-cell-to-cell-contractile-imbalance","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Diastolic%20Dysfunction%2C%20Outflow%20Obstruction%2C%20Heart%20Failure%20and%20Arrhythmic%20Risk","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Diastolic Dysfunction, Outflow Obstruction, Heart Failure and Arrhythmic Risk","description":"The hypertrophied, disarrayed and fibrotic ventricle produces the clinical endpoints of CMH1. Hypercontractility with septal hypertrophy generates dynamic left ventricular outflow tract obstruction in a subset of patients; the stiff, poorly relaxing ventricle causes diastolic dysfunction; and the fibrotic, electrically heterogeneous substrate carries a risk of malignant ventricular arrhythmia and sudden cardiac death that is clinically important for MYH7 variants. Sarcomere-positive disease, of which MYH7 is a leading cause, presents younger and with a stronger family history of sudden death than sarcomere-negative HCM.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_1.html#pathophysiology-diastolic-dysfunction-outflow-obstruction-heart-failure-and-arrhythmic-risk","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_1:pathophysiology:Sarcomere%20Hypercontractility%20with%20Impaired%20Relaxation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Sarcomere Hypercontractility with Impaired Relaxation","description":"At the cell level the molecular changes converge on hypercontractility: CRISPR-edited human iPSC-derived cardiomyocytes carrying an MYH7 HCM mutation generate significantly greater contractile force than isogenic controls. 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Its value is that it shows hypertrophy, disarray and calcium abnormality arising from the human genotype alone, in cells that have never experienced a pressure load — which separates the cell-autonomous consequences of the allele from the consequences of living in a hypertrophied heart.","notes":null,"context_id":"disorder:Hypertrophic_Cardiomyopathy_10","context_kind":"Disorder","disease_name":"Hypertrophic Cardiomyopathy 10","disease_synonyms":["CMH10","MYL2 hypertrophic cardiomyopathy","ventricular regulatory myosin light chain hypertrophic cardiomyopathy","cardiomyopathy, familial hypertrophic, 10","hypertrophic cardiomyopathy caused by mutation in MYL2"],"disease_term":{"id":"MONDO:0012112","label":"hypertrophic cardiomyopathy 10","display_label":"hypertrophic cardiomyopathy 10","url":"http://purl.obolibrary.org/obo/MONDO_0012112"},"experimental_model_type":"IPSC_DERIVED_MODEL","experimental_model_type_label":"iPSC-derived 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The second is that the authors chose NDUFA11 precisely because of the cryo-EM structures this entry also cites - so the biochemical and structural lines of evidence are one argument rather than two coincidences.","notes":null,"context_id":"disorder:Mitochondrial_Complex_I_Deficiency_Nuclear_Type_14","context_kind":"Disorder","disease_name":"Mitochondrial Complex I Deficiency, Nuclear Type 14","disease_synonyms":["MC1DN14","NDUFA11 deficiency","NDUFA11-related mitochondrial complex I deficiency","B14.7 deficiency"],"disease_term":{"id":"MONDO:0032619","label":"mitochondrial complex I deficiency, nuclear type 14","display_label":"Mitochondrial complex I deficiency, nuclear type 14","url":"http://purl.obolibrary.org/obo/MONDO_0032619"},"experimental_model_type":"CELL_LINE","experimental_model_type_label":"Cell line","namo_type":"namo:CellLineModel","declared_namo_class_name":null,"namo_class_name":"CellLineModel","namo_class_label":"Cell Line Model","namo_description":"A model system based on immortalized cell lines that can be maintained in culture indefinitely. Examples: HepG2, A549, Caco-2, etc.","namo_docs_url":"https://monarch-initiative.github.io/namo/elements/CellLineModel/","namo_ontology_url":"https://w3id.org/monarch-initiative/namo/CellLineModel","namo_mapping_basis":"Safe mapping from DisMech category","namo_class_in_schema":true,"namo_schema_status":"Defined in NAMO schema used for this build","modality":"Cellular system","organism":{"id":"NCBITaxon:10116","label":"Rattus norvegicus","display_label":"rat","url":"http://purl.obolibrary.org/obo/NCBITaxon_10116"},"organism_label":"Rattus norvegicus","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":"H9c2 embryonic rat cardioblast line (ATCC)","source_category":"Immortalized / cell line","culture_system":"Two-dimensional monolayer culture; siRNA transfection","publication":"PMID:30531981","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/30531981","mechanisms":[{"target":"Impaired Supercomplex Assembly","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_14.html#pathophysiology-impaired-supercomplex-assembly","relationship":"RECAPITULATES","relationship_label":"Recapitulates","fidelity":"MODERATE","fidelity_label":"Moderate","description":"Loss of NDUFA11 disintegrates the respirasome and collapses the activity of the partner complexes, which is this node's claim measured directly rather than inferred from where the subunit sits in a structure.","limitations":"An immortalised rat cardioblast line under acute siRNA knockdown, not human patient tissue carrying the chronic splice-site allele, so it cannot show that the same thing happens in a person or that a lifetime of it is what makes patients ill. More substantively, the model and the disease disagree on one point that this entry records rather than smooths over: NDUFA11 silencing cut complex III activity by 63-72 percent and complex IV by about 71 percent alongside complex I, whereas the patients' biochemistry is reported as an *isolated* complex I deficiency. Either the patients' allele is milder than an siRNA knockdown, or a supercomplex phenotype is present in patients and has not been looked for. Both are testable and neither has been tested.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0097250","label":"mitochondrial respirasome assembly","display_label":"respirasome assembly","url":"http://purl.obolibrary.org/obo/GO_0097250"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Respirasome level","description":null,"target":"Impaired Supercomplex Assembly","direction":"DECREASED","interpretation":"Respirasome abundance falls with NDUFA11 loss, reproducibly across two independent siRNAs, though the size of the effect differs between them (13 percent versus 30 percent) - so the direction is solid and the magnitude is knockdown-depth dependent.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:30531981","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30531981","reference_title":"Elucidating the contribution of ETC complexes I and II to the respirasome formation in cardiac mitochondria.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Analysis of SCs revealed a 13% and 30% (P < 0.01 vs control for both) decrease in respirasome levels in NDUFA11 siRNA-I and siRNA-II treated cells, respectively","explanation":"The quantified respirasome loss, with both siRNAs and their p-values. Quoted with both figures rather than the larger one, because the two-fold spread between them is part of what the measurement says."}],"notes":null},{"name":"Complex III and complex IV enzymatic activity","description":null,"target":"Impaired Supercomplex Assembly","direction":"DECREASED","interpretation":"The functional signature of a supercomplex defect rather than an isolated complex I lesion: losing a complex I subunit takes down the activity of the complexes it is docked against.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:30531981","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30531981","reference_title":"Elucidating the contribution of ETC complexes I and II to the respirasome formation in cardiac mitochondria.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"NDUFA11 silencing induced a 72% (P < 0.01) and 63% (P < 0.05) decrease of complex III activity in cells treated with by siRNA-I and siRNA-II, respectively.","explanation":"Quantifies the complex III collapse. This is also the measurement behind the limitation recorded on this link - it is what the patients' isolated complex I deficiency does not obviously match."},{"reference":"PMID:30531981","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30531981","reference_title":"Elucidating the contribution of ETC complexes I and II to the respirasome formation in cardiac mitochondria.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Likewise, NDUFA11 knockdown markedly reduced the complex IV activity which was 71% and 72% (P < 0.05 for both) lower in cells treated with siRNA-I and siRNA-II, respectively, compared to cells treated with negative control siRNA.","explanation":"The same effect on complex IV, and unlike the respirasome readout the two siRNAs agree closely here."}],"notes":null},{"name":"Respirasome level after complex II subunit knockdown","description":null,"target":"Impaired Supercomplex Assembly","direction":"UNCHANGED","interpretation":"The specificity control, and a real negative result: silencing the complex II subunit SDHC reduced complex II activity without disintegrating the respirasome, so the NDUFA11 effect is attributable to NDUFA11 rather than to perturbing the inner membrane in general.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:30531981","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30531981","reference_title":"Elucidating the contribution of ETC complexes I and II to the respirasome formation in cardiac mitochondria.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Silencing of SDHC reduced enzymatic activity of complex II that, in contrast to isolated cardiac mitochondria, was not accompanied with respirasome disintegration in H9c2 cell.","explanation":"The control arm and its UNCHANGED result, quoted in the authors' own careful form - they note the contrast with isolated cardiac mitochondria rather than claiming SDHC is irrelevant everywhere. A negative control is what turns the NDUFA11 result from an observation into an attribution."}],"notes":null}],"evidence":[{"reference":"PMID:30531981","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30531981","reference_title":"Elucidating the contribution of ETC complexes I and II to the respirasome formation in cardiac mitochondria.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Our results demonstrate that NDUFA11 is involved in the respirasome assembly whereas SDHC is not a part of the respirasome.","explanation":"Establishes that this model is informative for the supercomplex node: the authors' stated conclusion is the node's claim, and it is stated against a control rather than alone."},{"reference":"PMID:30531981","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30531981","reference_title":"Elucidating the contribution of ETC complexes I and II to the respirasome formation in cardiac mitochondria.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Analysis of SCs revealed a 13% and 30% (P < 0.01 vs control for both) decrease in respirasome levels in NDUFA11 siRNA-I and siRNA-II treated cells, respectively","explanation":"The quantified respirasome loss, with both siRNAs and their p-values. Quoted with both figures rather than the larger one, because the two-fold spread between them is part of what the measurement says."},{"reference":"PMID:30531981","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30531981","reference_title":"Elucidating the contribution of ETC complexes I and II to the respirasome formation in cardiac mitochondria.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"NDUFA11 silencing induced a 72% (P < 0.01) and 63% (P < 0.05) decrease of complex III activity in cells treated with by siRNA-I and siRNA-II, respectively.","explanation":"Quantifies the complex III collapse. This is also the measurement behind the limitation recorded on this link - it is what the patients' isolated complex I deficiency does not obviously match."},{"reference":"PMID:30531981","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30531981","reference_title":"Elucidating the contribution of ETC complexes I and II to the respirasome formation in cardiac mitochondria.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Likewise, NDUFA11 knockdown markedly reduced the complex IV activity which was 71% and 72% (P < 0.05 for both) lower in cells treated with siRNA-I and siRNA-II, respectively, compared to cells treated with negative control siRNA.","explanation":"The same effect on complex IV, and unlike the respirasome readout the two siRNAs agree closely here."},{"reference":"PMID:30531981","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30531981","reference_title":"Elucidating the contribution of ETC complexes I and II to the respirasome formation in cardiac mitochondria.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Silencing of SDHC reduced enzymatic activity of complex II that, in contrast to isolated cardiac mitochondria, was not accompanied with respirasome disintegration in H9c2 cell.","explanation":"The control arm and its UNCHANGED result, quoted in the authors' own careful form - they note the contrast with isolated cardiac mitochondria rather than claiming SDHC is irrelevant everywhere. A negative control is what turns the NDUFA11 result from an observation into an attribution."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Mitochondrial_Complex_I_Deficiency_Nuclear_Type_14","model_node_id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_14.yaml:NDUFA11 siRNA knockdown in H9c2 cardioblasts","focus_node_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_14:pathophysiology:Impaired%20Supercomplex%20Assembly","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_14.html#pathograph","nodes":[{"id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_14.yaml:NDUFA11 siRNA knockdown in H9c2 cardioblasts","kind":"experimental_model","kind_label":"NAM model","label":"NDUFA11 siRNA knockdown in H9c2 cardioblasts","description":"The only mammalian system in which NDUFA11 itself has been removed and the consequences measured, and therefore the most load-bearing piece of non-patient evidence in this entry. NDUFA11 was silenced with two independent siRNAs in H9c2 embryonic rat cardioblasts, and respirasome levels, individual complex activities, ATP, membrane potential and mitochondrial ROS were read out against a negative-control siRNA.\nTwo features make it more than a single-gene knockdown. The first is the comparison arm: silencing SDHC, the membrane-anchored subunit of complex II, did not disintegrate the respirasome, so respirasome loss is not the generic consequence of removing any inner-membrane respiratory subunit. The second is that the authors chose NDUFA11 precisely because of the cryo-EM structures this entry also cites - so the biochemical and structural lines of evidence are one argument rather than two coincidences.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_14.html#experimental-model-ndufa11-sirna-knockdown-in-h9c2-cardioblasts","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_14:pathophysiology:Impaired%20Supercomplex%20Assembly","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Supercomplex Assembly","description":"The node that is specific to this subunit rather than generic to complex I deficiency. Two independent cryo-EM structures of the mammalian respirasome place NDUFA11 at the contact between complex I and complex III, and name it among the handful of complex I subunits that hold the supercomplex together. If that interface is what a patient loses, then MC1DN14 is not only a complex I deficiency but a supercomplex assembly defect.\nThat is not merely inferred from the structures. Silencing NDUFA11 with two independent siRNAs in rat H9c2 cardioblasts disintegrates the respirasome and drops complex III and complex IV activity by 63-72 percent alongside complex I - and silencing a complex II subunit in the same system does not, so the effect is attributable to NDUFA11 rather than to perturbing the inner membrane. The C. elegans knockdown reports the same combination independently. So the mechanism itself is demonstrated, in the right gene, with a functional consequence and a negative control attached.\nIt is graded PROVISIONAL rather than established because the step that remains untaken is the one to a patient. Nobody has run blue native gel electrophoresis on tissue from an NDUFA11-deficient patient and asked whether the respirasome is present, which is the experiment this node is waiting on and the subject of an open discussion below. Note also that the knockdown result cuts both ways for the entry's own logic: reduced complex III and IV activity alongside complex I is what a supercomplex defect predicts, yet the patients' biochemistry is described as an isolated complex I deficiency.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_14.html#pathophysiology-impaired-supercomplex-assembly","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_14:pathophysiology:Isolated%20Complex%20I%20Deficiency","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Isolated Complex I Deficiency","description":"The measured endpoint of the molecular lesion and the biochemical phenotype that defines the entity's name. Isolated means complex I activity is reduced while the other respiratory chain complexes are not, which is what makes a complex I subunit gene the place to look and is the biochemical entry point to the diagnosis.\nTagged MOLECULAR rather than CELLULAR on the schema's own terms: the substrate is an enzyme complex and the claim is that it is deficient.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_14.html#pathophysiology-isolated-complex-i-deficiency","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_14:pathophysiology:Loss%20of%20the%20NDUFA11%20First%20Transmembrane%20Helix","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Loss of the NDUFA11 First Transmembrane Helix","description":"The proposed protein-level consequence of the splice-site allele: the transcript loses the sequence encoding the first membrane-spanning helix, so the subunit can no longer be anchored in the inner membrane where it belongs.\nGraded PROVISIONAL deliberately. The source states this as a prediction, and the entry says the same. No western blot, no complexome profile, and no transcript analysis of a patient sample is reported in the material that can be verified here, so what is on record is a sequence-based inference about the mutant product and not a measurement of it.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_14.html#pathophysiology-loss-of-the-ndufa11-first-transmembrane-helix","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"}],"edges":[{"id":"model-link:0:model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_14.yaml:NDUFA11 siRNA knockdown in H9c2 cardioblasts","source_id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_14.yaml:NDUFA11 siRNA knockdown in H9c2 cardioblasts","target_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_14:pathophysiology:Impaired%20Supercomplex%20Assembly","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"Loss of NDUFA11 disintegrates the respirasome and collapses the activity of the partner complexes, which is this node's claim measured directly rather than inferred from where the subunit sits in a structure.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_14:3:0","source_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_14:pathophysiology:Impaired%20Supercomplex%20Assembly","target_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_14:pathophysiology:Isolated%20Complex%20I%20Deficiency","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[3].downstream[0]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_14:1:1","source_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_14:pathophysiology:Loss%20of%20the%20NDUFA11%20First%20Transmembrane%20Helix","target_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_14:pathophysiology:Impaired%20Supercomplex%20Assembly","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[1]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0}]}},{"target":"Impaired Mitochondrial NADH Reoxidation and ATP Synthesis","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_14.html#pathophysiology-impaired-mitochondrial-nadh-reoxidation-and-atp-synthesis","relationship":"RECAPITULATES","relationship_label":"Recapitulates","fidelity":"MODERATE","fidelity_label":"Moderate","description":"NDUFA11 knockdown halves cellular ATP, depolarises the inner membrane and raises mitochondrial ROS - the bioenergetic consequences this node asserts, measured on loss of the gene this entry is about.","limitations":"An acutely silenced rat cell line, so it does not speak to the chronic, whole-organism energy deficit that reaches a patient's heart and brain, and cardioblasts are proliferating cells whose energetic demands differ from those of post-mitotic myocardium.\nThe ROS half of this link is not specific to NDUFA11: knocking down the complex II subunit SDHC raised mitochondrial ROS as well, and by a larger margin (114 and 82 percent, against 62 and 30 percent for NDUFA11) even though the paper's own prose characterises the two as similar effects. So raised mitochondrial ROS reads here as a general consequence of losing respiratory capacity rather than as a signature of losing this subunit. The membrane-potential half is a different matter - SDHC knockdown did not affect membrane potential at all - and that specificity is recorded on the readout below.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0006120","label":"mitochondrial electron transport, NADH to ubiquinone","display_label":"mitochondrial electron transport, NADH to ubiquinone","url":"http://purl.obolibrary.org/obo/GO_0006120"},{"id":"GO:0072593","label":"reactive oxygen species metabolic process","display_label":"mitochondrial reactive oxygen species production","url":"http://purl.obolibrary.org/obo/GO_0072593"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Cellular ATP level","description":null,"target":"Impaired Mitochondrial NADH Reoxidation and ATP Synthesis","direction":"DECREASED","interpretation":"ATP falls to roughly half of control, identically for both siRNAs, which is the bioenergetic endpoint of the whole chain in this entry.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:30531981","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30531981","reference_title":"Elucidating the contribution of ETC complexes I and II to the respirasome formation in cardiac mitochondria.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Silencing of NDUFA11 by siRNA-I and siRNA-II was equally effective and decreased the ATP level to 48% (P < 0.01 for both)","explanation":"The quantified ATP deficit, with the agreement between the two independent siRNAs that makes it attributable to loss of NDUFA11."}],"notes":null},{"name":"Mitochondrial membrane potential","description":null,"target":"Impaired Mitochondrial NADH Reoxidation and ATP Synthesis","direction":"DECREASED","interpretation":"The proton-motive force behind ATP synthesis is itself reduced, which is the mechanistic link between losing a proton-pumping complex and losing ATP rather than merely a second symptom of it. Unlike the ROS readout, this one is specific to NDUFA11: silencing the complex II subunit SDHC left membrane potential untouched, which is what one would predict if the depolarisation follows from losing a proton pump rather than from a general loss of respiratory capacity.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:30531981","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30531981","reference_title":"Elucidating the contribution of ETC complexes I and II to the respirasome formation in cardiac mitochondria.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Diminished ATP synthesis in NDUFA11 silenced cells was associated with the loss of ΔΨm, which was 47% (P < 0.01) and 14% (P < 0.05) lower for siRNA-1 and siRNA-2, respectively, compared to control cells","explanation":"Connects the ATP fall to membrane depolarisation. The two siRNAs differ widely here (47 versus 14 percent), so the direction is supported and the magnitude is not well constrained."},{"reference":"PMID:30531981","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30531981","reference_title":"Elucidating the contribution of ETC complexes I and II to the respirasome formation in cardiac mitochondria.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"In contrast to NDUFA11, SDHC silencing by both siRNAs did not affect the ΔΨm","explanation":"The specificity control for this readout, and the reason the membrane-potential result is treated differently from the ROS result on the same link: losing a complex II subunit did not depolarise the membrane, so the depolarisation on NDUFA11 loss is attributable to losing a proton-pumping complex rather than to reduced respiration in general. INDIRECT for the same non-human cell line reason as every other item from this paper."}],"notes":null},{"name":"Mitochondrial reactive oxygen species production","description":null,"target":"Impaired Mitochondrial NADH Reoxidation and ATP Synthesis","direction":"INCREASED","interpretation":"The oxidative-stress half of the node, and the observation that grounds the INCREASED reactive-oxygen-species process the conformed module node declares.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:30531981","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30531981","reference_title":"Elucidating the contribution of ETC complexes I and II to the respirasome formation in cardiac mitochondria.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Mitochondrial ROS levels were 62% and 30% higher (P < 0.01 for both) in the cells treated with NDUFA11 siRNA-1 and siRNA-2, respectively, in comparison with negative control siRNA-treated cells","explanation":"A measured rise in mitochondrial ROS, unlike the C. elegans study's statement, which reports only a potential for ROS production and is quoted elsewhere in this entry with that hedge intact."}],"notes":null}],"evidence":[{"reference":"PMID:30531981","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30531981","reference_title":"Elucidating the contribution of ETC complexes I and II to the respirasome formation in cardiac mitochondria.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Next, we evaluated the effects of NDUFA11 and SDHC silencing on ATP synthesis and ROS production in H9c2 cells.","explanation":"Establishes that the bioenergetic readouts for this node were taken in this model on NDUFA11 knockdown."},{"reference":"PMID:30531981","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30531981","reference_title":"Elucidating the contribution of ETC complexes I and II to the respirasome formation in cardiac mitochondria.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Silencing of NDUFA11 by siRNA-I and siRNA-II was equally effective and decreased the ATP level to 48% (P < 0.01 for both)","explanation":"The quantified ATP deficit, with the agreement between the two independent siRNAs that makes it attributable to loss of NDUFA11."},{"reference":"PMID:30531981","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30531981","reference_title":"Elucidating the contribution of ETC complexes I and II to the respirasome formation in cardiac mitochondria.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Diminished ATP synthesis in NDUFA11 silenced cells was associated with the loss of ΔΨm, which was 47% (P < 0.01) and 14% (P < 0.05) lower for siRNA-1 and siRNA-2, respectively, compared to control cells","explanation":"Connects the ATP fall to membrane depolarisation. The two siRNAs differ widely here (47 versus 14 percent), so the direction is supported and the magnitude is not well constrained."},{"reference":"PMID:30531981","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30531981","reference_title":"Elucidating the contribution of ETC complexes I and II to the respirasome formation in cardiac mitochondria.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"In contrast to NDUFA11, SDHC silencing by both siRNAs did not affect the ΔΨm","explanation":"The specificity control for this readout, and the reason the membrane-potential result is treated differently from the ROS result on the same link: losing a complex II subunit did not depolarise the membrane, so the depolarisation on NDUFA11 loss is attributable to losing a proton-pumping complex rather than to reduced respiration in general. INDIRECT for the same non-human cell line reason as every other item from this paper."},{"reference":"PMID:30531981","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30531981","reference_title":"Elucidating the contribution of ETC complexes I and II to the respirasome formation in cardiac mitochondria.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Mitochondrial ROS levels were 62% and 30% higher (P < 0.01 for both) in the cells treated with NDUFA11 siRNA-1 and siRNA-2, respectively, in comparison with negative control siRNA-treated cells","explanation":"A measured rise in mitochondrial ROS, unlike the C. elegans study's statement, which reports only a potential for ROS production and is quoted elsewhere in this entry with that hedge intact."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Mitochondrial_Complex_I_Deficiency_Nuclear_Type_14","model_node_id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_14.yaml:NDUFA11 siRNA knockdown in H9c2 cardioblasts","focus_node_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_14:pathophysiology:Impaired%20Mitochondrial%20NADH%20Reoxidation%20and%20ATP%20Synthesis","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_14.html#pathograph","nodes":[{"id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_14.yaml:NDUFA11 siRNA knockdown in H9c2 cardioblasts","kind":"experimental_model","kind_label":"NAM model","label":"NDUFA11 siRNA knockdown in H9c2 cardioblasts","description":"The only mammalian system in which NDUFA11 itself has been removed and the consequences measured, and therefore the most load-bearing piece of non-patient evidence in this entry. NDUFA11 was silenced with two independent siRNAs in H9c2 embryonic rat cardioblasts, and respirasome levels, individual complex activities, ATP, membrane potential and mitochondrial ROS were read out against a negative-control siRNA.\nTwo features make it more than a single-gene knockdown. The first is the comparison arm: silencing SDHC, the membrane-anchored subunit of complex II, did not disintegrate the respirasome, so respirasome loss is not the generic consequence of removing any inner-membrane respiratory subunit. The second is that the authors chose NDUFA11 precisely because of the cryo-EM structures this entry also cites - so the biochemical and structural lines of evidence are one argument rather than two coincidences.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_14.html#experimental-model-ndufa11-sirna-knockdown-in-h9c2-cardioblasts","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_14:pathophysiology:Impaired%20Mitochondrial%20NADH%20Reoxidation%20and%20ATP%20Synthesis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Mitochondrial NADH Reoxidation and ATP Synthesis","description":"Complex I is the entry point for NADH-derived electrons into the respiratory chain and one of its three proton pumps, so a complex I deficiency both blocks NADH reoxidation and removes part of the proton-motive force that drives ATP synthesis. The C. elegans knockdown adds a detail that a purely bioenergetic account would miss: the lost NADH dehydrogenase activity is partly compensated by increased complex II flux, which keeps the chain running but is a route to reactive oxygen species rather than a rescue.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_14.html#pathophysiology-impaired-mitochondrial-nadh-reoxidation-and-atp-synthesis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_14:pathophysiology:Aberrant%20Cristae%20Morphology","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Aberrant Cristae Morphology","description":"Complex I and its supercomplexes are structural as well as catalytic residents of the inner membrane, so losing them can change the shape of the membrane itself. Cryo-electron tomography of the C. elegans nduf-11 knockdown found widened cristae junctions and a widened intermembrane space alongside the enzymatic defect.\nThis is curated because it is a distinct, measurable consequence rather than a restatement of the enzyme deficiency, and because it predicts something checkable in human tissue. It is HYPOTHETICAL for the human disease: the observation exists only in the worm, and no ultrastructural study of an NDUFA11 patient has been reported.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_14.html#pathophysiology-aberrant-cristae-morphology","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"HYPOTHETICAL","mechanism_confidence_label":"Hypothetical"},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_14:pathophysiology:Cytosolic%20Redox%20Shift%20and%20Lactate%20Accumulation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Cytosolic Redox Shift and Lactate Accumulation","description":"With NADH reoxidation blocked at complex I, the cytosolic NADH/NAD+ ratio rises and pyruvate is reduced to lactate to regenerate NAD+, so lactate accumulates. This is the classical systemic read-out of a respiratory chain defect and it is what one pole of the reported MC1DN14 cohort presented with.\nNamed for the mechanism rather than for the finding, so that it is not a near-duplicate of the `Lactic Acidosis` phenotype it feeds. The node is the reason lactate rises; the phenotype is the measured clinical consequence.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_14.html#pathophysiology-cytosolic-redox-shift-and-lactate-accumulation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_14:pathophysiology:Energy%20Deficit%20in%20Heart%20and%20Brain","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Energy Deficit in Heart and Brain","description":"Why the heart and the brain rather than every tissue: both have high, largely inflexible oxidative demand and little capacity to make up an ATP shortfall glycolytically, so a fixed proportional loss of respiratory capacity reaches a symptomatic threshold there first. The reported presentation of encephalocardiomyopathy is consistent with that account.\nGraded PROVISIONAL because the tissue-selectivity argument is inference from general bioenergetics; no study has measured respiratory capacity in cardiac or neural tissue from an NDUFA11 patient, and no alternative explanation such as tissue-specific NDUFA11 expression has been excluded.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_14.html#pathophysiology-energy-deficit-in-heart-and-brain","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_14:pathophysiology:Isolated%20Complex%20I%20Deficiency","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Isolated Complex I Deficiency","description":"The measured endpoint of the molecular lesion and the biochemical phenotype that defines the entity's name. Isolated means complex I activity is reduced while the other respiratory chain complexes are not, which is what makes a complex I subunit gene the place to look and is the biochemical entry point to the diagnosis.\nTagged MOLECULAR rather than CELLULAR on the schema's own terms: the substrate is an enzyme complex and the claim is that it is deficient.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_14.html#pathophysiology-isolated-complex-i-deficiency","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"}],"edges":[{"id":"model-link:1:model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_14.yaml:NDUFA11 siRNA knockdown in H9c2 cardioblasts","source_id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_14.yaml:NDUFA11 siRNA knockdown in H9c2 cardioblasts","target_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_14:pathophysiology:Impaired%20Mitochondrial%20NADH%20Reoxidation%20and%20ATP%20Synthesis","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[1]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"NDUFA11 knockdown halves cellular ATP, depolarises the inner membrane and raises mitochondrial ROS - the bioenergetic consequences this node asserts, measured on loss of the gene this entry is about.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_14:4:0","source_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_14:pathophysiology:Aberrant%20Cristae%20Morphology","target_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_14:pathophysiology:Impaired%20Mitochondrial%20NADH%20Reoxidation%20and%20ATP%20Synthesis","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[4].downstream[0]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_14:6:0","source_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_14:pathophysiology:Impaired%20Mitochondrial%20NADH%20Reoxidation%20and%20ATP%20Synthesis","target_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_14:pathophysiology:Cytosolic%20Redox%20Shift%20and%20Lactate%20Accumulation","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[6].downstream[0]","label":"Directly 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causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_14:5:0","source_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_14:pathophysiology:Isolated%20Complex%20I%20Deficiency","target_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_14:pathophysiology:Impaired%20Mitochondrial%20NADH%20Reoxidation%20and%20ATP%20Synthesis","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[5].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0}]}}],"mechanism_names":["Impaired 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ubiquinone","reactive oxygen species metabolic process"],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":["Respirasome level","Complex III and complex IV enzymatic activity","Respirasome level after complex II subunit knockdown","Cellular ATP level","Mitochondrial membrane potential","Mitochondrial reactive oxygen species production"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:30531981","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30531981","reference_title":"Elucidating the contribution of ETC complexes I and II to the respirasome formation in cardiac mitochondria.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Our results demonstrate that NDUFA11 is involved in the respirasome assembly whereas SDHC is not a part of the respirasome.","explanation":"Establishes that this model is informative for the supercomplex node: the authors' stated conclusion is the node's claim, and it is stated against a control rather than alone."},{"reference":"PMID:30531981","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30531981","reference_title":"Elucidating the contribution of ETC complexes I and II to the respirasome formation in cardiac mitochondria.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Analysis of SCs revealed a 13% and 30% (P < 0.01 vs control for both) decrease in respirasome levels in NDUFA11 siRNA-I and siRNA-II treated cells, respectively","explanation":"The quantified respirasome loss, with both siRNAs and their p-values. Quoted with both figures rather than the larger one, because the two-fold spread between them is part of what the measurement says."},{"reference":"PMID:30531981","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30531981","reference_title":"Elucidating the contribution of ETC complexes I and II to the respirasome formation in cardiac mitochondria.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"NDUFA11 silencing induced a 72% (P < 0.01) and 63% (P < 0.05) decrease of complex III activity in cells treated with by siRNA-I and siRNA-II, respectively.","explanation":"Quantifies the complex III collapse. This is also the measurement behind the limitation recorded on this link - it is what the patients' isolated complex I deficiency does not obviously match."},{"reference":"PMID:30531981","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30531981","reference_title":"Elucidating the contribution of ETC complexes I and II to the respirasome formation in cardiac mitochondria.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Likewise, NDUFA11 knockdown markedly reduced the complex IV activity which was 71% and 72% (P < 0.05 for both) lower in cells treated with siRNA-I and siRNA-II, respectively, compared to cells treated with negative control siRNA.","explanation":"The same effect on complex IV, and unlike the respirasome readout the two siRNAs agree closely here."},{"reference":"PMID:30531981","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30531981","reference_title":"Elucidating the contribution of ETC complexes I and II to the respirasome formation in cardiac mitochondria.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Silencing of SDHC reduced enzymatic activity of complex II that, in contrast to isolated cardiac mitochondria, was not accompanied with respirasome disintegration in H9c2 cell.","explanation":"The control arm and its UNCHANGED result, quoted in the authors' own careful form - they note the contrast with isolated cardiac mitochondria rather than claiming SDHC is irrelevant everywhere. A negative control is what turns the NDUFA11 result from an observation into an attribution."},{"reference":"PMID:30531981","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30531981","reference_title":"Elucidating the contribution of ETC complexes I and II to the respirasome formation in cardiac mitochondria.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Next, we evaluated the effects of NDUFA11 and SDHC silencing on ATP synthesis and ROS production in H9c2 cells.","explanation":"Establishes that the bioenergetic readouts for this node were taken in this model on NDUFA11 knockdown."},{"reference":"PMID:30531981","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30531981","reference_title":"Elucidating the contribution of ETC complexes I and II to the respirasome formation in cardiac mitochondria.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Silencing of NDUFA11 by siRNA-I and siRNA-II was equally effective and decreased the ATP level to 48% (P < 0.01 for both)","explanation":"The quantified ATP deficit, with the agreement between the two independent siRNAs that makes it attributable to loss of NDUFA11."},{"reference":"PMID:30531981","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30531981","reference_title":"Elucidating the contribution of ETC complexes I and II to the respirasome formation in cardiac mitochondria.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Diminished ATP synthesis in NDUFA11 silenced cells was associated with the loss of ΔΨm, which was 47% (P < 0.01) and 14% (P < 0.05) lower for siRNA-1 and siRNA-2, respectively, compared to control cells","explanation":"Connects the ATP fall to membrane depolarisation. The two siRNAs differ widely here (47 versus 14 percent), so the direction is supported and the magnitude is not well constrained."},{"reference":"PMID:30531981","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30531981","reference_title":"Elucidating the contribution of ETC complexes I and II to the respirasome formation in cardiac mitochondria.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"In contrast to NDUFA11, SDHC silencing by both siRNAs did not affect the ΔΨm","explanation":"The specificity control for this readout, and the reason the membrane-potential result is treated differently from the ROS result on the same link: losing a complex II subunit did not depolarise the membrane, so the depolarisation on NDUFA11 loss is attributable to losing a proton-pumping complex rather than to reduced respiration in general. INDIRECT for the same non-human cell line reason as every other item from this paper."},{"reference":"PMID:30531981","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30531981","reference_title":"Elucidating the contribution of ETC complexes I and II to the respirasome formation in cardiac mitochondria.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Mitochondrial ROS levels were 62% and 30% higher (P < 0.01 for both) in the cells treated with NDUFA11 siRNA-1 and siRNA-2, respectively, in comparison with negative control siRNA-treated cells","explanation":"A measured rise in mitochondrial ROS, unlike the C. elegans study's statement, which reports only a potential for ROS production and is quoted elsewhere in this entry with that hedge intact."}],"evidence_text":["Our results demonstrate that NDUFA11 is involved in the respirasome assembly whereas SDHC is not a part of the respirasome.","Analysis of SCs revealed a 13% and 30% (P < 0.01 vs control for both) decrease in respirasome levels in NDUFA11 siRNA-I and siRNA-II treated cells, respectively","NDUFA11 silencing induced a 72% (P < 0.01) and 63% (P < 0.05) decrease of complex III activity in cells treated with by siRNA-I and siRNA-II, respectively.","Likewise, NDUFA11 knockdown markedly reduced the complex IV activity which was 71% and 72% (P < 0.05 for both) lower in cells treated with siRNA-I and siRNA-II, respectively, compared to cells treated with negative control siRNA.","Silencing of SDHC reduced enzymatic activity of complex II that, in contrast to isolated cardiac mitochondria, was not accompanied with respirasome disintegration in H9c2 cell.","Next, we evaluated the effects of NDUFA11 and SDHC silencing on ATP synthesis and ROS production in H9c2 cells.","Silencing of NDUFA11 by siRNA-I and siRNA-II was equally effective and decreased the ATP level to 48% (P < 0.01 for both)","Diminished ATP synthesis in NDUFA11 silenced cells was associated with the loss of ΔΨm, which was 47% (P < 0.01) and 14% (P < 0.05) lower for siRNA-1 and siRNA-2, respectively, compared to control cells","In contrast to NDUFA11, SDHC silencing by both siRNAs did not affect the ΔΨm","Mitochondrial ROS levels were 62% and 30% higher (P < 0.01 for both) in the cells treated with NDUFA11 siRNA-1 and siRNA-2, respectively, in comparison with negative control siRNA-treated cells","Establishes that this model is informative for the supercomplex node: the authors' stated conclusion is the node's claim, and it is stated against a control rather than alone.","The quantified respirasome loss, with both siRNAs and their p-values. Quoted with both figures rather than the larger one, because the two-fold spread between them is part of what the measurement says.","Quantifies the complex III collapse. This is also the measurement behind the limitation recorded on this link - it is what the patients' isolated complex I deficiency does not obviously match.","The same effect on complex IV, and unlike the respirasome readout the two siRNAs agree closely here.","The control arm and its UNCHANGED result, quoted in the authors' own careful form - they note the contrast with isolated cardiac mitochondria rather than claiming SDHC is irrelevant everywhere. A negative control is what turns the NDUFA11 result from an observation into an attribution.","Establishes that the bioenergetic readouts for this node were taken in this model on NDUFA11 knockdown.","The quantified ATP deficit, with the agreement between the two independent siRNAs that makes it attributable to loss of NDUFA11.","Connects the ATP fall to membrane depolarisation. The two siRNAs differ widely here (47 versus 14 percent), so the direction is supported and the magnitude is not well constrained.","The specificity control for this readout, and the reason the membrane-potential result is treated differently from the ROS result on the same link: losing a complex II subunit did not depolarise the membrane, so the depolarisation on NDUFA11 loss is attributable to losing a proton-pumping complex rather than to reduced respiration in general. 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The rescue establishes the molecular lesion; it says nothing about whether an affected myocardium would respond, which is the question that matters clinically and the one no cached source addresses.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0006120","label":"mitochondrial electron transport, NADH to ubiquinone","display_label":"mitochondrial electron transport, NADH to ubiquinone","url":"http://purl.obolibrary.org/obo/GO_0006120"},{"id":"GO:0006119","label":"oxidative phosphorylation","display_label":"oxidative phosphorylation","url":"http://purl.obolibrary.org/obo/GO_0006119"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[],"evidence":[{"reference":"PMID:17557076","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/17557076","reference_title":"Human CIA30 is involved in the early assembly of mitochondrial complex I and mutations in its gene cause disease.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Complementing the deficiency in patient fibroblasts with normal CIA30 using a novel lentiviral system restored steady-state complex I levels","explanation":"The rescue result itself, in the patient's own cells."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Mitochondrial_Complex_I_Deficiency_Nuclear_Type_11","model_node_id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_11.yaml:NDUFAF1 patient fibroblasts with lentiviral CIA30 complementation","focus_node_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_11:pathophysiology:Complex%20I%20Deficiency","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_11.html#pathograph","nodes":[{"id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_11.yaml:NDUFAF1 patient fibroblasts with lentiviral CIA30 complementation","kind":"experimental_model","kind_label":"NAM model","label":"NDUFAF1 patient fibroblasts with lentiviral CIA30 complementation","description":"The index patient's fibroblasts carry the disease genotype, and re-expressing wild-type CIA30 in them restored steady-state complex I. 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The 2023 patient's fibroblasts show only a mild activity reduction alongside a severe complexome defect, which is a direct demonstration that the fibroblast activity assay can under-read this disease.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0006120","label":"mitochondrial electron transport, NADH to ubiquinone","display_label":"mitochondrial electron transport, NADH to ubiquinone","url":"http://purl.obolibrary.org/obo/GO_0006120"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[],"evidence":[{"reference":"PMID:19463981","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/19463981","reference_title":"Mutations in NDUFAF3 (C3ORF60), encoding an NDUFAF4 (C6ORF66)-interacting complex I assembly protein, cause fatal neonatal mitochondrial disease.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"All patients harbored mutations in the NDUFAF3 (C3ORF60) gene, of which the pathogenic nature was assessed by NDUFAF3-GFP baculovirus complementation in fibroblasts.","explanation":"The complementation assay and the delivery method used in the founding report."},{"reference":"PMID:27986404","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/27986404","reference_title":"Mutations in mitochondrial complex I assembly factor NDUFAF3 cause Leigh syndrome.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"In a patient presenting with Leigh syndrome, which has hitherto not been described as a clinical feature of NDUFAF3 deficiency, we identified a novel homozygous variant and confirmed its pathogenicity in patient fibroblasts studies.","explanation":"The clause that pathogenicity was confirmed in patient fibroblast studies is the second, independent complementation - nine years after the founding report and in a patient with a different allele - which is what makes this model informative rather than a single result. Graded HUMAN_CLINICAL because this sentence is the report's patient-level identification statement and is graded that way at its other two uses in this file; the publication mixes a clinical case with fibroblast work, and one quoted sentence carries one grading."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Mitochondrial_Complex_I_Deficiency_Nuclear_Type_18","model_node_id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_18.yaml:NDUFAF3 patient fibroblast complementation","focus_node_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_18:pathophysiology:Isolated%20Complex%20I%20Deficiency","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_18.html#pathograph","nodes":[{"id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_18.yaml:NDUFAF3 patient fibroblast complementation","kind":"experimental_model","kind_label":"NAM model","label":"NDUFAF3 patient fibroblast complementation","description":"Fibroblasts from patients, complemented with wild-type NDUFAF3. 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There is no NDUFAF3 mouse, and no patient tissue beyond the muscle and fibroblast samples of the published cases.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_18.html#experimental-model-ndufaf3-patient-fibroblast-complementation","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_18:pathophysiology:Isolated%20Complex%20I%20Deficiency","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Isolated Complex I Deficiency","description":"Too little functioning NADH:ubiquinone oxidoreductase. The magnitude varies across the reported patients and tracks loosely with severity: 17 to 21 percent of control activity in the skeletal muscle of the child with cavitating leukoencephalopathy, against only a relatively mild reduction in the fibroblasts of the ten-year-old with the mildest reported phenotype.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_18.html#pathophysiology-isolated-complex-i-deficiency","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_18:pathophysiology:Basal%20Ganglia%20and%20Brainstem%20Injury","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Basal Ganglia and Brainstem Injury","description":"The regional pattern that gives the disease its named syndromes. One patient has Leigh syndrome. The one-year-old with cavitating leukoencephalopathy had bilaterally symmetrical signal change in the substantia nigra, medial thalamic nuclei and basal nuclei, with cavities in the cerebral white matter and corpus callosum, and raised lactate on spectroscopy in the white matter and basal nuclei. The ten-year-old had dystonia with basal ganglia abnormalities.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_18.html#pathophysiology-basal-ganglia-and-brainstem-injury","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_18:phenotype:Exercise%20Intolerance","kind":"phenotype","kind_label":"Phenotype","label":"Exercise Intolerance","description":"Progressive exercise intolerance in the ten-year-old, the muscle symptom of the disease in the one patient who lived long enough to have one described.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_18.html#phenotype-exercise-intolerance","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_18:pathophysiology:Neonatal%20and%20Infantile%20Encephalopathy%20with%20Lactic%20Acidosis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Neonatal and Infantile Encephalopathy with Lactic Acidosis","description":"The severe pole, and what most reported children have had. The gene was found in three families with severe neonatal lactic acidosis, and across the first seven reported patients the course was severe neurological disease with lactic acidosis, fatal in infancy in most. The expert-panel summary adds the features seen as that course runs: developmental regression, hypotonia and myoclonic seizures, with onset between the neonatal period and early childhood.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_18.html#pathophysiology-neonatal-and-infantile-encephalopathy-with-lactic-acidosis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_18:phenotype:Optic%20Atrophy","kind":"phenotype","kind_label":"Phenotype","label":"Optic Atrophy","description":"Optic nerve degeneration, named in the expert-panel summary of the NDUFAF3 phenotype. No individual NDUFAF3 patient's ophthalmological findings are described in the accessible literature.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_18.html#phenotype-optic-atrophy","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_18:pathophysiology:Stalled%20Complex%20I%20Assembly%20with%20Depleted%20Q-%20and%20P-Module%20Subunits","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Stalled Complex I Assembly with Depleted Q- and P-Module Subunits","description":"The holoenzyme does not complete. Two-dimensional blue-native and denaturing gels from the leukoencephalopathy patient show matrix-arm Q-module subunits (NDUFS2, NDUFS3, NDUFA9) and membrane-arm P-module subunits (NDUFB10, NDUFB11) reduced together, so the block is not confined to one module. Complexome profiling of the 2023 patient shows what piles up behind it: early membrane-arm sub-assemblies still bound to the MCIA complex. The same profiling reports a second, unusual species in that patient - free monomeric complex I still holding the MCIA complex and other assembly factors - so the holoenzyme that does form has not released its assembly machinery.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_18.html#pathophysiology-stalled-complex-i-assembly-with-depleted-q-and-p-module-subunits","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"}],"edges":[{"id":"model-link:0:model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_18.yaml:NDUFAF3 patient fibroblast complementation","source_id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_18.yaml:NDUFAF3 patient fibroblast complementation","target_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_18:pathophysiology:Isolated%20Complex%20I%20Deficiency","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Rescues","directed":false,"relationship":"RESCUES","fidelity":"HIGH","causal_link_type":null,"causal_link_type_label":null,"description":"Supplying wild-type NDUFAF3 to the patient's own cells is what localises the enzyme deficiency to this gene rather than to a coincidental variant, and it was the basis on which the founding alleles were called pathogenic.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":2},{"id":"causal:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_18:4:1","source_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_18:pathophysiology:Isolated%20Complex%20I%20Deficiency","target_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_18:pathophysiology:Basal%20Ganglia%20and%20Brainstem%20Injury","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[4].downstream[1]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"The selective vulnerability that produces Leigh syndrome, the symmetrical deep grey lesions and the dystonia. 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Graded HUMAN_CLINICAL because this sentence is the report's patient-level identification statement and is graded that way at its other two uses in this file; the publication mixes a clinical case with fibroblast work, and one quoted sentence carries one grading."}],"evidence_text":["All patients harbored mutations in the NDUFAF3 (C3ORF60) gene, of which the pathogenic nature was assessed by NDUFAF3-GFP baculovirus complementation in fibroblasts.","In a patient presenting with Leigh syndrome, which has hitherto not been described as a clinical feature of NDUFAF3 deficiency, we identified a novel homozygous variant and confirmed its pathogenicity in patient fibroblasts studies.","The complementation assay and the delivery method used in the founding report.","The clause that pathogenicity was confirmed in patient fibroblast studies is the second, independent complementation - nine years after the founding report and in a patient with a different allele - which is what makes this model informative rather than a single result. 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This is a recognised downstream signature of complex I assembly defects rather than a separate lesion, and it is recorded here because it is measured directly in this disease's patient material.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_17.html#pathophysiology-respirasome-depletion","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"}],"edges":[{"id":"model-link:0:model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_17.yaml:NDUFAF6 patient fibroblast complementation","source_id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_17.yaml:NDUFAF6 patient fibroblast complementation","target_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_17:pathophysiology:Isolated%20Complex%20I%20Deficiency","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Rescues","directed":false,"relationship":"RESCUES","fidelity":"HIGH","causal_link_type":null,"causal_link_type_label":null,"description":"Supplying the wild-type gene to the patient's own cells is what localises the enzyme deficiency to NDUFAF6 rather than to a coincidental variant, and it was the basis on which several of the reported alleles were called pathogenic.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":2},{"id":"causal:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_17:2:0","source_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_17:pathophysiology:Failure%20of%20NDUFS8%20Incorporation%20into%20the%20Complex%20I%20Q%20Module","target_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_17:pathophysiology:Isolated%20Complex%20I%20Deficiency","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Too little mature holoenzyme is produced. The cohort data make the key quantitative point that the loss is partial in every patient studied.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_17:3:0","source_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_17:pathophysiology:Impaired%20ND1%20Synthesis%20and%20Stalled%20Late-Stage%20Complex%20I%20Assembly","target_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_17:pathophysiology:Isolated%20Complex%20I%20Deficiency","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[3].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"The assembly block is what produces the enzyme deficiency, shown by the complementation that restores both 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lymphocytes.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_17:4:0","source_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_17:pathophysiology:Isolated%20Complex%20I%20Deficiency","target_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_17:pathophysiology:Respirasome%20Depletion","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[4].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Less monomeric complex I means less of it available to enter respiratory supercomplexes, with a matching accumulation of the complex III homodimer that would otherwise be bound into them.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1}]}}],"mechanism_names":["Isolated Complex I Deficiency"],"relationships":["Rescues"],"fidelities":["High"],"biological_scales":["Molecular"],"system_context_sources":["Linked mechanism biological scale"],"modeled_system_labels":["Molecular"],"biological_process_terms":[{"id":"GO:0006120","label":"mitochondrial electron transport, NADH to ubiquinone","display_label":"mitochondrial electron transport, NADH to ubiquinone","url":"http://purl.obolibrary.org/obo/GO_0006120"}],"biological_processes":["mitochondrial electron transport, NADH to ubiquinone"],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":[],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:22019594","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/22019594","reference_title":"Mutations in the gene encoding C8orf38 block complex I assembly by inhibiting production of the mitochondria-encoded subunit ND1.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Complementation with wild-type C8orf38 restored the levels of both ND1 and complex I, confirming the C8orf38 mutation as the cause of the complex I defect in the patient.","explanation":"The rescue and what it restored, in the founding functional characterisation."},{"reference":"PMID:30642748","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30642748","reference_title":"Mutations in the mitochondrial complex I assembly factor NDUFAF6 cause isolated bilateral striatal necrosis and progressive dystonia in childhood.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"By functional complementation assay, the mutant phenotype was rescued by the canonical version of the NDUFAF6.","explanation":"The independent repeat of the rescue, and the point that it is the canonical mitochondrially targeted isoform that rescues."}],"evidence_text":["Complementation with wild-type C8orf38 restored the levels of both ND1 and complex I, confirming the C8orf38 mutation as the cause of the complex I defect in the patient.","By functional complementation assay, the mutant phenotype was rescued by the canonical version of the NDUFAF6.","The rescue and what it restored, in the founding functional characterisation.","The independent repeat of the rescue, and the point that it is the canonical mitochondrially targeted isoform that rescues."],"evidence_status":"Evidence recorded","metadata_completeness":30,"metadata_present":["Model category","Modeled mechanism","Evidence"],"metadata_missing":["NAMO class","Organism","Anatomy","Cell type","Cell source","Culture system","Publication"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_17.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_17.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_17.html#experimental-model-ndufaf6-patient-fibroblast-complementation","source_anchor":"experimental-model-ndufaf6-patient-fibroblast-complementation"},{"id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_34.yaml:NDUFAF8 patient fibroblast complementation","name":"NDUFAF8 patient fibroblast complementation","description":"Fibroblasts from the three Leigh-syndrome subjects, transduced with wild-type NDUFAF8 cDNA. This is the experiment that converted a candidate gene into a disease gene, and it is the only functional work reported in cells from a patient with this disorder. There is no NDUFAF8 animal model, no knockout cell line reported in a disease context, and no patient tissue.","notes":null,"context_id":"disorder:Mitochondrial_Complex_I_Deficiency_Nuclear_Type_34","context_kind":"Disorder","disease_name":"Mitochondrial Complex I Deficiency, Nuclear Type 34","disease_synonyms":["MC1DN34","NDUFAF8-related mitochondrial complex I deficiency","NDUFAF8 deficiency","C17orf89 deficiency"],"disease_term":{"id":"MONDO:0032910","label":"mitochondrial complex I deficiency, nuclear type 34","display_label":"Mitochondrial complex I deficiency, nuclear type 34","url":"http://purl.obolibrary.org/obo/MONDO_0032910"},"experimental_model_type":"PRIMARY_CELL_CULTURE","experimental_model_type_label":"Primary-cell culture","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[{"id":"CL:0000057","label":"fibroblast","display_label":"patient dermal fibroblast","url":"http://purl.obolibrary.org/obo/CL_0000057"}],"linked_cell_type_labels":["fibroblast"],"cell_types":[{"id":"CL:0000057","label":"fibroblast","display_label":"patient dermal fibroblast","url":"http://purl.obolibrary.org/obo/CL_0000057"}],"cell_type_labels":["fibroblast"],"conditions":[],"cell_source":null,"source_category":"Primary / biopsy-derived","culture_system":null,"publication":null,"publication_url":null,"mechanisms":[{"target":"Isolated Complex I Deficiency","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_34.html#pathophysiology-isolated-complex-i-deficiency","relationship":"RESCUES","relationship_label":"Rescues","fidelity":"HIGH","fidelity_label":"High","description":"Supplying wild-type NDUFAF8 corrected both the assembly defect and the biochemical deficiency in the patients' own cells, which excludes a coincidental variant and localises the deficit to this gene.","limitations":"Fibroblasts are neither brain nor retinal ganglion cell, and neither affected tissue has been studied. The rescue establishes causality; it says nothing about why the basal ganglia or the optic nerve are the organs that fail, nor about why the same gene produces two such different clinical pictures.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[{"id":"CL:0000057","label":"fibroblast","display_label":"patient dermal fibroblast","url":"http://purl.obolibrary.org/obo/CL_0000057"}],"biological_processes":[{"id":"GO:0006120","label":"mitochondrial electron transport, NADH to ubiquinone","display_label":"mitochondrial electron transport, NADH to ubiquinone","url":"http://purl.obolibrary.org/obo/GO_0006120"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Complex I assembly and enzyme activity after wild-type NDUFAF8 expression","description":null,"target":"Isolated Complex I Deficiency","direction":"RESTORED","interpretation":"Both the assembly defect and the biochemical deficiency improving on complementation is the criterion the authors used to call the variants causal.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:31866046","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/31866046","reference_title":"Pathogenic Bi-allelic Mutations in NDUFAF8 Cause Leigh Syndrome with an Isolated Complex I Deficiency.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Subject fibroblasts were found to express a complex I deficiency, and lentiviral transduction with wild-type NDUFAF8-cDNA ameliorated both the assembly defect and the biochemical deficiency.","explanation":"The rescue measurement underlying this readout."}],"notes":null}],"evidence":[{"reference":"PMID:31866046","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/31866046","reference_title":"Pathogenic Bi-allelic Mutations in NDUFAF8 Cause Leigh Syndrome with an Isolated Complex I Deficiency.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Complexome profiling of subject fibroblasts demonstrated a complex I assembly defect, and the stalled assembly intermediates corroborate the role of NDUFAF8 in early complex I assembly.","explanation":"Establishes that the patient fibroblast reproduces the assembly lesion this node describes, which is what makes the model informative for it."},{"reference":"PMID:31866046","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/31866046","reference_title":"Pathogenic Bi-allelic Mutations in NDUFAF8 Cause Leigh Syndrome with an Isolated Complex I Deficiency.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Subject fibroblasts were found to express a complex I deficiency, and lentiviral transduction with wild-type NDUFAF8-cDNA ameliorated both the assembly defect and the biochemical deficiency.","explanation":"The rescue measurement underlying this readout."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Mitochondrial_Complex_I_Deficiency_Nuclear_Type_34","model_node_id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_34.yaml:NDUFAF8 patient fibroblast complementation","focus_node_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_34:pathophysiology:Isolated%20Complex%20I%20Deficiency","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_34.html#pathograph","nodes":[{"id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_34.yaml:NDUFAF8 patient fibroblast complementation","kind":"experimental_model","kind_label":"NAM model","label":"NDUFAF8 patient fibroblast complementation","description":"Fibroblasts from the three Leigh-syndrome subjects, transduced with wild-type NDUFAF8 cDNA. 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Patient fibroblasts express a complex I deficiency; the deficiency is isolated, meaning the other respiratory-chain complexes are spared, which is what an assembly factor dedicated to complex I predicts and what distinguishes this from the combined deficiencies caused by defects in mitochondrial gene expression. Lentiviral transduction with wild-type NDUFAF8 cDNA corrected both the assembly defect and the biochemical deficiency, which is the experiment that makes the gene causal rather than merely associated.\nConformance note: the module node pairs decreased oxidative phosphorylation with increased reactive oxygen species. Only the first half is evidenced here - no reactive-oxygen measurement has been reported in an NDUFAF8 patient - and the ROS arm is not asserted. The module's upstream node, age-related mitochondrial damage and mtDNA mutation, does not apply to a primary nuclear-gene assembly defect, so conformance is declared at this node alone.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_34.html#pathophysiology-isolated-complex-i-deficiency","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_34:pathophysiology:Leigh-Syndrome%20Encephalopathy","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Leigh-Syndrome Encephalopathy","description":"The 2020 pole of the phenotype. All three subjects in the defining cohort carried a clinical diagnosis of Leigh syndrome - the commonest neurological presentation of paediatric mitochondrial disease, defined by symmetrical basal-ganglia, thalamic and brainstem lesions on neuroimaging together with loss of motor skills and delayed milestones.\nA scope note that matters for how this node should be read. The subjects' Leigh diagnosis is directly stated in the source; the lesion distribution and developmental features are quoted from the source's definition of Leigh syndrome rather than from a description of these three children. The diagnosis entails those features, which is why they are recorded here, but no per-patient imaging or developmental description is available in the cached record. The `phenotypes:` block reflects that distinction: it curates the Leigh diagnosis, not a list of individually observed neurological signs.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_34.html#pathophysiology-leigh-syndrome-encephalopathy","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_34:pathophysiology:Retinal%20Ganglion%20Cell%20and%20Optic%20Nerve%20Degeneration","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Retinal Ganglion Cell and Optic Nerve Degeneration","description":"The 2026 pole of the phenotype. Six patients with biallelic NDUFAF8 variants presented with optic atrophy, five of them with optic atrophy and nothing else; the sixth also had cerebellar ataxia and nystagmus. In six of the thirteen patients across the four assembly-factor genes in that cohort the vision loss was subacute, which is the pattern of Leber hereditary optic neuropathy, and NDUFAF8 was associated with the autosomal-recessive LHON phenotype for the first time.\nMarked PROVISIONAL rather than ESTABLISHED because the *cellular* claim in the node title is an inference. What was observed is optic atrophy in patients; retinal ganglion cell loss is the accepted substrate of optic atrophy in the mitochondrial optic neuropathies but was not measured in these patients, and no NDUFAF8 tissue has been examined.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_34.html#pathophysiology-retinal-ganglion-cell-and-optic-nerve-degeneration","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_34:pathophysiology:Stalled%20Early%20Complex%20I%20Assembly","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Stalled Early Complex I Assembly","description":"Complex I is built stepwise from modular intermediates, and where a defect stalls that process is visible directly by complexome profiling. In NDUFAF8 patient fibroblasts the profile shows an assembly defect whose stalled intermediates place NDUFAF8's role early - consistent with the module's substrate being a core Q-module subunit rather than a late accessory addition.\nThis is the node that separates MC1DN34 from a subunit deficiency. A missing subunit yields an enzyme that is assembled but incomplete or inactive; a missing early assembly factor yields an enzyme that never gets past an intermediate.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_34.html#pathophysiology-stalled-early-complex-i-assembly","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"}],"edges":[{"id":"model-link:0:model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_34.yaml:NDUFAF8 patient fibroblast complementation","source_id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_34.yaml:NDUFAF8 patient fibroblast complementation","target_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_34:pathophysiology:Isolated%20Complex%20I%20Deficiency","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Rescues","directed":false,"relationship":"RESCUES","fidelity":"HIGH","causal_link_type":null,"causal_link_type_label":null,"description":"Supplying wild-type NDUFAF8 corrected both the assembly defect and the biochemical deficiency in the patients' own cells, which excludes a coincidental variant and localises the deficit to this gene.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_34:4:1","source_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_34:pathophysiology:Isolated%20Complex%20I%20Deficiency","target_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_34:pathophysiology:Leigh-Syndrome%20Encephalopathy","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[4].downstream[1]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"The route from a generalised bioenergetic deficit to the specific symmetrical brainstem and basal-ganglia lesions of Leigh syndrome is not established for NDUFAF8 or for complex I deficiency as a class.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_34:4:0","source_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_34:pathophysiology:Isolated%20Complex%20I%20Deficiency","target_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_34:pathophysiology:Retinal%20Ganglion%20Cell%20and%20Optic%20Nerve%20Degeneration","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[4].downstream[0]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"Why complex I failure selects retinal ganglion cells is the central unsolved question of the inherited optic neuropathies generally, and no NDUFAF8-specific work addresses it. 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It also has no tissue context, so it cannot speak to why basal ganglia, heart and muscle are the tissues that fail.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0032981","label":"mitochondrial respiratory chain complex I assembly","display_label":"mitochondrial respiratory chain complex I assembly","url":"http://purl.obolibrary.org/obo/GO_0032981"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Assembled complex I in the NDUFB8 knockout line","description":null,"target":"Failure of Complex I Holoenzyme Assembly","direction":"ABOLISHED","interpretation":"No complex I assembly is detectable in cells lacking NDUFB8.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:33233646","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33233646","reference_title":"Analysis of Human Mutations in the Supernumerary Subunits of Complex I.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"In a knockout strain of cultured human cells, the loss of NDUFB8 resulted in no assembly of complex I","explanation":"The readout, reported as a complete absence of assembly."}],"notes":null}],"evidence":[{"reference":"PMID:27626371","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/27626371","reference_title":"Accessory subunits are integral for assembly and function of human mitochondrial complex I.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Here we use gene editing to generate human knockout cell lines for each accessory subunit.","explanation":"Establishes the model system - a per-subunit knockout panel - that the NDUFB8 result comes from."},{"reference":"PMID:33233646","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33233646","reference_title":"Analysis of Human Mutations in the Supernumerary Subunits of Complex I.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"In a knockout strain of cultured human cells, the loss of NDUFB8 resulted in no assembly of complex I","explanation":"The readout, reported as a complete absence of assembly."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Mitochondrial_Complex_I_Deficiency_Nuclear_Type_32","model_node_id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_32.yaml:NDUFB8 knockout human cell line","focus_node_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_32:pathophysiology:Failure%20of%20Complex%20I%20Holoenzyme%20Assembly","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_32.html#pathograph","nodes":[{"id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_32.yaml:NDUFB8 knockout human cell line","kind":"experimental_model","kind_label":"NAM model","label":"NDUFB8 knockout human cell line","description":"A CRISPR knockout of NDUFB8 in a human cell line, generated as part of a systematic survey of all 31 complex I accessory subunits. 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The general rule established by that survey - that losing one subunit destabilises the other subunits of its own structural module - is the mechanism by which a single missing brace propagates into a whole-enzyme failure.\nThe knockout evidence is a complete null; the patient alleles are not, which is why this node is written as a failure of assembly rather than an absence of the enzyme, and why patients retain measurable residual activity.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_32.html#pathophysiology-failure-of-complex-i-holoenzyme-assembly","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_32:pathophysiology:Depletion%20of%20NDUFB8%20from%20the%20Complex%20I%20Distal%20Membrane%20Arm","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Depletion of NDUFB8 from the Complex I Distal Membrane Arm","description":"NDUFB8 sits at the distal, proton-pumping end of complex I in the ND5 module, spanning the inner membrane once with its N-terminus in the matrix and its C-terminus in the intermembrane space. Its defining structural role is to clamp the long lateral helix of the core subunit ND5; on the matrix side it also contacts ND5 and NDUFB4 and, more weakly, ND4 and NDUFB9, and on the intermembrane-space side NDUFB7 and NDUFB10. With NDUFB3 and NDUFB6 it encloses the distal end of the enzyme. Losing it therefore removes a structural brace at a module interface rather than a catalytic component.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_32.html#pathophysiology-depletion-of-ndufb8-from-the-complex-i-distal-membrane-arm","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_32:pathophysiology:Isolated%20Complex%20I%20Enzyme%20Deficiency","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Isolated Complex I Enzyme Deficiency","description":"The measurable consequence in patient tissue: a decrease in complex I enzymatic activity in both muscle and fibroblasts, with the other respiratory chain complexes spared. 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This is the experiment that made MC1DN24 a disease rather than a candidate association, and it is the only functional work published in cells from a patient with this disorder. Note the deliberate narrowness of that claim: NDUFB9 has been studied functionally in human cells elsewhere, in breast-cancer and adipogenesis models, but none of that work involves a patient or bears on the disease.","notes":null,"context_id":"disorder:Mitochondrial_Complex_I_Deficiency_Nuclear_Type_24","context_kind":"Disorder","disease_name":"Mitochondrial Complex I Deficiency, Nuclear Type 24","disease_synonyms":["MC1DN24","NDUFB9-related mitochondrial complex I deficiency","NDUFB9 deficiency"],"disease_term":{"id":"MONDO:0032628","label":"mitochondrial complex I deficiency, nuclear type 24","display_label":"Mitochondrial complex I deficiency, nuclear type 24","url":"http://purl.obolibrary.org/obo/MONDO_0032628"},"experimental_model_type":"PRIMARY_CELL_CULTURE","experimental_model_type_label":"Primary-cell culture","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":null,"source_category":"Primary / biopsy-derived","culture_system":null,"publication":null,"publication_url":null,"mechanisms":[{"target":"Reduced Complex I Amount and Activity","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_24.html#pathophysiology-reduced-complex-i-amount-and-activity","relationship":"RESCUES","relationship_label":"Rescues","fidelity":"HIGH","fidelity_label":"High","description":"Restoring wild-type NDUFB9 restored both the amount and the activity of complex I in the patient's own cells, which excludes a coincidental variant and localises the deficit to this gene.","limitations":"Fibroblasts are not the affected tissue, and no affected tissue was studied. The rescue establishes causality; it says nothing about which organ fails in the patient or why.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0006120","label":"mitochondrial electron transport, NADH to ubiquinone","display_label":"mitochondrial electron transport, NADH to ubiquinone","url":"http://purl.obolibrary.org/obo/GO_0006120"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Complex I amount and activity after wild-type NDUFB9 expression","description":null,"target":"Reduced Complex I Amount and Activity","direction":"RESTORED","interpretation":"Both measures returning towards normal on complementation is the criterion the authors used to call the variant causal.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:22200994","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/22200994","reference_title":"Mutation screening of 75 candidate genes in 152 complex I deficiency cases identifies pathogenic variants in 16 genes including NDUFB9.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"These features were rescued by expression of wild-type NDUFB9 in patient-derived fibroblasts.","explanation":"The rescue measurement underlying this readout."}],"notes":null}],"evidence":[{"reference":"PMID:22200994","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/22200994","reference_title":"Mutation screening of 75 candidate genes in 152 complex I deficiency cases identifies pathogenic variants in 16 genes including NDUFB9.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The causal role of a new disease allele was confirmed by functional complementation assays.","explanation":"Establishes complementation as the method by which causality was assigned."},{"reference":"PMID:22200994","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/22200994","reference_title":"Mutation screening of 75 candidate genes in 152 complex I deficiency cases identifies pathogenic variants in 16 genes including NDUFB9.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"These features were rescued by expression of wild-type NDUFB9 in patient-derived fibroblasts.","explanation":"The rescue measurement underlying this readout."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Mitochondrial_Complex_I_Deficiency_Nuclear_Type_24","model_node_id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_24.yaml:NDUFB9 patient fibroblast complementation","focus_node_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_24:pathophysiology:Reduced%20Complex%20I%20Amount%20and%20Activity","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_24.html#pathograph","nodes":[{"id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_24.yaml:NDUFB9 patient fibroblast complementation","kind":"experimental_model","kind_label":"NAM model","label":"NDUFB9 patient fibroblast complementation","description":"Patient-derived fibroblasts transduced with wild-type NDUFB9. This is the experiment that made MC1DN24 a disease rather than a candidate association, and it is the only functional work published in cells from a patient with this disorder. Note the deliberate narrowness of that claim: NDUFB9 has been studied functionally in human cells elsewhere, in breast-cancer and adipogenesis models, but none of that work involves a patient or bears on the disease.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_24.html#experimental-model-ndufb9-patient-fibroblast-complementation","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_24:pathophysiology:Reduced%20Complex%20I%20Amount%20and%20Activity","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced Complex I Amount and Activity","description":"The measured endpoint, and the best-evidenced statement in this entry. Tagged MOLECULAR rather than CELLULAR on the schema's own terms: the substrate is an enzyme complex and the claim is that it is functionally deficient and reduced in abundance, which is the MOLECULAR definition verbatim (\"an enzyme is functionally deficient ... substrate is a molecule, complex, or genetic element\"). The measurement happens in cells, but the thing measured is the complex. both the amount and the activity of complex I are reduced in the patient, and both are restored by expressing wild-type NDUFB9 in the patient's fibroblasts. That both fall together is the signature of an assembly or stability defect rather than a catalytic one - a defective core subunit would be expected to reduce activity while leaving a normal or near-normal amount of assembled enzyme.\nConformance note: the module pairs decreased oxidative phosphorylation with increased reactive oxygen species. Decreased complex I amount and activity is directly evidenced here; the reactive-oxygen-species arm is not measured in this patient and is not asserted. The module's upstream node, age-related mitochondrial damage and mtDNA mutation, does not apply to a primary nuclear-gene subunit defect, so conformance is declared at this node alone - which is the substitution the module's own description invites for primary nuclear respiratory-chain defects.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_24.html#pathophysiology-reduced-complex-i-amount-and-activity","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_24:pathophysiology:Impaired%20Respirasome%20Oligomerization","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Respirasome Oligomerization","description":"A second, structurally motivated role that has never been tested in a patient. Two independent cryo-electron microscopy structures of the porcine heart respirasome - the 1.7-megadalton supercomplex of one complex I, a complex III dimer and one complex IV - place NDUFB9 among the accessory subunits that directly mediate the oligomerization of the individual complexes into the supercomplex. Losing NDUFB9 should therefore impair supercomplex formation as well as complex I assembly.\nThis node is HYPOTHETICAL in the strict sense: it is an inference from a static structure to a functional consequence, with no supporting measurement in any NDUFB9-deficient cell. It is curated rather than omitted because it is a testable prediction that distinguishes this subunit from most other complex I accessory subunits, and because a respirasome assay is an obvious next experiment that nobody appears to have run.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_24.html#pathophysiology-impaired-respirasome-oligomerization","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"HYPOTHETICAL","mechanism_confidence_label":"Hypothetical"},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_24:pathophysiology:Loss%20of%20the%20NDUFB9-Acyl%20Carrier%20Protein%20Module","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Loss of the NDUFB9-Acyl Carrier Protein Module","description":"The mechanistic account of why losing an accessory subunit disassembles the enzyme. NDUFB9 is LYRM3, a leucine-tyrosine-arginine motif protein, and its role is to anchor a copy of mitochondrial acyl carrier protein - the central element of mitochondrial fatty acid synthesis - to the complex I membrane arm. In Yarrowia lipolytica the two ACP-LYRM modules have a division of labour that maps onto this disease well: the ACPM1-LYRM6 (NDUFA6) module is essential for complex I activity, while the ACPM2-LYRM3 (NDUFB9) module is essential for assembly and stability. A patient with reduced NDUFB9 should therefore lose complex I amount, not just complex I function - which is exactly what was measured.\nMarked HYPOTHETICAL despite that agreement, because the module assignment comes entirely from a yeast enzyme that carries two ACPMs where the mammalian enzyme carries one, and no study has tested ACP anchoring in an NDUFB9 patient or in any human cell. The correspondence between the yeast prediction and the patient measurement is suggestive, not demonstrative.\nThat said, the broader assembly-or-stability claim does have patient-level corroboration waiting behind the paywall, and it belongs here as an uncited lead. The deep-research report records that NDUFS1, NDUFS3, NDUFB8 and NDUFA9 were all reduced in the patient's fibroblasts and all restored by wild-type NDUFB9. A single accessory-subunit lesion depleting several other subunits, reversibly, is the signature of failed assembly rather than failed catalysis - and unlike the yeast module assignment it is a human-cell observation. It is not curated as evidence because it is not snippet-verifiable; what stays HYPOTHETICAL is specifically the ACP-anchoring mechanism, not the assembly phenotype it is invoked to explain.\nA further consequence worth recording: the anchoring depends on a long acyl chain on the ACP phosphopantetheine cofactor, so this module is a point at which complex I biogenesis is coupled to mitochondrial fatty acid synthesis rather than to respiration.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_24.html#pathophysiology-loss-of-the-ndufb9-acyl-carrier-protein-module","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"HYPOTHETICAL","mechanism_confidence_label":"Hypothetical"}],"edges":[{"id":"model-link:0:model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_24.yaml:NDUFB9 patient 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Examples: HepG2, A549, Caco-2, etc.","namo_docs_url":"https://monarch-initiative.github.io/namo/elements/CellLineModel/","namo_ontology_url":"https://w3id.org/monarch-initiative/namo/CellLineModel","namo_mapping_basis":"Safe mapping from DisMech category","namo_class_in_schema":true,"namo_schema_status":"Defined in NAMO schema used for this build","modality":"Cellular system","organism":{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},"organism_label":"Homo sapiens","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":"Immortalized human embryonic kidney 293, NDUFS2 CRISPR/Cas9 knockout","source_category":"Immortalized / cell line","culture_system":null,"publication":"PMID:33744462","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/33744462","mechanisms":[{"target":"Isolated Complex I Deficiency and Bioenergetic Failure","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_6.html#pathophysiology-isolated-complex-i-deficiency-and-bioenergetic-failure","relationship":"RECAPITULATES","relationship_label":"Recapitulates","fidelity":"MODERATE","fidelity_label":"Moderate","description":"Knockout reproduces the complete cellular phenotype this node asserts, including the compensatory rise in complex II respiration that follows from complex II being the one complex with no mitochondrially encoded subunits.","limitations":"Embryonic kidney cells are neither neural, cardiac nor hepatic, so nothing in this model addresses why those three tissues fail in patients while others do not. A complete knockout is also a more severe perturbation than the missense alleles that cause human disease, in which residual enzyme is present.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0006119","label":"oxidative phosphorylation","display_label":"oxidative phosphorylation","url":"http://purl.obolibrary.org/obo/GO_0006119"},{"id":"GO:0006979","label":"response to oxidative stress","display_label":"response to oxidative stress","url":"http://purl.obolibrary.org/obo/GO_0006979"},{"id":"GO:0006915","label":"apoptotic process","display_label":"apoptotic process","url":"http://purl.obolibrary.org/obo/GO_0006915"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Complex I specific respiration, ATP pool and cell growth","description":null,"target":"Isolated Complex I Deficiency and Bioenergetic Failure","direction":"DECREASED","interpretation":"All three fall on knockout, alongside glycolytic capacity and membrane integrity.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:33744462","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33744462","reference_title":"Complex I protein NDUFS2 is vital for growth, ROS generation, membrane integrity, apoptosis, and mitochondrial energetics.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Disruption of NDUFS2 significantly decreased cell growth in medium, Complex I specific respiration, glycolytic capacity, ATP pool and cell-membrane integrity","explanation":"Reports the measurements and their direction."}],"notes":null},{"name":"Reactive oxygen species, apoptosis and complex II respiration","description":null,"target":"Isolated Complex I Deficiency and Bioenergetic Failure","direction":"INCREASED","interpretation":"All rise on knockout. 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It was used both to characterise the consequences of losing the subunit and as a screening system, in which idebenone partially restored the bioenergetic phenotype.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_6.html#experimental-model-ndufs2-crispr-knockout-hek293-cell-line","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_6:pathophysiology:Isolated%20Complex%20I%20Deficiency%20and%20Bioenergetic%20Failure","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Isolated Complex I Deficiency and Bioenergetic Failure","description":"The cellular endpoint, and it is not only an energy deficit. A CRISPR knockout of NDUFS2 in human embryonic kidney cells reduces growth, complex I-specific respiration, glycolytic capacity, ATP pool and membrane integrity, while increasing reactive oxygen species production, apoptosis and necrosis. Complex II respiration rises, which is the expected compensatory shift when the complex I entry point to the chain is blocked and complex II is intact.\nIn an ndufs2 knockout zebrafish, complex I enzyme activity falls by 80 percent and unbiased metabolomics shows raised lactate, raised tricarboxylic acid cycle intermediates and raised acylcarnitines, so the block propagates into fatty acid oxidation and the cycle as well as into oxidative phosphorylation.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_6.html#pathophysiology-isolated-complex-i-deficiency-and-bioenergetic-failure","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_6:pathophysiology:Complex%20I%20Assembly%20Disruption","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Complex I Assembly Disruption","description":"The second, structural arm. Complex I has 45 subunits, seven encoded in mitochondrial DNA and 38 imported, and many of the disease variants reported across its peripheral core subunits fall at subunit interfaces. Modelling seventeen human variant positions as thirty-one mutants in the homologous Escherichia coli enzyme produced a range of reduced activity, and assembly assays, time-delayed expression and co-immunoprecipitation showed that assembly was disrupted.\nThe per-allele results are what make this node useful rather than generic, and they split the NDUFS2 alleles in two. Modelled R228Q showed a severe assembly defect: NuoCD and NuoI were no longer co-immunoprecipitated with NuoG. Modelled R138Q and Y141C did the opposite, retaining greatly diminished activity even when assembled normally. So the same subunit produces assembly lesions and catalytic lesions depending on which residue is hit, and the two arms of this entry are allele-dependent rather than competing accounts of one lesion.\nWhat keeps this PROVISIONAL is the system rather than the specificity. The work was done in a homologous bacterial enzyme, with human residues mapped onto their E. coli equivalents, so the assembly pathway is analogous rather than identical and the human consequence is inferred.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_6.html#pathophysiology-complex-i-assembly-disruption","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_6:pathophysiology:Lactic%20Acidosis%20and%20Multisystem%20Metabolic%20Decompensation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Lactic Acidosis and Multisystem Metabolic Decompensation","description":"The systemic expression of the block. Lactic acidosis is one of the three features that define the fatal neonatal presentation of mitochondrial disease, alongside neuromuscular dysfunction and hepatic failure. In the zebrafish knockout the same metabolic picture appears with an addition worth noting: one-carbon metabolism is dysregulated, and the same signature was seen in a missense ndufs2 mutant nematode and in two human complex I-deficient fibroblast lines stressed in galactose, so it is not an artefact of one species.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_6.html#pathophysiology-lactic-acidosis-and-multisystem-metabolic-decompensation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_6:pathophysiology:Loss%20of%20the%20N2%20Iron-Sulfur%20Cluster%20and%20Quinone%20Reduction","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Loss of the N2 Iron-Sulfur Cluster and Quinone Reduction","description":"The catalytic arm of the lesion, and the more precisely characterised of the two. N2 is the last iron-sulfur cluster in the electron relay and the one that reduces ubiquinone. It sits at the NDUFS2-NDUFS7 interface, ligated by four cysteines in NDUFS7 and positioned about 12 angstroms above the quinone-binding site, with NDUFS2 residues forming its second coordination sphere. NDUFS2 therefore controls the cluster without holding it, which is what makes an NDUFS2 defect able to remove it. A conserved arginine near the cluster, which is post-translationally dimethylated, turns out to be required for the cluster to form or to remain stable: substituting it abolishes quinone-reductase activity, the N2 signature disappears from the electron paramagnetic resonance spectrum, and cryo-electron microscopy shows the cubane cluster simply absent from an otherwise intact enzyme. The same substitution also disorders nearby elements of the quinone-binding site.\nThat last point is what makes this node worth separating from the assembly node, but the claim it licenses is narrower than it first appears. What the structure shows is that a particle which does assemble can be structurally native-like and catalytically dead. It does not show that the amount of enzyme is normal: in the same experiments, complex I content fell to about 40 percent and 25 percent of wild type for the two substitutions, and the authors state plainly that mutations of this residue impair assembly and stability as well. R121 is therefore a residue that hits both arms of this entry at once, which is consistent with the allele-dependent picture rather than an exception to it.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_6.html#pathophysiology-loss-of-the-n2-iron-sulfur-cluster-and-quinone-reduction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"}],"edges":[{"id":"model-link:0:model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_6.yaml:NDUFS2 CRISPR knockout HEK293 cell line","source_id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_6.yaml:NDUFS2 CRISPR knockout HEK293 cell line","target_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_6:pathophysiology:Isolated%20Complex%20I%20Deficiency%20and%20Bioenergetic%20Failure","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"Knockout reproduces the complete cellular phenotype this node asserts, including the compensatory rise in complex II respiration that follows from complex II being the one complex with no mitochondrially encoded subunits.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_6:2:0","source_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_6:pathophysiology:Complex%20I%20Assembly%20Disruption","target_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_6:pathophysiology:Isolated%20Complex%20I%20Deficiency%20and%20Bioenergetic%20Failure","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"An enzyme that does not assemble cannot function, independently of whether its catalytic centre is intact.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_6:3:0","source_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_6:pathophysiology:Isolated%20Complex%20I%20Deficiency%20and%20Bioenergetic%20Failure","target_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_6:pathophysiology:Lactic%20Acidosis%20and%20Multisystem%20Metabolic%20Decompensation","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[3].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Failure of oxidative phosphorylation forces reliance on glycolysis and accumulates the intermediates that cannot be oxidised.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_6:1:0","source_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_6:pathophysiology:Loss%20of%20the%20N2%20Iron-Sulfur%20Cluster%20and%20Quinone%20Reduction","target_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_6:pathophysiology:Isolated%20Complex%20I%20Deficiency%20and%20Bioenergetic%20Failure","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"An enzyme that cannot reduce ubiquinone cannot support electron transport through complex I, whatever its abundance.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1}]}}],"mechanism_names":["Isolated Complex I Deficiency and Bioenergetic Failure"],"relationships":["Recapitulates"],"fidelities":["Moderate"],"biological_scales":["Cellular"],"system_context_sources":["Linked mechanism biological scale"],"modeled_system_labels":["Cellular"],"biological_process_terms":[{"id":"GO:0006119","label":"oxidative phosphorylation","display_label":"oxidative phosphorylation","url":"http://purl.obolibrary.org/obo/GO_0006119"},{"id":"GO:0006979","label":"response to oxidative stress","display_label":"response to oxidative stress","url":"http://purl.obolibrary.org/obo/GO_0006979"},{"id":"GO:0006915","label":"apoptotic process","display_label":"apoptotic process","url":"http://purl.obolibrary.org/obo/GO_0006915"}],"biological_processes":["oxidative phosphorylation","response to oxidative stress","apoptotic process"],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":["Complex I specific respiration, ATP pool and cell growth","Reactive oxygen species, apoptosis and complex II respiration","Growth, ATP pool and oxygen consumption after idebenone treatment"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:33744462","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33744462","reference_title":"Complex I protein NDUFS2 is vital for growth, ROS generation, membrane integrity, apoptosis, and mitochondrial energetics.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"This is the first report to use CRISPR/Cas9 approach to construct a knockout NDUFS2 cell line and use the constructed mutant to evaluate the efficacy of a known mitochondrial therapeutic to enhance bioenergetic capacity.","explanation":"Establishes the model and the purpose it was built for."},{"reference":"PMID:33744462","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33744462","reference_title":"Complex I protein NDUFS2 is vital for growth, ROS generation, membrane integrity, apoptosis, and mitochondrial energetics.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Disruption of NDUFS2 significantly decreased cell growth in medium, Complex I specific respiration, glycolytic capacity, ATP pool and cell-membrane integrity","explanation":"Reports the measurements and their direction."},{"reference":"PMID:33744462","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33744462","reference_title":"Complex I protein NDUFS2 is vital for growth, ROS generation, membrane integrity, apoptosis, and mitochondrial energetics.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"but significantly increased Complex II respiration, ROS generation, apoptosis, and necrosis","explanation":"Reports the measurements that rise, including the compensatory complex II shift."},{"reference":"PMID:33744462","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33744462","reference_title":"Complex I protein NDUFS2 is vital for growth, ROS generation, membrane integrity, apoptosis, and mitochondrial energetics.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Treatment with idebenone, a clinical benzoquinone currently being investigated in other indications, partially restored growth, ATP pool, and oxygen consumption of the mutant.","explanation":"Reports the rescue and its extent."}],"evidence_text":["This is the first report to use CRISPR/Cas9 approach to construct a knockout NDUFS2 cell line and use the constructed mutant to evaluate the efficacy of a known mitochondrial therapeutic to enhance bioenergetic capacity.","Disruption of NDUFS2 significantly decreased cell growth in medium, Complex I specific respiration, glycolytic capacity, ATP pool and cell-membrane integrity","but significantly increased Complex II respiration, ROS generation, apoptosis, and necrosis","Treatment with idebenone, a clinical benzoquinone currently being investigated in other indications, partially restored growth, ATP pool, and oxygen consumption of the mutant.","Establishes the model and the purpose it was built for.","Reports the measurements and their direction.","Reports the measurements that rise, including the compensatory complex II shift.","Reports the rescue and its extent."],"evidence_status":"Evidence recorded","metadata_completeness":70,"metadata_present":["Model category","NAMO class","Organism","Cell source","Modeled mechanism","Publication","Evidence"],"metadata_missing":["Anatomy","Cell type","Culture system"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_6.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_6.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_6.html#experimental-model-ndufs2-crispr-knockout-hek293-cell-line","source_anchor":"experimental-model-ndufs2-crispr-knockout-hek293-cell-line"},{"id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_1.yaml:NDUFS4 knockout human iPSC line","name":"NDUFS4 knockout human iPSC line","description":"CRISPR-Cas9 knockout of NDUFS4 in human induced pluripotent stem cells, with isogenic controls. Its value is the comparator: patient fibroblast lines differ from controls in their whole genetic background, whereas an isogenic knockout differs at one locus. The limitation the authors state themselves is that undifferentiated iPSCs cannot reproduce the cellular dynamics of the disease, so this is a redox and metabolic platform rather than a model of the encephalopathy.\n`experimental_model_type` is OTHER rather than IPSC_DERIVED_MODEL on purpose. That value is defined as a *differentiated* model derived from induced pluripotent stem cells, and this one is deliberately undifferentiated, which is exactly what the authors' own caveat is about. CELL_LINE does not fit either, being defined for immortalized lines. OTHER is the accurate choice here rather than a placeholder.","notes":null,"context_id":"disorder:Mitochondrial_Complex_I_Deficiency_Nuclear_Type_1","context_kind":"Disorder","disease_name":"Mitochondrial Complex I Deficiency, Nuclear Type 1","disease_synonyms":["MC1DN1","NDUFS4 deficiency","NDUFS4-related mitochondrial complex I deficiency","mitochondrial complex I deficiency due to NDUFS4 mutation","NADH-coenzyme Q reductase deficiency, nuclear type 1"],"disease_term":{"id":"MONDO:0100224","label":"mitochondrial complex I deficiency, nuclear type 1","display_label":"mitochondrial complex I deficiency, nuclear type 1","url":"http://purl.obolibrary.org/obo/MONDO_0100224"},"experimental_model_type":"OTHER","experimental_model_type_label":"Other","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":null,"source_category":null,"culture_system":null,"publication":null,"publication_url":null,"mechanisms":[{"target":"Reductive Stress and Bioenergetic Failure","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_1.html#pathophysiology-reductive-stress-and-bioenergetic-failure","relationship":"RECAPITULATES","relationship_label":"Recapitulates","fidelity":"MODERATE","fidelity_label":"Moderate","description":"Elevated NADH/NAD+ with about half the complex I activity of isogenic controls.","limitations":"Undifferentiated pluripotent cells are heavily glycolytic and are not the cell type the disease destroys; the metabolic phenotype is therefore real but is not neuronal. It is a screening platform, and the authors present it as one.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0072593","label":"reactive oxygen species metabolic process","display_label":"reactive oxygen species metabolic process","url":"http://purl.obolibrary.org/obo/GO_0072593"},{"id":"GO:0006754","label":"ATP biosynthetic process","display_label":"ATP biosynthetic process","url":"http://purl.obolibrary.org/obo/GO_0006754"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"NADH/NAD+ ratio","description":null,"target":"Reductive Stress and Bioenergetic Failure","direction":"INCREASED","interpretation":"Reductive stress in a human cell carrying only the NDUFS4 lesion.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:39547516","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39547516","reference_title":"CRISPR-Cas9 mediated knockout of NDUFS4 in human iPSCs: A model for mitochondrial complex I deficiency.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"predominantly associated with an elevated NADH/NAD+ ratio","explanation":"The metabolomic measurement behind this readout."}],"notes":null}],"evidence":[{"reference":"PMID:39547516","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39547516","reference_title":"CRISPR-Cas9 mediated knockout of NDUFS4 in human iPSCs: A model for mitochondrial complex I deficiency.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Human iPSCs were edited using CRISPR-Cas9 to target the NDUFS4 gene, generating isogenic NDUFS4 knockout (KO) cell lines.","explanation":"Establishes the model and its isogenic design."},{"reference":"PMID:39547516","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39547516","reference_title":"CRISPR-Cas9 mediated knockout of NDUFS4 in human iPSCs: A model for mitochondrial complex I deficiency.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"predominantly associated with an elevated NADH/NAD+ ratio","explanation":"The metabolomic measurement behind this readout."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Mitochondrial_Complex_I_Deficiency_Nuclear_Type_1","model_node_id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_1.yaml:NDUFS4 knockout human iPSC line","focus_node_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_1:pathophysiology:Reductive%20Stress%20and%20Bioenergetic%20Failure","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_1.html#pathograph","nodes":[{"id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_1.yaml:NDUFS4 knockout human iPSC line","kind":"experimental_model","kind_label":"NAM model","label":"NDUFS4 knockout human iPSC line","description":"CRISPR-Cas9 knockout of NDUFS4 in human induced pluripotent stem cells, with isogenic controls. Its value is the comparator: patient fibroblast lines differ from controls in their whole genetic background, whereas an isogenic knockout differs at one locus. The limitation the authors state themselves is that undifferentiated iPSCs cannot reproduce the cellular dynamics of the disease, so this is a redox and metabolic platform rather than a model of the encephalopathy.\n`experimental_model_type` is OTHER rather than IPSC_DERIVED_MODEL on purpose. That value is defined as a *differentiated* model derived from induced pluripotent stem cells, and this one is deliberately undifferentiated, which is exactly what the authors' own caveat is about. CELL_LINE does not fit either, being defined for immortalized lines. OTHER is the accurate choice here rather than a placeholder.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_1.html#experimental-model-ndufs4-knockout-human-ipsc-line","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_1:pathophysiology:Reductive%20Stress%20and%20Bioenergetic%20Failure","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reductive Stress and Bioenergetic Failure","description":"Downstream of the enzyme defect, patient-derived cells show partial mitochondrial membrane depolarisation, raised reactive oxygen species and raised NAD(P)H, disturbed cytosolic and mitochondrial calcium and ATP handling, and altered mitochondrial morphology. Pyruvate that cannot be oxidised is converted to lactate, which is what raises lactate in plasma and cerebrospinal fluid.\nA CRISPR knockout of NDUFS4 in human induced pluripotent stem cells reproduces the redox half of this directly, with roughly half the complex I activity of isogenic controls and an elevated NADH/NAD+ ratio - useful because it is a human cell with a defined isogenic comparator rather than a patient line with an uncontrolled background.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_1.html#pathophysiology-reductive-stress-and-bioenergetic-failure","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_1:pathophysiology:Isolated%20Complex%20I%20Deficiency","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Isolated Complex I Deficiency","description":"The enzymatic consequence, and it is isolated in the strict sense: the expression and activity of the other oxidative phosphorylation complexes are not affected. That is what puts this disease in the complex I deficiency nomenclature rather than in the combined respiratory-chain disorders, and it is measurable in the tissues that are biopsied - muscle in 18 of 22 reported patients, fibroblasts in 12.\nIn a patient fibroblast line, complex I activity is severely reduced and, distinctively, insensitive to cAMP stimulation - the NDUFS4 subunit carries the consensus site through which protein kinase A is thought to act on the complex.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_1.html#pathophysiology-isolated-complex-i-deficiency","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_1:phenotype:Lactic%20Acidosis","kind":"phenotype","kind_label":"Phenotype","label":"Lactic Acidosis","description":"Plasma lactate was raised in 16 of 22 patients (73%) and cerebrospinal fluid lactate in 11 of 22 (50%). Both bands are FREQUENT, and the gap between them is a practical point: a normal plasma lactate does not exclude the diagnosis, and CSF lactate adds information. Individual patients with entirely normal blood and CSF lactate have been reported.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_1.html#phenotype-lactic-acidosis","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_1:pathophysiology:Leukocyte-Mediated%20Neuroinflammation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Leukocyte-Mediated Neuroinflammation","description":"Proliferating leukocytes are not just present in the lesions; in the Ndufs4 knockout mouse they are causally required for them. Depleting leukocytes with a CSF1R inhibitor suppressed lesion formation, rescued seizures, respiratory centre function and hyperlactaemia, and substantially extended survival. The same work proposes this as the explanation for why mTOR inhibition works, which had been unexplained for nearly a decade.\nWhether this is true of human NDUFS4 disease is untested. It is recorded because a causal immune step changes what a therapy would target, and because it is the strongest single mechanistic result to come out of this model since the rapamycin finding.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_1.html#pathophysiology-leukocyte-mediated-neuroinflammation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_1:pathophysiology:Secondary%20Hypertrophic%20Cardiomyopathy","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Secondary Hypertrophic Cardiomyopathy","description":"Hypertrophic cardiomyopathy occurs in a minority of NDUFS4 patients - 5 of 22 in the published compilation. Heart- and muscle-specific Ndufs4 knockout mice suggest it is a late, secondary consequence of the complex I defect rather than a primary cardiac lesion, which matters for surveillance: it is something to look for over time rather than at presentation.\nAn iPSC-derived cardiomyocyte model with NDUFS4 deletion reproduces the cardiac phenotype and links it to a specific molecular step - a fall in NAD+/NADH that leaves the cardiac sodium channel NaV1.5 hyperacetylated, producing bradyarrhythmia.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_1.html#pathophysiology-secondary-hypertrophic-cardiomyopathy","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_1:pathophysiology:Symmetric%20Necrotizing%20Brainstem%20and%20Basal%20Ganglia%20Lesions","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Symmetric Necrotizing Brainstem and Basal Ganglia Lesions","description":"The neuropathological endpoint, and the reason most NDUFS4 patients are diagnosed as Leigh syndrome. Brainstem lesions were present in 14 of 22 reported NDUFS4 patients and basal ganglia lesions in 9; cortical atrophy was much less common, in 3. 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Second, the cells are not defenceless: upregulated SLC7A11 imports cystine and raises glutathione, and that response measurably limits the cell death caused by NDUFS7 deficiency.\nConformance note: the module's upstream node - age-related mitochondrial damage and mtDNA mutation - does not apply to a primary nuclear-gene subunit defect, so conformance is declared at this node alone.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_3.html#pathophysiology-isolated-complex-i-deficiency-and-bioenergetic-failure","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_3:pathophysiology:Basal%20Ganglia%20and%20Brainstem%20Vulnerability","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Basal Ganglia and Brainstem Vulnerability","description":"Selective failure of the basal ganglia, midbrain and brainstem, producing the bilateral symmetrical T2-hyperintense lesions that define Leigh syndrome. 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Complete loss of the protein is a more severe perturbation than the biallelic missense variants patients actually carry, and endothelium is not a tissue in which MC1DN2 is known to fail. The model therefore supports the gene-to-bioenergetics step and nothing downstream of it.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[{"id":"CL:0000057","label":"fibroblast","display_label":"Fibroblast","url":"http://purl.obolibrary.org/obo/CL_0000057"}],"biological_processes":[{"id":"GO:0006120","label":"mitochondrial electron transport, NADH to ubiquinone","display_label":"mitochondrial electron transport, NADH to ubiquinone","url":"http://purl.obolibrary.org/obo/GO_0006120"},{"id":"GO:0006119","label":"oxidative phosphorylation","display_label":"oxidative phosphorylation","url":"http://purl.obolibrary.org/obo/GO_0006119"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Complex I activity, oxygen consumption, ATP and membrane potential","description":null,"target":"Impaired NADH-Ubiquinone Oxidoreduction and OXPHOS Deficit","direction":"DECREASED","interpretation":"All four fall together on NDUFS8 loss, which is the expected signature of losing a core subunit of the enzyme.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:38594244","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38594244","reference_title":"The requirement of the mitochondrial protein NDUFS8 for angiogenesis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"resulting in impaired mitochondrial functions in the endothelial cells, causing reduction in mitochondrial oxygen consumption and Complex I activity, decreased ATP production, mitochondrial depolarization, increased oxidative stress and reactive oxygen species (ROS) production, and enhanced lipid oxidation.","explanation":"The full bioenergetic readout panel following NDUFS8 depletion."}],"notes":null}],"evidence":[{"reference":"PMID:38594244","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38594244","reference_title":"The requirement of the mitochondrial protein NDUFS8 for angiogenesis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"NDUFS8 (NADH:ubiquinone oxidoreductase core subunit S8) is a protein that plays a critical role in the function of mitochondrial Complex I.","explanation":"States the gene's role in the complex, which is what makes this model informative for the bioenergetic node."},{"reference":"PMID:38594244","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38594244","reference_title":"The requirement of the mitochondrial protein NDUFS8 for angiogenesis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"resulting in impaired mitochondrial functions in the endothelial cells, causing reduction in mitochondrial oxygen consumption and Complex I activity, decreased ATP production, mitochondrial depolarization, increased oxidative stress and reactive oxygen species (ROS) production, and enhanced lipid oxidation.","explanation":"The full bioenergetic readout panel following NDUFS8 depletion."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Mitochondrial_Complex_I_Deficiency_Nuclear_Type_2","model_node_id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_2.yaml:NDUFS8-silenced and NDUFS8-knockout human endothelial cells","focus_node_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_2:pathophysiology:Impaired%20NADH-Ubiquinone%20Oxidoreduction%20and%20OXPHOS%20Deficit","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_2.html#pathograph","nodes":[{"id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_2.yaml:NDUFS8-silenced and NDUFS8-knockout human endothelial cells","kind":"experimental_model","kind_label":"NAM model","label":"NDUFS8-silenced and NDUFS8-knockout human endothelial cells","description":"Human umbilical vein and other endothelial cells with NDUFS8 silenced by shRNA or deleted by CRISPR/Cas9. This is the only NDUFS8-specific loss-of-function model in the cited literature, and its value here is that it isolates NDUFS8 from the other complex I genes that the patient-fibroblast panels unavoidably pool. It reproduces the bioenergetic lesion cleanly: reduced oxygen consumption and complex I activity, decreased ATP, mitochondrial depolarization, raised ROS and lipid oxidation.\nWhat it also reports - an NDUFS8-dependent ATP-Akt-mTOR-angiogenesis axis, with retinal angiogenesis inhibited in vivo by endothelial-specific knockdown - is deliberately NOT curated as a disease mechanism on this entry. Endothelial cells are not the tissue that fails in MC1DN2, vascular maldevelopment is not a reported patient phenotype, and the paper's own framing is about angiogenesis biology rather than about this disease. The open question is recorded as a HUMAN_MODEL_MISMATCH discussion instead.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_2.html#experimental-model-ndufs8-silenced-and-ndufs8-knockout-human-endothelial-cells","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_2:pathophysiology:Impaired%20NADH-Ubiquinone%20Oxidoreduction%20and%20OXPHOS%20Deficit","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired NADH-Ubiquinone Oxidoreduction and OXPHOS Deficit","description":"Reduced NADH oxidation and electron delivery to ubiquinone lower proton pumping and oxidative phosphorylation capacity. Two consequences follow that are visible in patient cells: the mitochondrial membrane potential falls, and NADH that cannot be reoxidized through the respiratory chain accumulates - which is why exogenous NAD+ and pyruvate, both of which restore cytosolic NAD+ regeneration, rescue these cells.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_2.html#pathophysiology-impaired-nadh-ubiquinone-oxidoreduction-and-oxphos-deficit","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_2:pathophysiology:Glycolytic%20Compensation%20Masking%20the%20Bioenergetic%20Deficit","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Glycolytic Compensation Masking the Bioenergetic Deficit","description":"A compensatory response that is also a methodological trap, and the reason it is curated as a node rather than left as a footnote. Cells with complex I deficiency upregulate glycolysis to replace lost mitochondrial ATP, and that adaptation masks other consequences of the deficiency. Replacing glucose with galactose in a pyruvate-free medium removes the glycolytic escape route: under those conditions patient fibroblasts die while control cells do not.\nClinically the same logic explains why these patients decompensate under catabolic stress, and why a resting biochemical measurement can understate how close to the edge a tissue is.\nGlycolysis is not the only compensatory response in play. In the late-onset patient's skeletal muscle the mitochondrially encoded complex IV COI subunit was ELEVATED while complex I protein was reduced, which the reporting authors read as an attempt to compensate by inducing mitochondrial gene expression. That is hedged as a reading rather than a demonstration, but it is worth recording: an assay that finds one respiratory complex up and another down should not be assumed to have gone wrong.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_2.html#pathophysiology-glycolytic-compensation-masking-the-bioenergetic-deficit","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_2:pathophysiology:Increased%20Reactive%20Oxygen%20Species%20Production","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Increased Reactive Oxygen Species Production","description":"Fibroblasts from children with nuclear complex I gene defects, including NDUFS8, show raised reactive oxygen species. The interesting finding is not the ROS itself but what happens when it is removed: chronic treatment with the water-soluble vitamin E derivative Trolox dramatically lowers ROS and is accompanied by a substantial increase in the amount of complex I. The reporting authors read that as evidence that complex I expression is itself regulated by ROS, which makes this node a feedback modifier on the assembly node rather than a terminal consequence.\nIt is curated PROVISIONAL because the causal claim rests on the correlated response to one intervention in cultured fibroblasts, and because the authors describe the contribution of ROS to pathogenesis as supported by circumstantial evidence.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_2.html#pathophysiology-increased-reactive-oxygen-species-production","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_2:pathophysiology:Leigh%20Syndrome%20and%20Mitochondrial%20Encephalomyopathy","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Leigh Syndrome and Mitochondrial Encephalomyopathy","description":"The clinical endpoint, and the striking thing about it in this entity is its range rather than its severity. The index patient had neuropathologically proven Leigh syndrome with a progressive course ending in death in the first months of life - the presentation a core-subunit defect predicts. But a second patient had late-onset disease with only a partial complex I defect, and three siblings from a consanguineous family presented as \"progressive external ophthalmoplegia plus\", a picture in which nobody would have thought to sequence this gene. The authors of that report make the methodological point explicitly: untargeted exome analysis can re-write a phenotype.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_2.html#pathophysiology-leigh-syndrome-and-mitochondrial-encephalomyopathy","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_2:pathophysiology:Reduced%20Complex%20I%20Amount%20and%20Intrinsic%20Catalytic%20Activity","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced Complex I Amount and Intrinsic Catalytic Activity","description":"The step at which this entity's biochemistry says something the assembly story alone does not. In control fibroblasts the ratio between complex I enzymatic activity and complex I amount is exactly one - enzyme present is enzyme working. In fibroblasts from children with nuclear complex I gene defects including NDUFS8 that ratio falls below one. The enzyme that does get assembled is therefore intrinsically impaired, not merely scarce.\nThat is what a core subunit carrying the terminal iron-sulfur cluster would be expected to do, and it distinguishes this entity mechanistically from the accessory-subunit deficiencies elsewhere in the nuclear complex I series, where the lesion is essentially one of quantity. Practically, it also predicts a ceiling on any therapy that works by increasing the amount of complex I - see the antioxidant node.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_2.html#pathophysiology-reduced-complex-i-amount-and-intrinsic-catalytic-activity","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"}],"edges":[{"id":"model-link:0:model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_2.yaml:NDUFS8-silenced and NDUFS8-knockout human endothelial cells","source_id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_2.yaml:NDUFS8-silenced and NDUFS8-knockout human endothelial cells","target_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_2:pathophysiology:Impaired%20NADH-Ubiquinone%20Oxidoreduction%20and%20OXPHOS%20Deficit","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"Gene-specific depletion of NDUFS8 alone reproduces the bioenergetic lesion - falling complex I activity, oxygen consumption, ATP and membrane potential - without any confound from other complex I genes.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_2:3:0","source_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_2:pathophysiology:Impaired%20NADH-Ubiquinone%20Oxidoreduction%20and%20OXPHOS%20Deficit","target_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_2:pathophysiology:Glycolytic%20Compensation%20Masking%20the%20Bioenergetic%20Deficit","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[3].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Cells respond to falling mitochondrial ATP production by upregulating glycolysis.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_2:3:1","source_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_2:pathophysiology:Impaired%20NADH-Ubiquinone%20Oxidoreduction%20and%20OXPHOS%20Deficit","target_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_2:pathophysiology:Increased%20Reactive%20Oxygen%20Species%20Production","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[3].downstream[1]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"A partially blocked, over-reduced electron transport chain leaks electrons to oxygen.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_2:3:2","source_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_2:pathophysiology:Impaired%20NADH-Ubiquinone%20Oxidoreduction%20and%20OXPHOS%20Deficit","target_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_2:pathophysiology:Leigh%20Syndrome%20and%20Mitochondrial%20Encephalomyopathy","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[3].downstream[2]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Neurons and muscle are the tissues least able to tolerate reduced oxidative phosphorylation capacity.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_2:2:0","source_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_2:pathophysiology:Reduced%20Complex%20I%20Amount%20and%20Intrinsic%20Catalytic%20Activity","target_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_2:pathophysiology:Impaired%20NADH-Ubiquinone%20Oxidoreduction%20and%20OXPHOS%20Deficit","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Less enzyme, working less well, oxidizes less NADH and delivers fewer electrons to ubiquinone.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0}]}},{"target":"Increased Reactive Oxygen Species Production","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_2.html#pathophysiology-increased-reactive-oxygen-species-production","relationship":"RECAPITULATES","relationship_label":"Recapitulates","fidelity":"MODERATE","fidelity_label":"Moderate","description":"NDUFS8 depletion raises oxidative stress, ROS and lipid oxidation, which corroborates in a gene-specific model the raised ROS seen in the pooled patient-fibroblast panels.","limitations":"Gene knockout rather than patient missense allele, and endothelium rather than neurons or muscle. It confirms that ROS follows NDUFS8 loss; it says nothing about the proposed feedback of ROS onto complex I amount, which remains supported only by the Trolox experiment.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[{"id":"CL:0000057","label":"fibroblast","display_label":"Fibroblast","url":"http://purl.obolibrary.org/obo/CL_0000057"}],"biological_processes":[{"id":"GO:0072593","label":"reactive oxygen species metabolic process","display_label":"reactive oxygen species metabolic process","url":"http://purl.obolibrary.org/obo/GO_0072593"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Reactive oxygen species and lipid oxidation","description":null,"target":"Increased Reactive Oxygen Species Production","direction":"INCREASED","interpretation":"Raised ROS is a direct consequence of losing this subunit, in a system with no other complex I gene defect.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:38594244","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38594244","reference_title":"The requirement of the mitochondrial protein NDUFS8 for angiogenesis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"increased oxidative stress and reactive oxygen species (ROS) production, and enhanced lipid oxidation","explanation":"The oxidative-stress readout in NDUFS8-depleted cells."}],"notes":null}],"evidence":[{"reference":"PMID:38594244","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38594244","reference_title":"The requirement of the mitochondrial protein NDUFS8 for angiogenesis.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"ATP reduction, oxidative stress, and enhanced lipid oxidation were detected in mouse retinal tissues with endothelial knockdown of NDUFS8.","explanation":"Confirms the same oxidative signature in vivo, though in mouse retina."},{"reference":"PMID:38594244","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38594244","reference_title":"The requirement of the mitochondrial protein NDUFS8 for angiogenesis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"increased oxidative stress and reactive oxygen species (ROS) production, and enhanced lipid oxidation","explanation":"The oxidative-stress readout in NDUFS8-depleted cells."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Mitochondrial_Complex_I_Deficiency_Nuclear_Type_2","model_node_id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_2.yaml:NDUFS8-silenced and NDUFS8-knockout human endothelial cells","focus_node_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_2:pathophysiology:Increased%20Reactive%20Oxygen%20Species%20Production","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_2.html#pathograph","nodes":[{"id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_2.yaml:NDUFS8-silenced and NDUFS8-knockout human endothelial cells","kind":"experimental_model","kind_label":"NAM model","label":"NDUFS8-silenced and NDUFS8-knockout human endothelial cells","description":"Human umbilical vein and other endothelial cells with NDUFS8 silenced by shRNA or deleted by CRISPR/Cas9. 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The open question is recorded as a HUMAN_MODEL_MISMATCH discussion instead.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_2.html#experimental-model-ndufs8-silenced-and-ndufs8-knockout-human-endothelial-cells","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_2:pathophysiology:Increased%20Reactive%20Oxygen%20Species%20Production","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Increased Reactive Oxygen Species Production","description":"Fibroblasts from children with nuclear complex I gene defects, including NDUFS8, show raised reactive oxygen species. 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The reporting authors read that as evidence that complex I expression is itself regulated by ROS, which makes this node a feedback modifier on the assembly node rather than a terminal consequence.\nIt is curated PROVISIONAL because the causal claim rests on the correlated response to one intervention in cultured fibroblasts, and because the authors describe the contribution of ROS to pathogenesis as supported by circumstantial evidence.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_2.html#pathophysiology-increased-reactive-oxygen-species-production","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_2:pathophysiology:Complex%20I%20Assembly%20and%20Stability%20Failure","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Complex I Assembly and Stability Failure","description":"Western blotting of patient material shows not only a deficiency of the NDUFS8 polypeptide itself - which a mutation in its own gene would produce trivially - but reductions in other nuclear-encoded subunits of complex I as well. That second observation is the informative one: the rest of the complex cannot be maintained without TYKY, so the subunit is required for assembly, for stability of the assembled enzyme, or for both. The available data do not distinguish those alternatives, and the reporting authors do not claim to.\nThere is a structural proposal for what the subunit is doing. NDUFS8/TYKY is thought to connect the membrane and peripheral domains of complex I - the boundary between the arm embedded in the inner membrane and the arm that carries the electron relay. A subunit at that junction is exactly the kind whose loss would destabilise the whole assembly rather than remove one catalytic step. Consistent with that, the late-onset patient also showed a drastic reduction in the 39-kDa subunit, which is proposed to sit at the same domain boundary and may interact with TYKY directly.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_2.html#pathophysiology-complex-i-assembly-and-stability-failure","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_2:pathophysiology:Impaired%20NADH-Ubiquinone%20Oxidoreduction%20and%20OXPHOS%20Deficit","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired NADH-Ubiquinone Oxidoreduction and OXPHOS Deficit","description":"Reduced NADH oxidation and electron delivery to ubiquinone lower proton pumping and oxidative phosphorylation capacity. 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depletion."},{"reference":"PMID:38594244","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38594244","reference_title":"The requirement of the mitochondrial protein NDUFS8 for angiogenesis.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"ATP reduction, oxidative stress, and enhanced lipid oxidation were detected in mouse retinal tissues with endothelial knockdown of NDUFS8.","explanation":"Confirms the same oxidative signature in vivo, though in mouse retina."},{"reference":"PMID:38594244","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38594244","reference_title":"The requirement of the mitochondrial protein NDUFS8 for angiogenesis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"increased oxidative stress and reactive oxygen species (ROS) production, and enhanced lipid oxidation","explanation":"The oxidative-stress readout in NDUFS8-depleted cells."}],"evidence_text":["NDUFS8 (NADH:ubiquinone oxidoreductase core subunit S8) is a protein that 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Neonatal rat cardiomyocytes are exposed to doxorubicin with ABCB8 knockdown or overexpression. Compartmental iron, cellular oxidant probes, viability and TUNEL are assessed. 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Signaling is genotype-divergent: MDP-stimulated NF-kappaB activity and TNF secretion are suppressed in the IVS8+158/R702W haplotype, so the disease cannot be reduced to uniform NOD2 gain of function.","url":"https://dismech.monarchinitiative.org/pages/disorders/Yao_Syndrome.html#pathophysiology-aberrant-nod2-pathway-activation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3AYao_Syndrome:pathophysiology:Dysregulated%20Proinflammatory%20Cytokine%20Production","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Dysregulated Proinflammatory Cytokine Production","description":"Aberrant NOD2 signaling drives excess proinflammatory cytokine production, most prominently IL-6, with contributions from IL-1beta and TNF. Basal and MDP-enhanced IL-6 secretion is elevated in IVS8+158 carriers, providing the rationale for IL-6 and IL-1 blockade. Resting plasma cytokine levels can be normal, so the dysregulation is most evident on cellular stimulation rather than as a persistent systemic elevation.","url":"https://dismech.monarchinitiative.org/pages/disorders/Yao_Syndrome.html#pathophysiology-dysregulated-proinflammatory-cytokine-production","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3AYao_Syndrome:pathophysiology:NOD2%20Low-Penetrance%20Susceptibility%20Variants","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"NOD2 Low-Penetrance Susceptibility Variants","description":"Germline low-frequency, low-penetrance NOD2 variants - chiefly the deep-intronic IVS8+158 and the missense R702W, alone or co-inherited, with additional L1007fs and V955I - are the genetic substrate of YAOS. They are modeled as susceptibility rather than deterministic alleles because they are common in the general population and most carriers never develop disease. YAOS-associated coding variants cluster in and around the central nucleotide-binding domain, distinct from the LRR-region variants that predispose to Crohn disease.","url":"https://dismech.monarchinitiative.org/pages/disorders/Yao_Syndrome.html#pathophysiology-nod2-low-penetrance-susceptibility-variants","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"}],"edges":[{"id":"model-link:0:model:kb/disorders/Yao_Syndrome.yaml:NOD2 Q902K reporter transfection in HEK293T cells","source_id":"model:kb/disorders/Yao_Syndrome.yaml:NOD2 Q902K reporter transfection in HEK293T 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A cardiovascular-mutant medaka carrying a missense change in an Ig domain at the M-line-A-band transition zone of titin shows diastolic dysfunction and hypertrophic myocardium; homozygotes have fewer myofibrils, disrupted sarcomeres and stiffer titin isoforms, while heterozygotes show M-line disassembly resembling the human pathology. Positional cloning of that mutation is what directed the screen of 96 sarcomere-negative familial HCM patients in which the two human Ig-domain alleles curated here were found.","notes":null,"context_id":"disorder:Hypertrophic_Cardiomyopathy_9","context_kind":"Disorder","disease_name":"Hypertrophic Cardiomyopathy 9","disease_synonyms":["CMH9","TTN hypertrophic cardiomyopathy","cardiomyopathy, familial hypertrophic, 9","hypertrophic cardiomyopathy type 9","hypertrophic cardiomyopathy caused by mutation in TTN"],"disease_term":{"id":"MONDO:0013412","label":"hypertrophic cardiomyopathy 9","display_label":"hypertrophic cardiomyopathy 9","url":"http://purl.obolibrary.org/obo/MONDO_0013412"},"experimental_model_type":"OTHER","experimental_model_type_label":"Other","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":{"id":"NCBITaxon:8090","label":"Oryzias latipes","display_label":"Japanese medaka","url":"http://purl.obolibrary.org/obo/NCBITaxon_8090"},"organism_label":"Oryzias latipes","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[{"id":"CL:0000746","label":"cardiac muscle cell","display_label":"Cardiomyocyte","url":"http://purl.obolibrary.org/obo/CL_0000746"}],"linked_cell_type_labels":["cardiac muscle cell"],"cell_types":[{"id":"CL:0000746","label":"cardiac muscle cell","display_label":"Cardiomyocyte","url":"http://purl.obolibrary.org/obo/CL_0000746"}],"cell_type_labels":["cardiac muscle cell"],"conditions":[],"cell_source":null,"source_category":null,"culture_system":null,"publication":"PMID:31628103","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/31628103","mechanisms":[{"target":"Perturbed Titin-MURF1 Interaction and Enhanced Titin Degradation","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_9.html#pathophysiology-perturbed-titin-murf1-interaction-and-enhanced-titin-degradation","relationship":"PARTIALLY_RECAPITULATES","relationship_label":"Partially Recapitulates","fidelity":"LOW","fidelity_label":"Low","description":"Reproduces a hypertrophic, diastolically impaired myocardium from a titin Ig-domain missense change, which is the mechanism this node proposes.","limitations":"Fidelity is LOW and deliberately so. 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The model motivates the hypothesis; it does not establish the human mechanism, which is why every node in this entry remains HYPOTHETICAL.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[{"id":"CL:0000746","label":"cardiac muscle cell","display_label":"Cardiomyocyte","url":"http://purl.obolibrary.org/obo/CL_0000746"}],"biological_processes":[{"id":"GO:0016567","label":"protein ubiquitination","display_label":"Protein ubiquitination","url":"http://purl.obolibrary.org/obo/GO_0016567"},{"id":"GO:0030239","label":"myofibril assembly","display_label":"Myofibril assembly","url":"http://purl.obolibrary.org/obo/GO_0030239"}],"pathways":[],"genes":[{"id":"hgnc:12403","label":"TTN","display_label":"TTN","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/12403"}],"chemicals":[],"readouts":[],"evidence":[{"reference":"PMID:31628103","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/31628103","reference_title":"Perturbation of the titin/MURF1 signaling complex is associated with hypertrophic cardiomyopathy in a fish model and in human patients.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"The nsh homozygotes had fewer myofibrils, disrupted sarcomeres and expressed pathologically stiffer titin isoforms.","explanation":"The structural phenotype of the model, and the observation that ties a titin Ig-domain lesion to sarcomeric disruption."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Hypertrophic_Cardiomyopathy_9","model_node_id":"model:kb/disorders/Hypertrophic_Cardiomyopathy_9.yaml:non-spring heart (nsh) medaka fish titin Ig-domain mutant","focus_node_id":"node:disorder%3AHypertrophic_Cardiomyopathy_9:pathophysiology:Perturbed%20Titin-MURF1%20Interaction%20and%20Enhanced%20Titin%20Degradation","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_9.html#pathograph","nodes":[{"id":"model:kb/disorders/Hypertrophic_Cardiomyopathy_9.yaml:non-spring heart (nsh) medaka fish titin Ig-domain mutant","kind":"experimental_model","kind_label":"NAM model","label":"non-spring heart (nsh) medaka fish titin Ig-domain mutant","description":"The primary experimental support for the titin/MURF1 hypothesis, and the only whole-organism model in this entry. 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Positional cloning of that mutation is what directed the screen of 96 sarcomere-negative familial HCM patients in which the two human Ig-domain alleles curated here were found.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_9.html#experimental-model-non-spring-heart-nsh-medaka-fish-titin-ig-domain-mutant","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_9:pathophysiology:Perturbed%20Titin-MURF1%20Interaction%20and%20Enhanced%20Titin%20Degradation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Perturbed Titin-MURF1 Interaction and Enhanced Titin Degradation","description":"Missense substitutions in titin immunoglobulin domains near the M-line increase titin binding to muscle-specific RING finger protein 1 (MURF1), an E3 ubiquitin ligase, and enhance ubiquitin-mediated titin degradation. In the medaka model this was accompanied by fewer myofibrils, disrupted sarcomeres, pathologically stiff titin isoforms, and M-line disassembly. Human support is limited to two variants found in a 96-patient sarcomere-negative familial HCM screen plus in vitro assays.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_9.html#pathophysiology-perturbed-titin-murf1-interaction-and-enhanced-titin-degradation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"HYPOTHETICAL","mechanism_confidence_label":"Hypothetical"},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_9:pathophysiology:Hypertrophic%20Remodeling%20of%20the%20Left%20Ventricle","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Hypertrophic Remodeling of the Left Ventricle","description":"The shared clinical endpoint of all hypertrophic cardiomyopathy: left ventricular wall thickening with myocyte disarray and impaired diastolic filling. This node is well established as the phenotype of HCM in general; it is tagged HYPOTHETICAL here only in the sense that its attribution to a TTN variant in this entity is unproven. The conserved downstream remodeling chain is modelled generically in the kb/modules/ cardiomyopathy_maladaptive_remodeling module; no conforms_to link is declared from this entry because the disease-specific causal edges into this node are themselves hypothetical.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_9.html#pathophysiology-hypertrophic-remodeling-of-the-left-ventricle","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":"HYPOTHETICAL","mechanism_confidence_label":"Hypothetical"},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_9:pathophysiology:Rare%20TTN%20Variants%20in%20Sarcomere-Negative%20Hypertrophic%20Cardiomyopathy","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Rare TTN Variants in Sarcomere-Negative Hypertrophic Cardiomyopathy","description":"The proximal node of the claimed CMH9 mechanism: a rare heterozygous TTN variant in a patient with hypertrophic cardiomyopathy who has no variant in an established sarcomere gene. Both reported series ascertained patients this way — by residual, gene-elusive HCM — which is a candidate-gene design that cannot by itself establish causality. Titin is the largest human protein and carries a high background burden of rare variation, so rare TTN variants are expected in any sufficiently large cohort. This node is tagged HYPOTHETICAL because its causal link to the downstream hypertrophic phenotype is exactly what remains unproven.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_9.html#pathophysiology-rare-ttn-variants-in-sarcomere-negative-hypertrophic-cardiomyopathy","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"HYPOTHETICAL","mechanism_confidence_label":"Hypothetical"}],"edges":[{"id":"model-link:0:model:kb/disorders/Hypertrophic_Cardiomyopathy_9.yaml:non-spring heart (nsh) medaka fish titin Ig-domain mutant","source_id":"model:kb/disorders/Hypertrophic_Cardiomyopathy_9.yaml:non-spring heart (nsh) medaka fish titin Ig-domain mutant","target_id":"node:disorder%3AHypertrophic_Cardiomyopathy_9:pathophysiology:Perturbed%20Titin-MURF1%20Interaction%20and%20Enhanced%20Titin%20Degradation","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Partially Recapitulates","directed":false,"relationship":"PARTIALLY_RECAPITULATES","fidelity":"LOW","causal_link_type":null,"causal_link_type_label":null,"description":"Reproduces a hypertrophic, diastolically impaired myocardium from a titin Ig-domain missense change, which is the mechanism this node proposes.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AHypertrophic_Cardiomyopathy_9:2:0","source_id":"node:disorder%3AHypertrophic_Cardiomyopathy_9:pathophysiology:Perturbed%20Titin-MURF1%20Interaction%20and%20Enhanced%20Titin%20Degradation","target_id":"node:disorder%3AHypertrophic_Cardiomyopathy_9:pathophysiology:Hypertrophic%20Remodeling%20of%20the%20Left%20Ventricle","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[0]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"Demonstrated in a fish model; 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cardiomyocyte hypertrophic remodeling yields clinical hypertrophic cardiomyopathy.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ANoonan_Syndrome:6:2","source_id":"node:disorder%3ANoonan_Syndrome:pathophysiology:ERK%20Cascade%20Hyperactivation","target_id":"node:disorder%3ANoonan_Syndrome:pathophysiology:Cardiomyocyte%20Hypertrophy","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[6].downstream[2]","label":"Causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":null,"causal_link_type_label":null,"description":"Sustained ERK signaling promotes hypertrophic growth and fetal gene reprogramming.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ANoonan_Syndrome:2:1","source_id":"node:disorder%3ANoonan_Syndrome:pathophysiology:RAF1%20Kinase%20Hyperactivation","target_id":"node:disorder%3ANoonan_Syndrome:pathophysiology:Cardiomyocyte%20Hypertrophy","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[1]","label":"Causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":null,"causal_link_type_label":null,"description":"RAF1 kinase hyperactivation is strongly associated with hypertrophic cardiomyopathy development.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ANoonan_Syndrome:3:1","source_id":"node:disorder%3ANoonan_Syndrome:pathophysiology:RIT1-Mediated%20RAF%20Recruitment","target_id":"node:disorder%3ANoonan_Syndrome:pathophysiology:Cardiomyocyte%20Hypertrophy","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[3].downstream[1]","label":"Causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":null,"causal_link_type_label":null,"description":"RIT1 mutations are strongly associated with hypertrophic cardiomyopathy.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1}]}},{"target":"ERK Cascade Hyperactivation","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Noonan_Syndrome.html#pathophysiology-erk-cascade-hyperactivation","relationship":"PERTURBS","relationship_label":"Perturbs","fidelity":"MODERATE","fidelity_label":"Moderate","description":"Pharmacological and genetic perturbation of MEK1/2, ERK1/2, and ERK5 in RAF1 S257L/+ iPSC-cardiomyocytes dissects which arm of RAS-MAPK signaling drives which part of the hypertrophic phenotype.","limitations":null,"biological_scale":null,"anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0000165","label":"MAPK cascade","display_label":"MAPK cascade","url":"http://purl.obolibrary.org/obo/GO_0000165"},{"id":"GO:0070372","label":"regulation of ERK1 and ERK2 cascade","display_label":"regulation of ERK1 and ERK2 cascade","url":"http://purl.obolibrary.org/obo/GO_0070372"}],"pathways":[],"genes":[{"id":"hgnc:6871","label":"MAPK1","display_label":"MAPK1","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/6871"}],"chemicals":[],"readouts":[{"name":"Cardiomyocyte hypertrophy after MEK1/2-ERK1/2 inhibition","description":"Cell surface area of RAF1S257L/+ iPSC-cardiomyocytes treated with the MEK1/2 inhibitors PD98059 or Trametinib, which strongly reduce ERK1/2 phosphorylation.","target":"ERK Cascade Hyperactivation","direction":"UNCHANGED","interpretation":"MEK1/2-ERK1/2 inhibition abolishes ERK1/2 activation without reducing cell size, so this model refutes ERK1/2 signaling specifically as the driver of the hypertrophy this entry's ERK Cascade Hyperactivation to Cardiomyocyte Hypertrophy edge asserts. The paper instead attributes the enlarged-cell phenotype to ERK5, a MAPK pathway this entry does not otherwise model.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:31163979","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/31163979","reference_title":"Inducible Pluripotent Stem Cell-Derived Cardiomyocytes Reveal Aberrant Extracellular Regulated Kinase 5 and Mitogen-Activated Protein Kinase Kinase 1/2 Signaling Concomitantly Promote Hypertrophic Cardiomyopathy in RAF1-Associated Noonan Syndrome.","supports":"REFUTE","evidence_source":"IN_VITRO","snippet":"Importantly, although ERK1/2 activation was strongly reduced, there was no significant effect on hypertrophy in RAF1S257L/+ iCMs in response to treatment with either PD98059 or Trametinib (Fig.4C–D), suggesting that MEK1/2-ERK1/2 activation is not the principal driver of hypertrophy in NS-associated RAF1 mutations.","explanation":"Directly reports the negative result for ERK1/2 as the hypertrophy driver."},{"reference":"PMID:31163979","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/31163979","reference_title":"Inducible Pluripotent Stem Cell-Derived Cardiomyocytes Reveal Aberrant Extracellular Regulated Kinase 5 and Mitogen-Activated Protein Kinase Kinase 1/2 Signaling Concomitantly Promote Hypertrophic Cardiomyopathy in RAF1-Associated Noonan Syndrome.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"the enlarged cardiomyocyte phenotype is a direct consequence of increased extracellular regulated kinase 5 (ERK5) signaling, a pathway not previously known to be involved in NS.","explanation":"Reports the alternative driver the paper identifies for the hypertrophic phenotype."}],"notes":null}],"evidence":[{"reference":"PMID:31163979","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/31163979","reference_title":"Inducible Pluripotent Stem Cell-Derived Cardiomyocytes Reveal Aberrant Extracellular Regulated Kinase 5 and Mitogen-Activated Protein Kinase Kinase 1/2 Signaling Concomitantly Promote Hypertrophic Cardiomyopathy in RAF1-Associated Noonan Syndrome.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"METHODS: We used patient-derived RAF1S257L/+ and CRISPR-Cas9-generated isogenic control inducible pluripotent stem cell (iPSC)-derived cardiomyocytes to model NS RAF1-associated HCM and to further delineate the molecular mechanisms underlying the disease.","explanation":"Establishes the model as informative for dissecting which arm of the ERK cascade node drives which part of the phenotype."},{"reference":"PMID:31163979","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/31163979","reference_title":"Inducible Pluripotent Stem Cell-Derived Cardiomyocytes Reveal Aberrant Extracellular Regulated Kinase 5 and Mitogen-Activated Protein Kinase Kinase 1/2 Signaling Concomitantly Promote Hypertrophic Cardiomyopathy in RAF1-Associated Noonan Syndrome.","supports":"REFUTE","evidence_source":"IN_VITRO","snippet":"Importantly, although ERK1/2 activation was strongly reduced, there was no significant effect on hypertrophy in RAF1S257L/+ iCMs in response to treatment with either PD98059 or Trametinib (Fig.4C–D), suggesting that MEK1/2-ERK1/2 activation is not the principal driver of hypertrophy in NS-associated RAF1 mutations.","explanation":"Directly reports the negative result for ERK1/2 as the hypertrophy driver."},{"reference":"PMID:31163979","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/31163979","reference_title":"Inducible Pluripotent Stem Cell-Derived Cardiomyocytes Reveal Aberrant Extracellular Regulated Kinase 5 and Mitogen-Activated Protein Kinase Kinase 1/2 Signaling Concomitantly Promote Hypertrophic Cardiomyopathy in RAF1-Associated Noonan Syndrome.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"the enlarged cardiomyocyte phenotype is a direct consequence of increased extracellular regulated kinase 5 (ERK5) signaling, a pathway not previously known to be involved in NS.","explanation":"Reports the alternative driver the paper identifies for the hypertrophic phenotype."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Noonan_Syndrome","model_node_id":"model:kb/disorders/Noonan_Syndrome.yaml:Noonan syndrome iPSC-cardiomyocyte model","focus_node_id":"node:disorder%3ANoonan_Syndrome:pathophysiology:ERK%20Cascade%20Hyperactivation","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Noonan_Syndrome.html#pathograph","nodes":[{"id":"model:kb/disorders/Noonan_Syndrome.yaml:Noonan syndrome iPSC-cardiomyocyte model","kind":"experimental_model","kind_label":"NAM model","label":"Noonan syndrome iPSC-cardiomyocyte model","description":"Patient-derived Noonan syndrome induced pluripotent stem cell cardiomyocytes modeling childhood-onset cardiomyopathy and RAF1/PTPN11-driven transcriptional 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This affects cell proliferation, differentiation, and survival during embryonic development and postnatal life. MAPK1 is bound here rather than on an upstream node because it encodes ERK2 itself: the NS13 genotype alters the effector this node names instead of altering an input to it.","url":"https://dismech.monarchinitiative.org/pages/disorders/Noonan_Syndrome.html#pathophysiology-erk-cascade-hyperactivation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ANoonan_Syndrome:pathophysiology:Additional%20RAS-MAPK%20Signal-Amplifying%20Variants","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Additional RAS-MAPK Signal-Amplifying Variants","description":"Additional established Noonan genes affecting small GTPases, RAF/MEK kinases, and RasGAP regulation converge on increased RAS-MAPK pathway throughput despite diverse molecular entry points. Two of the genes bound here reach that endpoint by losing a brake rather than by gaining a signal: CBL is an E3 ubiquitin ligase whose mutations impair receptor ubiquitylation, and SPRED2 is a negative modulator of EGF-promoted RAF1, MEK and ERK phosphorylation. SPRED2 is the exception to this entry's dominant pattern - it acts recessively - and is recorded in the autosomal recessive inheritance block alongside LZTR1.","url":"https://dismech.monarchinitiative.org/pages/disorders/Noonan_Syndrome.html#pathophysiology-additional-ras-mapk-signal-amplifying-variants","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ANoonan_Syndrome:pathophysiology:Cardiac%20Valve%20Morphogenesis%20Defects","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Cardiac Valve Morphogenesis Defects","description":"In endocardial and valvular tissues, perturbed ERK signaling alters endocardial-mesenchymal transition and valve morphogenesis, underlying pulmonary valve stenosis, the most common cardiac defect in Noonan 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finding.","url":"https://dismech.monarchinitiative.org/pages/disorders/Noonan_Syndrome.html#phenotype-cryptorchidism","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ANoonan_Syndrome:phenotype:Downslanted%20Palpebral%20Fissures","kind":"phenotype","kind_label":"Phenotype","label":"Downslanted Palpebral Fissures","description":"Downward slanting of the eye openings is a common facial 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surveillance.","url":"https://dismech.monarchinitiative.org/pages/disorders/Noonan_Syndrome.html#phenotype-hearing-loss","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ANoonan_Syndrome:phenotype:High%20Palate","kind":"phenotype","kind_label":"Phenotype","label":"High Palate","description":"A high-arched palate is part of the craniofacial phenotype spectrum of Noonan 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hypogonadism.","url":"https://dismech.monarchinitiative.org/pages/disorders/Noonan_Syndrome.html#phenotype-hypogonadotropic-hypogonadism","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ANoonan_Syndrome:phenotype:Low-set%20Ears","kind":"phenotype","kind_label":"Phenotype","label":"Low-set Ears","description":"Posteriorly rotated, low-set ears are characteristic.","url":"https://dismech.monarchinitiative.org/pages/disorders/Noonan_Syndrome.html#phenotype-low-set-ears","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ANoonan_Syndrome:pathophysiology:Lymphatic%20Structural%20Abnormalities","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Lymphatic Structural Abnormalities","description":"Noonan syndrome can include severe central and peripheral lymphatic abnormalities that produce clinically significant fluid and lymphatic-flow complications.","url":"https://dismech.monarchinitiative.org/pages/disorders/Noonan_Syndrome.html#pathophysiology-lymphatic-structural-abnormalities","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ANoonan_Syndrome:pathophysiology:LZTR1-Mediated%20RAS%20Proteostasis%20Defect","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"LZTR1-Mediated RAS Proteostasis Defect","description":"Loss of LZTR1-mediated RAS proteostasis through CRL3 E3 ligase increases RAS-family protein levels (including MRAS, RIT1, and KRAS) and MAPK signaling. Dominant LZTR1 mutations act in a dominant-negative manner to disrupt ubiquitination and degradation of RAS proteins.","url":"https://dismech.monarchinitiative.org/pages/disorders/Noonan_Syndrome.html#pathophysiology-lztr1-mediated-ras-proteostasis-defect","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ANoonan_Syndrome:pathophysiology:Neural%20Crest%20Cell%20Developmental%20Dysregulation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Neural Crest Cell Developmental Dysregulation","description":"The neural crest is the lineage in which the RAS-MAPK lesion reaches the conotruncal and craniofacial features of Noonan syndrome. Neural crest cells populate the cardiac outflow tract and supply a large share of the facial and cranial skeleton, and SHP2 is separately required within them: ablating PTPN11 in premigratory neural crest blocks outflow-tract colonisation and produces persistent truncus arteriosus with pronounced craniofacial deficits, while driving the Noonan SHP2 Q79R allele in neural crest is by itself enough to cause craniofacial malformation. Modelling this as an explicit node makes the neural crest step visible instead of leaving the craniofacial and conotruncal outcomes hanging directly off the ERK node.\nThe `modifier` on neural crest cell migration is deliberately DYSREGULATED rather than INCREASED or DECREASED: the direction is not fixed across lesions. Loss of SHP2 in neural crest impairs migration into the outflow tract, whereas at least one Noonan-spectrum missense variant has been reported to drive excessive migration. 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MEK1/2-ERK1/2 inhibition"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[{"statement":"Noonan iPSC-cardiomyocytes capture cardiomyopathy-linked cell-cycle and signaling defects in a genotype-resolved human cardiac model","evidence":[{"reference":"PMID:34988410","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/34988410","reference_title":"Cell cycle defects underlie childhood-onset cardiomyopathy associated with Noonan syndrome.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Here, through analysis of sarcomeric myosin conformational states, histopathology, and gene expression in left ventricular myocardial tissue from NS-CM, HCM, and normal hearts complemented with disease modeling in cardiomyocytes differentiated from patient-derived PTPN11 N308S/+ induced pluripotent stem cells, we demonstrate distinct disease phenotypes between NS-CM and HCM and uncover cell cycle defects as a potential driver of NS-CM.","explanation":"Supports patient-derived iPSC-cardiomyocytes as a disease-relevant Noonan cardiomyopathy model."},{"reference":"PMID:31163979","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/31163979","reference_title":"Inducible Pluripotent Stem Cell-Derived Cardiomyocytes Reveal Aberrant Extracellular Regulated Kinase 5 and Mitogen-Activated Protein Kinase Kinase 1/2 Signaling Concomitantly Promote Hypertrophic Cardiomyopathy in RAF1-Associated Noonan Syndrome.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"METHODS: We used patient-derived RAF1S257L/+ and CRISPR-Cas9-generated isogenic control inducible pluripotent stem cell (iPSC)-derived cardiomyocytes to model NS RAF1-associated HCM and to further delineate the molecular mechanisms underlying the disease.","explanation":"Supports mutation-specific mechanistic modeling in Noonan iPSC-cardiomyocytes."}]}],"findings_text":["Noonan iPSC-cardiomyocytes capture cardiomyopathy-linked cell-cycle and signaling defects in a genotype-resolved human cardiac model"],"evidence":[{"reference":"PMID:34988410","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/34988410","reference_title":"Cell cycle defects underlie childhood-onset cardiomyopathy associated with Noonan syndrome.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Here, through analysis of sarcomeric myosin conformational states, histopathology, and gene expression in left ventricular myocardial tissue from NS-CM, HCM, and normal hearts complemented with disease modeling in cardiomyocytes differentiated from patient-derived PTPN11 N308S/+ induced pluripotent stem cells, we demonstrate distinct disease phenotypes between NS-CM and HCM and uncover cell cycle defects as a potential driver of NS-CM.","explanation":"Supports this as a first-class Noonan iPSC-cardiomyocyte model entry."},{"reference":"PMID:31163979","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/31163979","reference_title":"Inducible Pluripotent Stem Cell-Derived Cardiomyocytes Reveal Aberrant Extracellular Regulated Kinase 5 and Mitogen-Activated Protein Kinase Kinase 1/2 Signaling Concomitantly Promote Hypertrophic Cardiomyopathy in RAF1-Associated Noonan Syndrome.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"METHODS: We used patient-derived RAF1S257L/+ and CRISPR-Cas9-generated isogenic control inducible pluripotent stem cell (iPSC)-derived cardiomyocytes to model NS RAF1-associated HCM and to further delineate the molecular mechanisms underlying the disease.","explanation":"Establishes the model as informative for dissecting which arm of the ERK cascade node drives which part of the phenotype."},{"reference":"PMID:31163979","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/31163979","reference_title":"Inducible Pluripotent Stem Cell-Derived Cardiomyocytes Reveal Aberrant Extracellular Regulated Kinase 5 and Mitogen-Activated Protein Kinase Kinase 1/2 Signaling Concomitantly Promote Hypertrophic Cardiomyopathy in RAF1-Associated Noonan Syndrome.","supports":"REFUTE","evidence_source":"IN_VITRO","snippet":"Importantly, although ERK1/2 activation was strongly reduced, there was no significant effect on hypertrophy in RAF1S257L/+ iCMs in response to treatment with either PD98059 or Trametinib (Fig.4C–D), suggesting that MEK1/2-ERK1/2 activation is not the principal driver of hypertrophy in NS-associated RAF1 mutations.","explanation":"Directly reports the negative result for ERK1/2 as the hypertrophy driver."},{"reference":"PMID:31163979","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/31163979","reference_title":"Inducible Pluripotent Stem Cell-Derived Cardiomyocytes Reveal Aberrant Extracellular Regulated Kinase 5 and Mitogen-Activated Protein Kinase Kinase 1/2 Signaling Concomitantly Promote Hypertrophic Cardiomyopathy in RAF1-Associated Noonan Syndrome.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"the enlarged cardiomyocyte phenotype is a direct consequence of increased extracellular regulated kinase 5 (ERK5) signaling, a pathway not previously known to be involved in NS.","explanation":"Reports the alternative driver the paper identifies for the hypertrophic phenotype."}],"evidence_text":["Here, through analysis of sarcomeric myosin conformational states, histopathology, and gene expression in left ventricular myocardial tissue from NS-CM, HCM, and normal hearts complemented with disease modeling in cardiomyocytes differentiated from patient-derived PTPN11 N308S/+ induced pluripotent stem cells, we demonstrate distinct disease phenotypes between NS-CM and HCM and uncover cell cycle defects as a potential driver of NS-CM.","METHODS: We used patient-derived RAF1S257L/+ and CRISPR-Cas9-generated isogenic control inducible pluripotent stem cell (iPSC)-derived cardiomyocytes to model NS RAF1-associated HCM and to further delineate the molecular mechanisms underlying the disease.","Importantly, although ERK1/2 activation was strongly reduced, there was no significant effect on hypertrophy in RAF1S257L/+ iCMs in response to treatment with either PD98059 or Trametinib (Fig.4C–D), suggesting that MEK1/2-ERK1/2 activation is not the principal driver of hypertrophy in NS-associated RAF1 mutations.","the enlarged cardiomyocyte phenotype is a direct consequence of increased extracellular regulated kinase 5 (ERK5) signaling, a pathway not previously known to be involved in NS.","Supports this as a first-class Noonan iPSC-cardiomyocyte model entry.","Establishes the model as informative for dissecting which arm of the ERK cascade node drives which part of the phenotype.","Directly reports the negative result for ERK1/2 as the hypertrophy driver.","Reports the alternative driver the paper identifies for the hypertrophic phenotype."],"evidence_status":"Evidence 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This mislocalization caused an imbalance in potassium and\nchloride ion levels in the proband's cells.","explanation":"The proband-cell assay directly reports cellular ion imbalance downstream of mutant mislocalization."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Agenesis_of_the_Corpus_Callosum_with_Peripheral_Neuropathy","model_node_id":"model:kb/disorders/Agenesis_of_the_Corpus_Callosum_with_Peripheral_Neuropathy.yaml:p.H371R proband-cell functional assay","focus_node_id":"node:disorder%3AAgenesis_of_the_Corpus_Callosum_with_Peripheral_Neuropathy:pathophysiology:Impaired%20KCC3-mediated%20ion%20transport%20and%20ionic%20homeostasis","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Agenesis_of_the_Corpus_Callosum_with_Peripheral_Neuropathy.html#pathograph","nodes":[{"id":"model:kb/disorders/Agenesis_of_the_Corpus_Callosum_with_Peripheral_Neuropathy.yaml:p.H371R proband-cell functional assay","kind":"experimental_model","kind_label":"NAM model","label":"p.H371R proband-cell functional assay","description":"Proband-derived cells carrying homozygous p.H371R SLC12A6 were compared with wild type for mutant-protein localization, ion-transport function, and potassium/chloride ion levels. The cached abstract does not identify the cell type.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Agenesis_of_the_Corpus_Callosum_with_Peripheral_Neuropathy.html#experimental-model-p-h371r-proband-cell-functional-assay","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAgenesis_of_the_Corpus_Callosum_with_Peripheral_Neuropathy:pathophysiology:Impaired%20KCC3-mediated%20ion%20transport%20and%20ionic%20homeostasis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired KCC3-mediated ion transport and ionic homeostasis","description":"KCC3 normally mediates electroneutral potassium and chloride efflux in neurons. 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This mislocalization caused an imbalance in potassium and\nchloride ion levels in the proband's cells.","explanation":"The proband-cell assay directly reports cellular ion imbalance downstream of mutant mislocalization."}],"evidence_text":["type, the mutant protein was mislocalized to the cytoplasm, disrupting its ion\ntransport function.","transport function. This mislocalization caused an imbalance in potassium and\nchloride ion levels in the proband's cells.","The patient-cell assay supports mutant mislocalization and transport loss.","The proband-cell assay directly reports cellular ion imbalance downstream of mutant mislocalization."],"evidence_status":"Evidence recorded","metadata_completeness":60,"metadata_present":["Model category","Cell type","Cell source","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Organism","Anatomy","Culture system"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Agenesis_of_the_Corpus_Callosum_with_Peripheral_Neuropathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Agenesis_of_the_Corpus_Callosum_with_Peripheral_Neuropathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Agenesis_of_the_Corpus_Callosum_with_Peripheral_Neuropathy.html#experimental-model-p-h371r-proband-cell-functional-assay","source_anchor":"experimental-model-p-h371r-proband-cell-functional-assay"},{"id":"model:kb/disorders/Autosomal_Recessive_Nonsyndromic_Hearing_Loss_88.yaml:p.Leu265Ser expression in cochlear explants","name":"p.Leu265Ser expression in cochlear explants","description":"Organotypic cochlear explants transfected with wild-type or p.Leu265Ser GFP-ELMOD3 reveal variant-specific failure of stereociliary targeting.","notes":null,"context_id":"disorder:Autosomal_Recessive_Nonsyndromic_Hearing_Loss_88","context_kind":"Disorder","disease_name":"Autosomal Recessive Nonsyndromic Hearing Loss 88","disease_synonyms":["DFNB88","deafness, autosomal recessive 88","autosomal recessive deafness 88","autosomal recessive nonsyndromic deafness caused by mutation in ELMOD3","ELMOD3 autosomal recessive nonsyndromic deafness"],"disease_term":{"id":"MONDO:0014182","label":"autosomal recessive nonsyndromic hearing loss 88","display_label":"autosomal recessive nonsyndromic hearing loss 88","url":"http://purl.obolibrary.org/obo/MONDO_0014182"},"experimental_model_type":"PRIMARY_CELL_CULTURE","experimental_model_type_label":"Primary-cell culture","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[{"id":"UBERON:0002227","label":"spiral organ of cochlea","display_label":"spiral organ of Corti","url":"http://purl.obolibrary.org/obo/UBERON_0002227"}],"linked_anatomy_labels":["spiral organ of cochlea"],"anatomy":[{"id":"UBERON:0002227","label":"spiral organ of cochlea","display_label":"spiral organ of Corti","url":"http://purl.obolibrary.org/obo/UBERON_0002227"}],"anatomy_labels":["spiral organ of cochlea"],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[{"id":"CL:0000589","label":"cochlear inner hair cell","display_label":"cochlear inner hair cell","url":"http://purl.obolibrary.org/obo/CL_0000589"},{"id":"CL:0000601","label":"cochlear outer hair cell","display_label":"cochlear outer hair cell","url":"http://purl.obolibrary.org/obo/CL_0000601"}],"linked_cell_type_labels":["cochlear inner hair cell","cochlear outer hair cell"],"cell_types":[{"id":"CL:0000589","label":"cochlear inner hair cell","display_label":"cochlear inner hair cell","url":"http://purl.obolibrary.org/obo/CL_0000589"},{"id":"CL:0000601","label":"cochlear outer hair cell","display_label":"cochlear outer hair cell","url":"http://purl.obolibrary.org/obo/CL_0000601"}],"cell_type_labels":["cochlear inner hair cell","cochlear outer hair cell"],"conditions":[],"cell_source":"P2 C57BL/6J mouse organ-of-Corti explants","source_category":"Primary / biopsy-derived","culture_system":null,"publication":"PMID:24039609","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/24039609","mechanisms":[{"target":"Impaired ELMOD3 Targeting to Stereocilia","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Recessive_Nonsyndromic_Hearing_Loss_88.html#pathophysiology-impaired-elmod3-targeting-to-stereocilia","relationship":"MEASURES","relationship_label":"Measures","fidelity":"MODERATE","fidelity_label":"Moderate","description":"Tagged patient-variant protein remains predominantly cytosolic rather than concentrating in stereocilia.","limitations":"Cultured mouse tissue with overexpressed human protein; 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Wild-type rodent immunolocalization supports a hair-bundle context, but the antibody recognized isoform b rather than all ELMOD3 isoforms. The targeting defect is distinct from loss of direct actin binding: weak F-actin co-sedimentation of recombinant protein was unchanged by the variant.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Recessive_Nonsyndromic_Hearing_Loss_88.html#pathophysiology-impaired-elmod3-targeting-to-stereocilia","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3AAutosomal_Recessive_Nonsyndromic_Hearing_Loss_88:pathophysiology:Disorganized%20Stereociliary%20Actin%20Cytoskeleton","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Disorganized Stereociliary Actin Cytoskeleton","description":"Elmod3-null mice show weaker cochlear phalloidin staining, involving hair cells, supporting cells, spiral ganglion and spiral ligament. 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The pellets these cells form are rich in glycosaminoglycan and still structurally poor, which is the cellular-level version of the whole entry's point that the defect is in matrix assembly rather than in bulk synthesis.","url":"https://dismech.monarchinitiative.org/pages/disorders/ACAN-Related_Short_Stature_Spectrum.html#pathophysiology-aggrecan-retention-in-the-chondrocyte-endoplasmic-reticulum","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AACAN-Related_Short_Stature_Spectrum:pathophysiology:Heterozygous%20ACAN%20Variants","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Heterozygous ACAN Variants","description":"Heterozygous pathogenic ACAN variants include truncating, splice-site and missense alleles distributed across the gene. Missense variants associated with familial osteochondritis dissecans are enriched in the G3 domain, but neither all missense variants nor all familial osteochondritis dissecans variants are restricted to that domain. Variant class, domain and experimental system must be distinguished when interpreting functional effects.","url":"https://dismech.monarchinitiative.org/pages/disorders/ACAN-Related_Short_Stature_Spectrum.html#pathophysiology-heterozygous-acan-variants","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AACAN-Related_Short_Stature_Spectrum:pathophysiology:Reduced%20Secretion%20of%20G3-Domain%20Variant%20Aggrecan","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced Secretion of G3-Domain Variant Aggrecan","description":"Selected G3 variants are secreted less efficiently in recombinant expression assays, with severity depending on the splice construct. In the 2022 pilot explant experiment, a patient carrying p.V2455M had less variant than wild-type aggrecan in both cartilage and conditioned medium. This is a within-patient allelic comparison, not a measurement in cartilage from each of the three newly described families.","url":"https://dismech.monarchinitiative.org/pages/disorders/ACAN-Related_Short_Stature_Spectrum.html#pathophysiology-reduced-secretion-of-g3-domain-variant-aggrecan","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/ACAN-Related_Short_Stature_Spectrum.yaml:Patient BM-MSC and iPSC-derived chondrocyte model of familial osteochondritis dissecans","source_id":"model:kb/disorders/ACAN-Related_Short_Stature_Spectrum.yaml:Patient BM-MSC and iPSC-derived chondrocyte model of familial osteochondritis 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experiment.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AACAN-Related_Short_Stature_Spectrum:0:2","source_id":"node:disorder%3AACAN-Related_Short_Stature_Spectrum:pathophysiology:Heterozygous%20ACAN%20Variants","target_id":"node:disorder%3AACAN-Related_Short_Stature_Spectrum:pathophysiology:Aggrecan%20Retention%20in%20the%20Chondrocyte%20Endoplasmic%20Reticulum","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[2]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Patient-derived cells carrying p.V2303M show ER aggrecan accumulation.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1}]}}],"mechanism_names":["Aggrecan Retention in the Chondrocyte Endoplasmic Reticulum"],"relationships":["Recapitulates"],"fidelities":["Moderate"],"biological_scales":["Cellular"],"system_context_sources":["Model-level cell type","Linked mechanism cell type","Linked mechanism biological scale"],"modeled_system_labels":["chondrocyte","Cellular"],"biological_process_terms":[{"id":"GO:0034976","label":"response to endoplasmic reticulum stress","display_label":"response to endoplasmic reticulum stress","url":"http://purl.obolibrary.org/obo/GO_0034976"}],"biological_processes":["response to endoplasmic reticulum stress"],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":["Intracellular aggrecan localisation in differentiated chondrocytes","Extracellular matrix aggrecan content"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:27388238","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/27388238","reference_title":"Chondrocytes Derived From Mesenchymal Stromal Cells and Induced Pluripotent Cells of Patients With Familial Osteochondritis Dissecans Exhibit an Endoplasmic Reticulum Stress Response and Defective Matrix Assembly.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"It is associated with a heterozygous mutation in the ACAN gene, resulting in a Val-Met replacement in the C-type lectin domain of aggrecan.","explanation":"Establishes that the cells carry the disease allele of this spectrum, which is what makes the model informative for these nodes at 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was evident that large amounts of aggrecan accumulated within the endoplasmic reticulum of chondrocytes differentiated from both BM-MSCs and iPSCs.","explanation":"The measurement this readout records, in both derivation routes."},{"reference":"PMID:27388238","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/27388238","reference_title":"Chondrocytes Derived From Mesenchymal Stromal Cells and Induced Pluripotent Cells of Patients With Familial Osteochondritis Dissecans Exhibit an Endoplasmic Reticulum Stress Response and Defective Matrix Assembly.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"In turn, there was a marked absence of aggrecan in the extracellular matrix.","explanation":"Records the depletion of matrix aggrecan alongside the intracellular accumulation."}],"evidence_text":["It is associated with a heterozygous mutation in the ACAN gene, resulting in a Val-Met replacement in the C-type lectin domain of aggrecan.","The results suggest that FOCD is a chondrocyte aggrecanosis with associated matrix dysregulation.","Second, it was evident that large amounts of aggrecan accumulated within the endoplasmic reticulum of chondrocytes differentiated from both BM-MSCs and iPSCs.","In turn, there was a marked absence of aggrecan in the extracellular matrix.","Establishes that the cells carry the disease allele of this spectrum, which is what makes the model informative for these nodes at all.","The authors' own summary of what the model shows, which is the claim the link above carries.","The measurement this readout records, in both derivation routes.","Records the depletion of matrix aggrecan alongside the intracellular accumulation."],"evidence_status":"Evidence recorded","metadata_completeness":70,"metadata_present":["Model category","Organism","Cell type","Cell source","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Anatomy","Culture system"],"dataset_context":"None recorded in same 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The limitation is that colony formation did not correlate with haemoglobin, platelet or neutrophil counts, so the assay reports the cellular lesion rather than predicting the clinical blood count.","notes":null,"context_id":"disorder:Cartilage-Hair_Hypoplasia","context_kind":"Disorder","disease_name":"Cartilage-hair hypoplasia","disease_synonyms":["CHH","metaphyseal chondrodysplasia, McKusick type","McKusick Type Metaphyseal Chondrodysplasia","autosomal recessive metaphyseal chondrodysplasia"],"disease_term":{"id":"MONDO:0009595","label":"cartilage-hair hypoplasia","display_label":"cartilage-hair hypoplasia","url":"http://purl.obolibrary.org/obo/MONDO_0009595"},"experimental_model_type":"PRIMARY_CELL_CULTURE","experimental_model_type_label":"Primary-cell culture","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},"organism_label":"Homo sapiens","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[{"id":"CL:0000038","label":"erythroid progenitor cell","display_label":"erythroid progenitor cell","url":"http://purl.obolibrary.org/obo/CL_0000038"}],"model_cell_type_labels":["erythroid progenitor cell"],"linked_cell_types":[{"id":"CL:0000038","label":"erythroid progenitor cell","display_label":"erythroid progenitor cell","url":"http://purl.obolibrary.org/obo/CL_0000038"}],"linked_cell_type_labels":["erythroid progenitor cell"],"cell_types":[{"id":"CL:0000038","label":"erythroid progenitor cell","display_label":"erythroid progenitor cell","url":"http://purl.obolibrary.org/obo/CL_0000038"}],"cell_type_labels":["erythroid progenitor cell"],"conditions":["Patient-derived progenitors","Normal progenitor controls","Standard versus more effectively stimulated culture"],"cell_source":"Bone marrow and peripheral blood from patients with cartilage-hair hypoplasia","source_category":"Patient-derived","culture_system":"Semi-solid colony-forming assay for erythroid, megakaryocyte and granulocyte-macrophage progenitors","publication":"PMID:7895753","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/7895753","mechanisms":[{"target":"Multilineage Bone Marrow Progenitor Failure","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Cartilage-hair_hypoplasia.html#pathophysiology-multilineage-bone-marrow-progenitor-failure","relationship":"RECAPITULATES","relationship_label":"Recapitulates","fidelity":"HIGH","fidelity_label":"High","description":"Measures colony formation across erythroid, megakaryocyte and granulocyte-macrophage lineages in patient-derived progenitors.","limitations":"Ex vivo culture in eight patients; the defect did not track peripheral blood counts, so it cannot serve as a severity readout for an individual patient.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[{"id":"CL:0000038","label":"erythroid progenitor cell","display_label":"erythroid progenitor cell","url":"http://purl.obolibrary.org/obo/CL_0000038"}],"biological_processes":[{"id":"GO:0030218","label":"erythrocyte differentiation","display_label":"erythrocyte differentiation","url":"http://purl.obolibrary.org/obo/GO_0030218"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Erythroid, megakaryocyte and granulocyte-macrophage colony formation","description":null,"target":"Multilineage Bone Marrow Progenitor Failure","direction":"DECREASED","interpretation":"Functional demonstration of the multilineage progenitor defect in patient cells.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:7895753","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/7895753","reference_title":"Defective in-vitro colony formation of haematopoietic progenitors in patients with cartilage-hair hypoplasia and history of anaemia.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"All patients showed decreased erythroid and megakaryocyte colony formation. Only one patient had a normal granulocyte-macrophage growth, while the others showed decreased numbers of colonies.","explanation":"Reports the measured colony deficit across all three lineages."}],"notes":null}],"evidence":[{"reference":"PMID:7895753","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/7895753","reference_title":"Defective in-vitro colony formation of haematopoietic progenitors in patients with cartilage-hair hypoplasia and history of anaemia.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The present study shows defective in vitro colony formation in all myeloid lineages in patients with CHH, which is in accordance with the suggestion of a common cell proliferation defect in CHH.","explanation":"Supports treating this assay as informative for the marrow-failure node."},{"reference":"PMID:7895753","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/7895753","reference_title":"Defective in-vitro colony formation of haematopoietic progenitors in patients with cartilage-hair hypoplasia and history of anaemia.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"All patients showed decreased erythroid and megakaryocyte colony formation. Only one patient had a normal granulocyte-macrophage growth, while the others showed decreased numbers of colonies.","explanation":"Reports the measured colony deficit across all three lineages."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Cartilage-Hair_Hypoplasia","model_node_id":"model:kb/disorders/Cartilage-Hair_Hypoplasia.yaml:Patient bone marrow progenitor colony-forming assay","focus_node_id":"node:disorder%3ACartilage-Hair_Hypoplasia:pathophysiology:Multilineage%20Bone%20Marrow%20Progenitor%20Failure","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Cartilage-hair_hypoplasia.html#pathograph","nodes":[{"id":"model:kb/disorders/Cartilage-Hair_Hypoplasia.yaml:Patient bone marrow progenitor colony-forming assay","kind":"experimental_model","kind_label":"NAM model","label":"Patient bone marrow progenitor colony-forming assay","description":"The closest thing CHH has to a functional test of the marrow arm, and its value lies in a specific control: showing progenitor numbers are normal or increased while colony formation fails separates a proliferation defect from progenitor depletion. 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Bone marrow erythroid hypoplasia is found in all severely anemic patients who are examined.","url":"https://dismech.monarchinitiative.org/pages/disorders/Cartilage-hair_hypoplasia.html#pathophysiology-multilineage-bone-marrow-progenitor-failure","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACartilage-Hair_Hypoplasia:phenotype:Anemia","kind":"phenotype","kind_label":"Phenotype","label":"Anemia","description":"Anemia arising from defective erythroid colony formation, most severe in early childhood and typically absent in adults. 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Residual mRNA cleavage activity, not rRNA activity, predicts hair hypoplasia, immunodeficiency and haematological abnormality across the spectrum, which is why CHH is the end where those features are expected rather than conditional.","url":"https://dismech.monarchinitiative.org/pages/disorders/Cartilage-hair_hypoplasia.html#pathophysiology-impaired-cyclin-b2-mrna-cleavage-and-g2-to-m-delay","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACartilage-Hair_Hypoplasia:phenotype:Macrocytic%20anemia","kind":"phenotype","kind_label":"Phenotype","label":"Macrocytic anemia","description":"The anemia of CHH is characteristically macrocytic, and macrocytosis occurs even in patients without anemia. 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They reproduce UV hypersensitivity and the recovery-of-RNA-synthesis defect with relatively preserved unscheduled DNA synthesis, and they support complementation testing.","notes":null,"context_id":"disorder:UV-Sensitive_Syndrome","context_kind":"Disorder","disease_name":"UV-Sensitive Syndrome","disease_synonyms":["UVSS","UV-sensitive syndrome","UV sensitive syndrome","Ultraviolet-sensitive syndrome"],"disease_term":{"id":"MONDO:0015797","label":"UV-sensitive syndrome","display_label":"UV-sensitive syndrome","url":"http://purl.obolibrary.org/obo/MONDO_0015797"},"experimental_model_type":"PRIMARY_CELL_CULTURE","experimental_model_type_label":"Primary-cell culture","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},"organism_label":"Homo sapiens","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[{"id":"UBERON:0002097","label":"skin of body","display_label":"skin of body","url":"http://purl.obolibrary.org/obo/UBERON_0002097"}],"linked_anatomy_labels":["skin of body"],"anatomy":[{"id":"UBERON:0002097","label":"skin of body","display_label":"skin of body","url":"http://purl.obolibrary.org/obo/UBERON_0002097"}],"anatomy_labels":["skin of body"],"tissue_label":null,"model_cell_types":[{"id":"CL:0000057","label":"fibroblast","display_label":"dermal fibroblast","url":"http://purl.obolibrary.org/obo/CL_0000057"}],"model_cell_type_labels":["fibroblast"],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[{"id":"CL:0000057","label":"fibroblast","display_label":"dermal fibroblast","url":"http://purl.obolibrary.org/obo/CL_0000057"}],"cell_type_labels":["fibroblast"],"conditions":[],"cell_source":null,"source_category":"Primary / biopsy-derived","culture_system":null,"publication":"PMID:15486090","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/15486090","mechanisms":[{"target":"Persistent Transcription Blockage After UV Exposure","target_url":"https://dismech.monarchinitiative.org/pages/disorders/UV-Sensitive_Syndrome.html#pathophysiology-persistent-transcription-blockage-after-uv-exposure","relationship":"RECAPITULATES","relationship_label":"Recapitulates","fidelity":"HIGH","fidelity_label":"High","description":"The cellular phenotype these lines display is the node itself: transcription fails to recover after UV while global-genome repair stays near normal.","limitations":"Cultured fibroblasts carry neither the epidermal architecture in which the disease is expressed nor a lifetime of intermittent solar exposure, and the assays use acute high-dose 254 nm UV rather than sunlight.","biological_scale":"CELLULAR","anatomy":[{"id":"UBERON:0002097","label":"skin of body","display_label":"skin of body","url":"http://purl.obolibrary.org/obo/UBERON_0002097"}],"cell_types":[],"biological_processes":[{"id":"GO:0070914","label":"UV-damage excision repair","display_label":"UV-damage excision repair","url":"http://purl.obolibrary.org/obo/GO_0070914"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[],"evidence":[{"reference":"PMID:15486090","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/15486090","reference_title":"Complete absence of Cockayne syndrome group B gene product gives rise to UV-sensitive syndrome but not Cockayne syndrome.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"UVsS cells show UV hypersensitivity and defective transcription-coupled DNA repair of UV damage.","explanation":"States the phenotype these patient lines display, which is what makes them informative for this node."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:UV-Sensitive_Syndrome","model_node_id":"model:kb/disorders/UV-Sensitive_Syndrome.yaml:Patient dermal fibroblast lines","focus_node_id":"node:disorder%3AUV-Sensitive_Syndrome:pathophysiology:Persistent%20Transcription%20Blockage%20After%20UV%20Exposure","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/UV-Sensitive_Syndrome.html#pathograph","nodes":[{"id":"model:kb/disorders/UV-Sensitive_Syndrome.yaml:Patient dermal fibroblast lines","kind":"experimental_model","kind_label":"NAM model","label":"Patient dermal fibroblast lines","description":"Primary fibroblasts cultured from affected individuals. These are the systems in which the disease was originally defined: UVs1KO, which carries the homozygous null CSB allele, and Kps3, which has normal CSB protein and established that the syndrome is genetically heterogeneous. They reproduce UV hypersensitivity and the recovery-of-RNA-synthesis defect with relatively preserved unscheduled DNA synthesis, and they support complementation testing.","url":"https://dismech.monarchinitiative.org/pages/disorders/UV-Sensitive_Syndrome.html#experimental-model-patient-dermal-fibroblast-lines","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AUV-Sensitive_Syndrome:pathophysiology:Persistent%20Transcription%20Blockage%20After%20UV%20Exposure","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Persistent Transcription Blockage After UV Exposure","description":"Transcription of the damaged strand does not recover after UV irradiation. This is the defining cellular phenotype and the basis of the recovery-of-RNA-synthesis assay, which is abnormal while unscheduled DNA synthesis (reflecting global-genome repair) stays near normal.","url":"https://dismech.monarchinitiative.org/pages/disorders/UV-Sensitive_Syndrome.html#pathophysiology-persistent-transcription-blockage-after-uv-exposure","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AUV-Sensitive_Syndrome:pathophysiology:Failure%20to%20Process%20Stalled%20RNA%20Polymerase%20II","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Failure to Process Stalled RNA Polymerase II","description":"Repair normally proceeds by an ordered handover: CSB binds the stalled polymerase and recruits CSA, CSA loads UVSSA, ELOF1 positions UVSSA and the CRL4-CSA ligase so that the polymerase is ubiquitylated and inactivated, and UVSSA then recruits TFIIH to open the DNA. Losing any one of CSB, CSA or UVSSA breaks this chain, so the arrested polymerase is neither inactivated nor cleared and the repair machinery is never delivered to the lesion.","url":"https://dismech.monarchinitiative.org/pages/disorders/UV-Sensitive_Syndrome.html#pathophysiology-failure-to-process-stalled-rna-polymerase-ii","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AUV-Sensitive_Syndrome:pathophysiology:UV-Induced%20Keratinocyte%20Apoptosis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"UV-Induced Keratinocyte Apoptosis","description":"Sustained transcription arrest in UV-exposed epidermal keratinocytes triggers stress signalling and cell death, producing the exaggerated sunburn response. This last step is inferred from the repair biology and the clinical picture rather than traced directly in patient skin, and is the weakest link in the chain.","url":"https://dismech.monarchinitiative.org/pages/disorders/UV-Sensitive_Syndrome.html#pathophysiology-uv-induced-keratinocyte-apoptosis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/UV-Sensitive_Syndrome.yaml:Patient dermal fibroblast lines","source_id":"model:kb/disorders/UV-Sensitive_Syndrome.yaml:Patient dermal fibroblast lines","target_id":"node:disorder%3AUV-Sensitive_Syndrome:pathophysiology:Persistent%20Transcription%20Blockage%20After%20UV%20Exposure","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"HIGH","causal_link_type":null,"causal_link_type_label":null,"description":"The cellular phenotype these lines display is the node itself: transcription fails to recover after UV while global-genome repair stays near normal.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AUV-Sensitive_Syndrome:1:0","source_id":"node:disorder%3AUV-Sensitive_Syndrome:pathophysiology:Failure%20to%20Process%20Stalled%20RNA%20Polymerase%20II","target_id":"node:disorder%3AUV-Sensitive_Syndrome:pathophysiology:Persistent%20Transcription%20Blockage%20After%20UV%20Exposure","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[0]","label":"Directly 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Exposure"],"relationships":["Recapitulates"],"fidelities":["High"],"biological_scales":["Cellular"],"system_context_sources":["Model-level cell type","Linked mechanism anatomy","Linked mechanism biological scale"],"modeled_system_labels":["skin of body","fibroblast","Cellular"],"biological_process_terms":[{"id":"GO:0070914","label":"UV-damage excision repair","display_label":"UV-damage excision repair","url":"http://purl.obolibrary.org/obo/GO_0070914"}],"biological_processes":["UV-damage excision repair"],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":[],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:15486090","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/15486090","reference_title":"Complete absence of Cockayne syndrome group B gene product gives rise to UV-sensitive syndrome but not Cockayne syndrome.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"On the other hand, no mutation in the CSB cDNA and a normal amount of CSB protein was detected in Kps3, a UVsS cell line obtained from an unrelated patient, indicating genetic heterogeneity in UVsS.","explanation":"Names one of the patient lines and reports the result that established genetic heterogeneity, showing what these models were used to decide."},{"reference":"PMID:15486090","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/15486090","reference_title":"Complete absence of Cockayne syndrome group B gene product gives rise to UV-sensitive syndrome but not Cockayne syndrome.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"UVsS cells show UV hypersensitivity and defective transcription-coupled DNA repair of UV damage.","explanation":"States the phenotype these patient lines display, which is what makes them informative for this node."}],"evidence_text":["On the other hand, no mutation in the CSB cDNA and a normal amount of CSB protein was detected in Kps3, a UVsS cell line obtained from an unrelated patient, indicating genetic heterogeneity in UVsS.","UVsS cells show UV hypersensitivity and defective transcription-coupled DNA repair of UV damage.","Names one of the patient lines and reports the result that established genetic heterogeneity, showing what these models were used to decide.","States the phenotype these patient lines display, which is what makes them informative for this node."],"evidence_status":"Evidence recorded","metadata_completeness":70,"metadata_present":["Model category","Organism","Anatomy","Cell type","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Cell source","Culture system"],"dataset_context":"Available in same entry","context_dataset_ids":["dataset:geo:gse111989","dataset:geo:gse121960","dataset:geo:gse132840","dataset:geo:gse168861"],"candidate_dataset_ids":[],"source_path":"kb/disorders/UV-Sensitive_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/UV-Sensitive_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/UV-Sensitive_Syndrome.html#experimental-model-patient-dermal-fibroblast-lines","source_anchor":"experimental-model-patient-dermal-fibroblast-lines"},{"id":"model:kb/disorders/Spastic_Paraparesis-cataracts-speech_Delay_Syndrome.yaml:Patient dermal fibroblast lines with FAR1 p.Arg480His and p.Arg480Cys","name":"Patient dermal fibroblast lines with FAR1 p.Arg480His and p.Arg480Cys","description":"Skin fibroblasts from patients 1 to 3 (two p.Arg480His, one p.Arg480Cys) against six anonymised control lines. Every functional claim in this entry comes from this model - plasmalogen measurement by gas chromatography, FAR1 enzyme assay, immunoblot, immunofluorescence, the HDG feedback challenge, and lipidomics with C17:0 labelling.\nOn animal models, and the claim needs stating precisely because the obvious reading of it is wrong. There is no animal model of *this* disease and no cell line carrying an engineered Arg480 allele. FAR1 itself is not model-less: a Far1 knockout mouse exists, is subviable with growth retardation and male infertility, and its authors present it as a model of ether lipid *deficiency*. That is the recessive arm, the mechanistic inverse of this disease, and it cannot substitute for a model of Arg480 gain of function.","notes":null,"context_id":"disorder:Spastic_Paraparesis-cataracts-speech_Delay_Syndrome","context_kind":"Disorder","disease_name":"Spastic Paraparesis-Cataracts-Speech Delay Syndrome","disease_synonyms":["CSPSD","Fatty acyl-CoA reductase 1 superactivity","FAR1 upregulation","Cataracts, spastic paraparesis, and speech delay","Autosomal dominant FAR1-related disorder"],"disease_term":{"id":"MONDO:0036212","label":"spastic paraparesis-cataracts-speech delay syndrome","display_label":"Spastic paraparesis-cataracts-speech delay syndrome","url":"http://purl.obolibrary.org/obo/MONDO_0036212"},"experimental_model_type":"PRIMARY_CELL_CULTURE","experimental_model_type_label":"Primary-cell culture","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":null,"source_category":"Primary / biopsy-derived","culture_system":null,"publication":null,"publication_url":null,"mechanisms":[{"target":"Loss of Plasmalogen-Dependent Feedback Degradation of FAR1","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Spastic_Paraparesis-Cataracts-Speech_Delay_Syndrome.html#pathophysiology-loss-of-plasmalogen-dependent-feedback-degradation-of-far1","relationship":"RECAPITULATES","relationship_label":"Recapitulates","fidelity":"HIGH","fidelity_label":"High","description":"The HDG challenge is a genuine perturbation experiment rather than an observation: it raises plasmalogen by a route that bypasses FAR1, so the feedback loop is stimulated directly, and the patient cells' failure to respond isolates the regulatory defect from the enzyme's activity.","limitations":"Fibroblasts are not the affected tissue. Nothing in this model addresses why the corticospinal tract and the lens fail while the fibroblast, which carries the same lipid abnormality, is viable and unremarkable - and that gap is the whole distance between the biochemistry and the disease. The p.Arg480Leu and p.Arg480Ser alleles have never been assayed, because no fibroblasts were available.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0030163","label":"protein catabolic process","display_label":"plasmalogen-triggered degradation of FAR1","url":"http://purl.obolibrary.org/obo/GO_0030163"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"FAR1 protein level after HDG-induced plasmalogen loading","description":null,"target":"Loss of Plasmalogen-Dependent Feedback Degradation of FAR1","direction":"UNCHANGED","interpretation":"A real negative result. Controls dropped FAR1 by about 40 percent; patient cells held it at 101 percent of baseline despite a comparable plasmalogen rise.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:33239752","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33239752","reference_title":"An autosomal dominant neurological disorder caused by de novo variants in FAR1 resulting in uncontrolled synthesis of ether lipids.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"In the patients' cells, treatment with HDG also increased C16:0-plasmalogen levels 130-224% (mean ± SD: 160 ± 35%) (Fig. 3c), but this did not result in a consistent decrease of FAR1 protein levels (mean ± SD: 101 ± 17%) (Fig. 3a, b).","explanation":"The measurement underlying this readout, including confirmation that the stimulus worked."}],"notes":null}],"evidence":[{"reference":"PMID:33239752","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33239752","reference_title":"An autosomal dominant neurological disorder caused by de novo variants in FAR1 resulting in uncontrolled synthesis of ether lipids.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We studied the effect of the identified FAR1 variants in fibroblasts of patients 1-3","explanation":"Establishes which patients the model represents, which bounds what it can be informative about. The same sentence records the alleles as two p.Arg480His and one p.Arg480Cys; that part is not quoted because the source writes the counts in square brackets, which the validator strips."},{"reference":"PMID:33239752","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33239752","reference_title":"An autosomal dominant neurological disorder caused by de novo variants in FAR1 resulting in uncontrolled synthesis of ether lipids.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"In the patients' cells, treatment with HDG also increased C16:0-plasmalogen levels 130-224% (mean ± SD: 160 ± 35%) (Fig. 3c), but this did not result in a consistent decrease of FAR1 protein levels (mean ± SD: 101 ± 17%) (Fig. 3a, b).","explanation":"The measurement underlying this readout, including confirmation that the stimulus worked."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Spastic_Paraparesis-cataracts-speech_Delay_Syndrome","model_node_id":"model:kb/disorders/Spastic_Paraparesis-cataracts-speech_Delay_Syndrome.yaml:Patient dermal fibroblast lines with FAR1 p.Arg480His and p.Arg480Cys","focus_node_id":"node:disorder%3ASpastic_Paraparesis-cataracts-speech_Delay_Syndrome:pathophysiology:Loss%20of%20Plasmalogen-Dependent%20Feedback%20Degradation%20of%20FAR1","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Spastic_Paraparesis-Cataracts-Speech_Delay_Syndrome.html#pathograph","nodes":[{"id":"model:kb/disorders/Spastic_Paraparesis-cataracts-speech_Delay_Syndrome.yaml:Patient dermal fibroblast lines with FAR1 p.Arg480His and p.Arg480Cys","kind":"experimental_model","kind_label":"NAM model","label":"Patient dermal fibroblast lines with FAR1 p.Arg480His and p.Arg480Cys","description":"Skin fibroblasts from patients 1 to 3 (two p.Arg480His, one p.Arg480Cys) against six anonymised control lines. Every functional claim in this entry comes from this model - plasmalogen measurement by gas chromatography, FAR1 enzyme assay, immunoblot, immunofluorescence, the HDG feedback challenge, and lipidomics with C17:0 labelling.\nOn animal models, and the claim needs stating precisely because the obvious reading of it is wrong. There is no animal model of *this* disease and no cell line carrying an engineered Arg480 allele. FAR1 itself is not model-less: a Far1 knockout mouse exists, is subviable with growth retardation and male infertility, and its authors present it as a model of ether lipid *deficiency*. That is the recessive arm, the mechanistic inverse of this disease, and it cannot substitute for a model of Arg480 gain of function.","url":"https://dismech.monarchinitiative.org/pages/disorders/Spastic_Paraparesis-Cataracts-Speech_Delay_Syndrome.html#experimental-model-patient-dermal-fibroblast-lines-with-far1-p-arg480his-and-p-arg480cys","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ASpastic_Paraparesis-cataracts-speech_Delay_Syndrome:pathophysiology:Loss%20of%20Plasmalogen-Dependent%20Feedback%20Degradation%20of%20FAR1","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Loss of Plasmalogen-Dependent Feedback Degradation of FAR1","description":"The lesion, and the reason this disease exists as a separate entity from RCDP4.\nNormally, FAR1 abundance is set by a negative feedback loop: rising cellular plasmalogen triggers active degradation of FAR1 protein, so ether lipid output self-limits. The experiment that demonstrates the loop is broken here is a clean one. Loading fibroblasts with 1-O-hexadecyl-sn-glycerol raises plasmalogen by a route that bypasses FAR1 entirely, and in control cells that drops FAR1 protein by about 40 percent. In patients' cells the same treatment raised plasmalogen just as intended, and FAR1 protein did not fall.\nThe starting condition makes the point sharper still. Untreated patient cells already had plasmalogen about twice control - roughly the level that HDG-treated control cells reach - and yet held FAR1 protein at three times the HDG-treated control level. The signal was maximal and the response was absent.","url":"https://dismech.monarchinitiative.org/pages/disorders/Spastic_Paraparesis-Cataracts-Speech_Delay_Syndrome.html#pathophysiology-loss-of-plasmalogen-dependent-feedback-degradation-of-far1","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ASpastic_Paraparesis-cataracts-speech_Delay_Syndrome:pathophysiology:De%20Novo%20Heterozygous%20FAR1%20Arg480%20Variant","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"De Novo Heterozygous FAR1 Arg480 Variant","description":"Every reported allele changes the same arginine. Four patients carry c.1439G>A p.(Arg480His), seven c.1438C>T p.(Arg480Cys), one c.1439G>T p.(Arg480Leu), and a later single case p.(Arg480Ser). None is in gnomAD.\nThe residue's position is the mechanism. Arg480 sits in FAR1's predicted transmembrane domain, amino acids 466 to 483, near the edge facing the peroxisomal matrix - and the region flanking that domain on the matrix side is the part previously shown to be required for plasmalogen-dependent control of FAR1 stability. So the variants are in the regulatory element, not in the catalytic domain, which is exactly what the functional results show: catalysis intact, regulation gone.\nThat every disease allele is at one codon, and that four different substitutions there all produce the same disease, is strong evidence that the residue itself is the essential thing rather than any particular replacement amino acid.","url":"https://dismech.monarchinitiative.org/pages/disorders/Spastic_Paraparesis-Cataracts-Speech_Delay_Syndrome.html#pathophysiology-de-novo-heterozygous-far1-arg480-variant","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ASpastic_Paraparesis-cataracts-speech_Delay_Syndrome:pathophysiology:Elevated%20FAR1%20Protein%20and%20Enzyme%20Activity","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Elevated FAR1 Protein and Enzyme Activity","description":"The immediate quantitative consequence of the broken brake: more FAR1 protein on immunoblot, and FAR1 enzyme activity in patients' fibroblasts of 379, 323 and 310 pmol per hour per mg protein against control values of 74, 90 and 101 - three to four times control.\nThe `modifier` here is INCREASED, deliberately and in contrast with the node below. The claim at this node is purely quantitative: a normal enzyme, doing its normal reaction, present in larger amounts. Nothing about the enzyme itself is qualitatively altered - immunofluorescence shows normal peroxisomal targeting, and other peroxisomal functions are normal.","url":"https://dismech.monarchinitiative.org/pages/disorders/Spastic_Paraparesis-Cataracts-Speech_Delay_Syndrome.html#pathophysiology-elevated-far1-protein-and-enzyme-activity","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"}],"edges":[{"id":"model-link:0:model:kb/disorders/Spastic_Paraparesis-cataracts-speech_Delay_Syndrome.yaml:Patient dermal fibroblast lines with FAR1 p.Arg480His and p.Arg480Cys","source_id":"model:kb/disorders/Spastic_Paraparesis-cataracts-speech_Delay_Syndrome.yaml:Patient dermal fibroblast lines with FAR1 p.Arg480His and p.Arg480Cys","target_id":"node:disorder%3ASpastic_Paraparesis-cataracts-speech_Delay_Syndrome:pathophysiology:Loss%20of%20Plasmalogen-Dependent%20Feedback%20Degradation%20of%20FAR1","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"HIGH","causal_link_type":null,"causal_link_type_label":null,"description":"The HDG challenge is a genuine perturbation experiment rather than an observation: it raises plasmalogen by a route that bypasses FAR1, so the feedback loop is stimulated directly, and the patient cells' failure to respond isolates the regulatory defect from the enzyme's activity.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ASpastic_Paraparesis-cataracts-speech_Delay_Syndrome:0:0","source_id":"node:disorder%3ASpastic_Paraparesis-cataracts-speech_Delay_Syndrome:pathophysiology:De%20Novo%20Heterozygous%20FAR1%20Arg480%20Variant","target_id":"node:disorder%3ASpastic_Paraparesis-cataracts-speech_Delay_Syndrome:pathophysiology:Loss%20of%20Plasmalogen-Dependent%20Feedback%20Degradation%20of%20FAR1","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ASpastic_Paraparesis-cataracts-speech_Delay_Syndrome:1:0","source_id":"node:disorder%3ASpastic_Paraparesis-cataracts-speech_Delay_Syndrome:pathophysiology:Loss%20of%20Plasmalogen-Dependent%20Feedback%20Degradation%20of%20FAR1","target_id":"node:disorder%3ASpastic_Paraparesis-cataracts-speech_Delay_Syndrome:pathophysiology:Elevated%20FAR1%20Protein%20and%20Enzyme%20Activity","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0}]}},{"target":"Uncontrolled Ether Lipid Synthesis","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Spastic_Paraparesis-Cataracts-Speech_Delay_Syndrome.html#pathophysiology-uncontrolled-ether-lipid-synthesis","relationship":"MEASURES","relationship_label":"Measures","fidelity":"HIGH","fidelity_label":"High","description":"The C17:0 labelling experiment measures ether and non-ether lipid synthesis from the same exogenous substrate in the same cells, so the non-ether arm is an internal control for uptake and general lipid handling.","limitations":"A fibroblast's ether lipid demand is not a neuron's or a lens fibre cell's, and the fourfold flux increase measured here cannot be assumed to be the magnitude in the tissues that fail.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0008611","label":"ether lipid biosynthetic process","display_label":"ether lipid biosynthetic process","url":"http://purl.obolibrary.org/obo/GO_0008611"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"C17:0-alcohol incorporation into LPC(O-17:0)","description":null,"target":"Uncontrolled Ether Lipid Synthesis","direction":"INCREASED","interpretation":"Almost fourfold higher in patients, while incorporation into the non-ether LPC(17:0) was unchanged - flux specifically down the ether branch.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:33239752","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33239752","reference_title":"An autosomal dominant neurological disorder caused by de novo variants in FAR1 resulting in uncontrolled synthesis of ether lipids.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Incorporation of C17:0-acid in LPC(17:0) was similar in controls and patients whereas FAR1-dependent incorporation of C17-alcohol in LPC(O-17:0) was almost fourfold higher in patients than in controls","explanation":"The flux measurement underlying this readout, with its internal control."}],"notes":null}],"evidence":[{"reference":"PMID:33239752","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33239752","reference_title":"An autosomal dominant neurological disorder caused by de novo variants in FAR1 resulting in uncontrolled synthesis of ether lipids.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Lipidomic analysis of LPC(17:0) and LPC(O-17:0) was used to compare nonether and ether lipid synthesis, respectively, in fibroblasts of controls and patients.","explanation":"Describes the design that makes this model informative for a flux claim rather than a steady-state one."},{"reference":"PMID:33239752","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33239752","reference_title":"An autosomal dominant neurological disorder caused by de novo variants in FAR1 resulting in uncontrolled synthesis of ether lipids.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Incorporation of C17:0-acid in LPC(17:0) was similar in controls and patients whereas FAR1-dependent incorporation of C17-alcohol in LPC(O-17:0) was almost fourfold higher in patients than in controls","explanation":"The flux measurement underlying this readout, with its internal control."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Spastic_Paraparesis-cataracts-speech_Delay_Syndrome","model_node_id":"model:kb/disorders/Spastic_Paraparesis-cataracts-speech_Delay_Syndrome.yaml:Patient dermal fibroblast lines with FAR1 p.Arg480His and p.Arg480Cys","focus_node_id":"node:disorder%3ASpastic_Paraparesis-cataracts-speech_Delay_Syndrome:pathophysiology:Uncontrolled%20Ether%20Lipid%20Synthesis","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Spastic_Paraparesis-Cataracts-Speech_Delay_Syndrome.html#pathograph","nodes":[{"id":"model:kb/disorders/Spastic_Paraparesis-cataracts-speech_Delay_Syndrome.yaml:Patient dermal fibroblast lines with FAR1 p.Arg480His and p.Arg480Cys","kind":"experimental_model","kind_label":"NAM model","label":"Patient dermal fibroblast lines with FAR1 p.Arg480His and p.Arg480Cys","description":"Skin fibroblasts from patients 1 to 3 (two p.Arg480His, one p.Arg480Cys) against six anonymised control lines. Every functional claim in this entry comes from this model - plasmalogen measurement by gas chromatography, FAR1 enzyme assay, immunoblot, immunofluorescence, the HDG feedback challenge, and lipidomics with C17:0 labelling.\nOn animal models, and the claim needs stating precisely because the obvious reading of it is wrong. There is no animal model of *this* disease and no cell line carrying an engineered Arg480 allele. FAR1 itself is not model-less: a Far1 knockout mouse exists, is subviable with growth retardation and male infertility, and its authors present it as a model of ether lipid *deficiency*. That is the recessive arm, the mechanistic inverse of this disease, and it cannot substitute for a model of Arg480 gain of function.","url":"https://dismech.monarchinitiative.org/pages/disorders/Spastic_Paraparesis-Cataracts-Speech_Delay_Syndrome.html#experimental-model-patient-dermal-fibroblast-lines-with-far1-p-arg480his-and-p-arg480cys","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ASpastic_Paraparesis-cataracts-speech_Delay_Syndrome:pathophysiology:Uncontrolled%20Ether%20Lipid%20Synthesis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Uncontrolled Ether Lipid Synthesis","description":"Flux, not just enzyme level. Feeding fibroblasts a labelled odd-chain fatty acid lets ether and non-ether routes be tracked separately from the same substrate: incorporation into the non-ether lipid LPC(17:0) was the same in patients and controls, while FAR1-dependent incorporation into the ether lipid LPC(O-17:0) was almost fourfold higher in patients. The pathway is running fast, and specifically the ether branch.\nOn the `modifier` value, which is the one interpretive choice in this entry that most needs defending. `GAIN_OF_FUNCTION` is used here, and `INCREASED` is used one node up, deliberately. The schema reserves GAIN_OF_FUNCTION for a process driven outside its normal regulatory constraints rather than merely running above its normal level, and warns against migrating a quantitative annotation to it without that qualitative justification. The justification here is not that ether lipid synthesis is high. It is that the homeostatic loop which sets its level has been eliminated: raising the pathway's own product no longer restrains it, so there is no set point for the output to be above. The authors' own term is \"uncontrolled\". A cell with elevated but still-regulated ether lipid synthesis would be INCREASED; this one has lost the control system.","url":"https://dismech.monarchinitiative.org/pages/disorders/Spastic_Paraparesis-Cataracts-Speech_Delay_Syndrome.html#pathophysiology-uncontrolled-ether-lipid-synthesis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ASpastic_Paraparesis-cataracts-speech_Delay_Syndrome:pathophysiology:Elevated%20FAR1%20Protein%20and%20Enzyme%20Activity","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Elevated FAR1 Protein and Enzyme Activity","description":"The immediate quantitative consequence of the broken brake: more FAR1 protein on immunoblot, and FAR1 enzyme activity in patients' fibroblasts of 379, 323 and 310 pmol per hour per mg protein against control values of 74, 90 and 101 - three to four times control.\nThe `modifier` here is INCREASED, deliberately and in contrast with the node below. The claim at this node is purely quantitative: a normal enzyme, doing its normal reaction, present in larger amounts. Nothing about the enzyme itself is qualitatively altered - immunofluorescence shows normal peroxisomal targeting, and other peroxisomal functions are normal.","url":"https://dismech.monarchinitiative.org/pages/disorders/Spastic_Paraparesis-Cataracts-Speech_Delay_Syndrome.html#pathophysiology-elevated-far1-protein-and-enzyme-activity","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ASpastic_Paraparesis-cataracts-speech_Delay_Syndrome:pathophysiology:Membrane%20Lipid%20Composition%20Shift","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Membrane Lipid Composition Shift","description":"The disease is not simply \"too much plasmalogen\". Lipidomics shows ether species accumulating - plasmanyl/plasmenyl-choline phospholipids, and the neutral ether lipids DG[O] and TG[O] - with a reciprocal and significant fall in the corresponding non-ether phospholipids PC and PE, PE severely. Strikingly, the totals of choline- and ethanolamine-containing lipids stay roughly constant - the paper states this in the same passage, though it cannot be quoted here because the sentence carries the bracketed ether-lipid nomenclature PE[O] and PC[O] that the reference validator strips. What has changed is the ratio of ether to non-ether species, not the amount of membrane phospholipid.\nThe proposed explanation is competition for a shared limited resource - elevated DG[O] outcompeting DG for the activated headgroups CDP-choline and CDP-ethanolamine - which would make this a substrate-competition effect rather than a direct toxicity. The polyunsaturated fatty acids also redistribute, away from PC and toward PC[O].\nRecorded because it is the most plausible bridge from a biochemical abnormality to a cellular one, and because it is the level at which this disease and the RCDP disorders are precise mirror images: in RCDP the non-ether lipids compensate for absent ether counterparts, and the PUFA distribution runs the other way.","url":"https://dismech.monarchinitiative.org/pages/disorders/Spastic_Paraparesis-Cataracts-Speech_Delay_Syndrome.html#pathophysiology-membrane-lipid-composition-shift","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"}],"edges":[{"id":"model-link:1:model:kb/disorders/Spastic_Paraparesis-cataracts-speech_Delay_Syndrome.yaml:Patient dermal fibroblast lines with FAR1 p.Arg480His and p.Arg480Cys","source_id":"model:kb/disorders/Spastic_Paraparesis-cataracts-speech_Delay_Syndrome.yaml:Patient dermal fibroblast lines with FAR1 p.Arg480His and p.Arg480Cys","target_id":"node:disorder%3ASpastic_Paraparesis-cataracts-speech_Delay_Syndrome:pathophysiology:Uncontrolled%20Ether%20Lipid%20Synthesis","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[1]","label":"Measures","directed":false,"relationship":"MEASURES","fidelity":"HIGH","causal_link_type":null,"causal_link_type_label":null,"description":"The C17:0 labelling experiment measures ether and non-ether lipid synthesis from the same exogenous substrate in the same cells, so the non-ether arm is an internal control for uptake and general lipid handling.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ASpastic_Paraparesis-cataracts-speech_Delay_Syndrome:2:0","source_id":"node:disorder%3ASpastic_Paraparesis-cataracts-speech_Delay_Syndrome:pathophysiology:Elevated%20FAR1%20Protein%20and%20Enzyme%20Activity","target_id":"node:disorder%3ASpastic_Paraparesis-cataracts-speech_Delay_Syndrome:pathophysiology:Uncontrolled%20Ether%20Lipid%20Synthesis","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[0]","label":"Directly 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Degradation of FAR1","Uncontrolled Ether Lipid Synthesis"],"relationships":["Recapitulates","Measures"],"fidelities":["High"],"biological_scales":["Molecular","Cellular"],"system_context_sources":["Linked mechanism biological scale"],"modeled_system_labels":["Molecular","Cellular"],"biological_process_terms":[{"id":"GO:0030163","label":"protein catabolic process","display_label":"plasmalogen-triggered degradation of FAR1","url":"http://purl.obolibrary.org/obo/GO_0030163"},{"id":"GO:0008611","label":"ether lipid biosynthetic process","display_label":"ether lipid biosynthetic process","url":"http://purl.obolibrary.org/obo/GO_0008611"}],"biological_processes":["protein catabolic process","ether lipid biosynthetic process"],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":["FAR1 protein level after HDG-induced plasmalogen loading","C17:0-alcohol incorporation into LPC(O-17:0)"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:33239752","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33239752","reference_title":"An autosomal dominant neurological disorder caused by de novo variants in FAR1 resulting in uncontrolled synthesis of ether lipids.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We studied the effect of the identified FAR1 variants in fibroblasts of patients 1-3","explanation":"Establishes which patients the model represents, which bounds what it can be informative about. The same sentence records the alleles as two p.Arg480His and one p.Arg480Cys; that part is not quoted because the source writes the counts in square brackets, which the validator strips."},{"reference":"PMID:33239752","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33239752","reference_title":"An autosomal dominant neurological disorder caused by de novo variants in FAR1 resulting in uncontrolled synthesis of ether lipids.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"In the patients' cells, treatment with HDG also increased C16:0-plasmalogen levels 130-224% (mean ± SD: 160 ± 35%) (Fig. 3c), but this did not result in a consistent decrease of FAR1 protein levels (mean ± SD: 101 ± 17%) (Fig. 3a, b).","explanation":"The measurement underlying this readout, including confirmation that the stimulus worked."},{"reference":"PMID:33239752","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33239752","reference_title":"An autosomal dominant neurological disorder caused by de novo variants in FAR1 resulting in uncontrolled synthesis of ether lipids.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Lipidomic analysis of LPC(17:0) and LPC(O-17:0) was used to compare nonether and ether lipid synthesis, respectively, in fibroblasts of controls and patients.","explanation":"Describes the design that makes this model informative for a flux claim rather than a steady-state one."},{"reference":"PMID:33239752","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33239752","reference_title":"An autosomal dominant neurological disorder caused by de novo variants in FAR1 resulting in uncontrolled synthesis of ether lipids.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Incorporation of C17:0-acid in LPC(17:0) was similar in controls and patients whereas FAR1-dependent incorporation of C17-alcohol in LPC(O-17:0) was almost fourfold higher in patients than in controls","explanation":"The flux measurement underlying this readout, with its internal control."}],"evidence_text":["We studied the effect of the identified FAR1 variants in fibroblasts of patients 1-3","In the patients' cells, treatment with HDG also increased C16:0-plasmalogen levels 130-224% (mean ± SD: 160 ± 35%) (Fig. 3c), but this did not result in a consistent decrease of FAR1 protein levels (mean ± SD: 101 ± 17%) (Fig. 3a, b).","Lipidomic analysis of LPC(17:0) and LPC(O-17:0) was used to compare nonether and ether lipid synthesis, respectively, in fibroblasts of controls and patients.","Incorporation of C17:0-acid in LPC(17:0) was similar in controls and patients whereas FAR1-dependent incorporation of C17-alcohol in LPC(O-17:0) was almost fourfold higher in patients than in controls","Establishes which patients the model represents, which bounds what it can be informative about. The same sentence records the alleles as two p.Arg480His and one p.Arg480Cys; that part is not quoted because the source writes the counts in square brackets, which the validator strips.","The measurement underlying this readout, including confirmation that the stimulus worked.","Describes the design that makes this model informative for a flux claim rather than a steady-state one.","The flux measurement underlying this readout, with its internal control."],"evidence_status":"Evidence recorded","metadata_completeness":30,"metadata_present":["Model category","Modeled mechanism","Evidence"],"metadata_missing":["NAMO class","Organism","Anatomy","Cell type","Cell source","Culture system","Publication"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Spastic_Paraparesis-cataracts-speech_Delay_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Spastic_Paraparesis-cataracts-speech_Delay_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Spastic_Paraparesis-Cataracts-Speech_Delay_Syndrome.html#experimental-model-patient-dermal-fibroblast-lines-with-far1-p-arg480his-and-p-arg480cys","source_anchor":"experimental-model-patient-dermal-fibroblast-lines-with-far1-p-arg480his-and-p-arg480cys"},{"id":"model:kb/disorders/SQSTM1-Related_Childhood-Onset_Neurodegeneration.yaml:Patient dermal fibroblasts","name":"Patient dermal fibroblasts","description":"Fibroblasts from affected individuals in the index cohort, used to confirm absence of p62 protein and to assay the response to mitochondrial depolarisation and autophagosome formation.\n","notes":null,"context_id":"disorder:SQSTM1-Related_Childhood-Onset_Neurodegeneration","context_kind":"Disorder","disease_name":"SQSTM1-Related Childhood-Onset Neurodegeneration","disease_synonyms":["NADGP","neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset","Childhood-onset neurodegeneration with ataxia, dystonia and gaze palsy","Biallelic SQSTM1-related neurodegeneration","p62/sequestosome-1 deficiency"],"disease_term":{"id":"MONDO:0014940","label":"neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset","display_label":"neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset","url":"http://purl.obolibrary.org/obo/MONDO_0014940"},"experimental_model_type":"PRIMARY_CELL_CULTURE","experimental_model_type_label":"Primary-cell culture","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":null,"source_category":"Primary / biopsy-derived","culture_system":null,"publication":"PMID:27545679","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/27545679","mechanisms":[{"target":"Absence of p62/Sequestosome-1 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In one of two siblings the hypertrophy reversed on dichloroacetate, which acts on pyruvate oxidation, consistent with a metabolic rather than fixed structural basis in that patient. Cardiac tissue has not been studied in patients.","url":"https://dismech.monarchinitiative.org/pages/disorders/FBXL4-Related_Mitochondrial_DNA_Depletion_Syndrome.html#pathophysiology-cardiomyocyte-energy-failure","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AFBXL4-Related_Mitochondrial_DNA_Depletion_Syndrome:phenotype:Cataract","kind":"phenotype","kind_label":"Phenotype","label":"Cataract","description":null,"url":"https://dismech.monarchinitiative.org/pages/disorders/FBXL4-Related_Mitochondrial_DNA_Depletion_Syndrome.html#phenotype-cataract","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AFBXL4-Related_Mitochondrial_DNA_Depletion_Syndrome:phenotype:Decreased%20total%20lymphocyte%20count","kind":"phenotype","kind_label":"Phenotype","label":"Decreased total lymphocyte count","description":null,"url":"https://dismech.monarchinitiative.org/pages/disorders/FBXL4-Related_Mitochondrial_DNA_Depletion_Syndrome.html#phenotype-decreased-total-lymphocyte-count","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AFBXL4-Related_Mitochondrial_DNA_Depletion_Syndrome:phenotype:Decreased%20total%20neutrophil%20count","kind":"phenotype","kind_label":"Phenotype","label":"Decreased total neutrophil count","description":null,"url":"https://dismech.monarchinitiative.org/pages/disorders/FBXL4-Related_Mitochondrial_DNA_Depletion_Syndrome.html#phenotype-decreased-total-neutrophil-count","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AFBXL4-Related_Mitochondrial_DNA_Depletion_Syndrome:phenotype:Elevated%20circulating%20hepatic%20transaminase%20concentration","kind":"phenotype","kind_label":"Phenotype","label":"Elevated circulating hepatic transaminase concentration","description":"Mildly elevated transaminases.","url":"https://dismech.monarchinitiative.org/pages/disorders/FBXL4-Related_Mitochondrial_DNA_Depletion_Syndrome.html#phenotype-elevated-circulating-hepatic-transaminase-concentration","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AFBXL4-Related_Mitochondrial_DNA_Depletion_Syndrome:phenotype:Gastrointestinal%20dysmotility","kind":"phenotype","kind_label":"Phenotype","label":"Gastrointestinal dysmotility","description":null,"url":"https://dismech.monarchinitiative.org/pages/disorders/FBXL4-Related_Mitochondrial_DNA_Depletion_Syndrome.html#phenotype-gastrointestinal-dysmotility","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AFBXL4-Related_Mitochondrial_DNA_Depletion_Syndrome:pathophysiology:Impaired%20Anaplerosis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Anaplerosis","description":"In two siblings who presented with neonatal hyperammonemia, low plasma aspartate and low urinary TCA cycle intermediates suggested a failure to replenish TCA cycle intermediates; the authors propose this as the basis of the hyperammonemia and suggest anaplerotic therapy. This has not been tested in other patients or in a model.","url":"https://dismech.monarchinitiative.org/pages/disorders/FBXL4-Related_Mitochondrial_DNA_Depletion_Syndrome.html#pathophysiology-impaired-anaplerosis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"HYPOTHETICAL","mechanism_confidence_label":"Hypothetical"},{"id":"node:disorder%3AFBXL4-Related_Mitochondrial_DNA_Depletion_Syndrome:phenotype:Lactic%20acidosis","kind":"phenotype","kind_label":"Phenotype","label":"Lactic acidosis","description":"Congenital or neonatal persistent lactic acidosis with metabolic acidosis; the most consistent finding and part of the presenting pattern. Episodic exacerbations accompany intercurrent illness.","url":"https://dismech.monarchinitiative.org/pages/disorders/FBXL4-Related_Mitochondrial_DNA_Depletion_Syndrome.html#phenotype-lactic-acidosis","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AFBXL4-Related_Mitochondrial_DNA_Depletion_Syndrome:pathophysiology:Mitochondrial%20DNA%20Depletion","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Mitochondrial DNA Depletion","description":"Reduced mtDNA copy number, severe in skeletal muscle and milder or absent in cultured fibroblasts; one fibroblast line with a homozygous truncating variant had normal copy number.","url":"https://dismech.monarchinitiative.org/pages/disorders/FBXL4-Related_Mitochondrial_DNA_Depletion_Syndrome.html#pathophysiology-mitochondrial-dna-depletion","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AFBXL4-Related_Mitochondrial_DNA_Depletion_Syndrome:pathophysiology:Mitochondrial%20Myopathy","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Mitochondrial Myopathy","description":"Skeletal muscle shows severe mtDNA depletion, a paucity of mitochondria with ultrastructural abnormalities and a combined respiratory chain deficiency; creatine kinase is intermittently raised.","url":"https://dismech.monarchinitiative.org/pages/disorders/FBXL4-Related_Mitochondrial_DNA_Depletion_Syndrome.html#pathophysiology-mitochondrial-myopathy","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AFBXL4-Related_Mitochondrial_DNA_Depletion_Syndrome:pathophysiology:Neuronal%20Energy%20Failure","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Neuronal Energy Failure","description":"Energy failure in neurons, presumed from the brain phenotype. Excess mitophagy is shown in cortical neurons derived from patient iPSCs, but neuronal bioenergetics and neuron loss have not been measured in patient brain. Imaging shows a rapidly progressive brain atrophy after nonspecific neonatal findings, and destructive brain changes can begin before birth.","url":"https://dismech.monarchinitiative.org/pages/disorders/FBXL4-Related_Mitochondrial_DNA_Depletion_Syndrome.html#pathophysiology-neuronal-energy-failure","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AFBXL4-Related_Mitochondrial_DNA_Depletion_Syndrome:pathophysiology:Reduced%20Mitochondrial%20Content","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced Mitochondrial Content","description":"Fewer mitochondria per cell, with a global fall in mitochondrial proteins and a rise in lysosomal proteins. In the knockout mouse and in human knockout cells the remaining mitochondria are functional; the deficit is one of number. 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Pharmacological inhibition partially restores the mutant RNA.","Publisher full text of Pavinato et al., Brain 2023, PMID:35979925: CAPRIN1 haploinsufficiency causes a neurodevelopmental disorder with language impairment, ADHD and ASD. 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After this treatment, allelic balance on RNA level could be nearly restored back to normal, as proven by pyrosequencing.","explanation":"Puromycin rescue of allelic RNA imbalance supports nonsense-mediated decay in the deep-intronic family."},{"reference":"PMID:28442211","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/28442211","reference_title":"Leigh-like neuroimaging features associated with new biallelic mutations in OPA1.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We also observed in patients' fibroblasts a higher proportion of fragmented and intermediate mitochondria upon galactose treatment compared to controls","explanation":"Network morphology is measured directly; impaired fusion is the mechanistic interpretation."},{"reference":"PMID:28494813","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/28494813","reference_title":"Not only dominant, not only optic atrophy: expanding the clinical spectrum associated with OPA1 mutations.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The ATP content in P3 fi- broblasts was normal respect to controls in regular medium but significantly reduced in galactose medium reflecting the lower efficiency of ATP production by OXPHOS in stress condition","explanation":"Homozygous Ala394Thr fibroblasts show a stress-dependent ATP defect; it is not a universal resting ATP deficiency."}],"evidence_text":["To suppress nonsense-mediated messenger RNA decay-dependent allelic decay we used puromycin treatment in patient derived fibroblasts. After this treatment, allelic balance on RNA level could be nearly restored back to normal, as proven by pyrosequencing.","We also observed in patients' fibroblasts a higher proportion of fragmented and intermediate mitochondria upon galactose treatment compared to controls","The ATP content in P3 fi- broblasts was normal respect to controls in regular medium but significantly reduced in galactose medium reflecting the lower efficiency of ATP production by OXPHOS in stress condition","Puromycin rescue of allelic RNA imbalance supports nonsense-mediated decay in the deep-intronic family.","Network morphology is measured directly; impaired fusion is the mechanistic interpretation.","Homozygous Ala394Thr fibroblasts show a stress-dependent ATP defect; it is not a universal resting ATP deficiency."],"evidence_status":"Evidence recorded","metadata_completeness":40,"metadata_present":["Model category","Organism","Modeled mechanism","Evidence"],"metadata_missing":["NAMO class","Anatomy","Cell type","Cell source","Culture system","Publication"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Behr_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Behr_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Behr_Syndrome.html#experimental-model-patient-fibroblasts-with-biallelic-opa1-variants","source_anchor":"experimental-model-patient-fibroblasts-with-biallelic-opa1-variants"},{"id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_39.yaml:Patient fibroblasts with wild-type NDUFB7 complementation","name":"Patient fibroblasts with wild-type NDUFB7 complementation","description":"Skin fibroblasts from the index patient, carrying the homozygous intronic variant, in which complex I activity was measured before and after expression of wild-type NDUFB7. 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It tests the candidate gene against the biochemical phenotype inside the patient's own genetic background, so it is not vulnerable to the objection that some other variant in that genome caused the enzyme defect.","limitations":"Fibroblasts, not heart or brain, so nothing about tissue selectivity or about the cardiomyopathy is testable here. The rescue also establishes that NDUFB7 is limiting for complex I activity in these cells, not the assembly-level mechanism by which it is limiting; no complexome profile or assembly-intermediate analysis has been reported for this patient.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[],"biological_processes":[],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Complex I enzymatic activity in patient fibroblasts","description":null,"target":"Isolated Complex I Enzyme Deficiency","direction":"RESTORED","interpretation":"Reduced in the patient line and normalised by expression of wild-type NDUFB7, which is the direct causal link between gene and biochemical phenotype.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:33502047","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33502047","reference_title":"Severe congenital lactic acidosis and hypertrophic cardiomyopathy caused by an intronic variant in NDUFB7.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Complementation studies with expression of wild-type NDUFB7 in patient fibroblasts normalized complex I function.","explanation":"The rescue measurement this readout records."}],"notes":null}],"evidence":[{"reference":"PMID:33502047","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33502047","reference_title":"Severe congenital lactic acidosis and hypertrophic cardiomyopathy caused by an intronic variant in NDUFB7.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The detected variant resulted in a significant reduction of the NDUFB7 protein and reduced complex I activity.","explanation":"The baseline defect in the same cells, without which the rescue would have nothing to restore."},{"reference":"PMID:33502047","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33502047","reference_title":"Severe congenital lactic acidosis and hypertrophic cardiomyopathy caused by an intronic variant in NDUFB7.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Complementation studies with expression of wild-type NDUFB7 in patient fibroblasts normalized complex I function.","explanation":"The rescue measurement this readout records."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Mitochondrial_Complex_I_Deficiency_Nuclear_Type_39","model_node_id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_39.yaml:Patient fibroblasts with wild-type NDUFB7 complementation","focus_node_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_39:pathophysiology:Isolated%20Complex%20I%20Enzyme%20Deficiency","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_39.html#pathograph","nodes":[{"id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_39.yaml:Patient fibroblasts with wild-type NDUFB7 complementation","kind":"experimental_model","kind_label":"NAM model","label":"Patient fibroblasts with wild-type NDUFB7 complementation","description":"Skin fibroblasts from the index patient, carrying the homozygous intronic variant, in which complex I activity was measured before and after expression of wild-type NDUFB7. 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This node is where the causal argument closes: expressing wild-type NDUFB7 in the patient's own fibroblasts normalised complex I function, so the enzyme defect is attributable to NDUFB7 and not to an unrelated variant carried by the same patient.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_39.html#pathophysiology-isolated-complex-i-enzyme-deficiency","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_39:pathophysiology:Bioenergetic%20Failure%20in%20High-Demand%20Tissues","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Bioenergetic Failure in High-Demand Tissues","description":"Reduced electron transfer through complex I lowers oxidative phosphorylation output, and the tissues that decompensate first are the ones with the highest ATP demand: heart and brain. The clinical picture in the index patient follows that pattern, with hypertrophic cardiomyopathy and encephalopathy, and the anaerobic compensation shows as lactic acidosis.\nThe tissue-selectivity reasoning is standard mitochondrial-medicine inference rather than a measurement in this patient, so the node is marked PROVISIONAL. No cardiac or brain tissue enzymology was reported.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_39.html#pathophysiology-bioenergetic-failure-in-high-demand-tissues","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_39:pathophysiology:Destabilised%20Assembly%20of%20the%20Complex%20I%20Membrane%20Arm","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Destabilised Assembly of the Complex I Membrane Arm","description":"The step from a missing subunit to a broken enzyme. A systematic knockout screen of every accessory subunit found that losing any one of them destabilises the other subunits sitting in the same structural module, and that twenty-five of the thirty-one are strictly required for a functional complex to assemble at all.\nThat is the mechanism this node asserts, and it is asserted as a general property of accessory subunits rather than as a measurement on NDUFB7. The cached record of the screen reports the rule across subunits without naming NDUFB7's module or its individual result, and no complexome profile has been published for a MC1DN39 patient. The node is marked PROVISIONAL for that reason.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_39.html#pathophysiology-destabilised-assembly-of-the-complex-i-membrane-arm","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"}],"edges":[{"id":"model-link:0:model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_39.yaml:Patient fibroblasts with wild-type NDUFB7 complementation","source_id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_39.yaml:Patient fibroblasts with wild-type NDUFB7 complementation","target_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_39:pathophysiology:Isolated%20Complex%20I%20Enzyme%20Deficiency","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Rescues","directed":false,"relationship":"RESCUES","fidelity":"HIGH","causal_link_type":null,"causal_link_type_label":null,"description":"The complementation arm is the causality argument for this disease. 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Asp175Asn","focus_node_id":"node:disorder%3AHypertrophic_Cardiomyopathy_3:pathophysiology:Cardiomyocyte%20Hypercontractility%20and%20Impaired%20Relaxation","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_3.html#pathograph","nodes":[{"id":"model:kb/disorders/Hypertrophic_Cardiomyopathy_3.yaml:Patient hiPSC-derived cardiomyocytes carrying TPM1 Asp175Asn","kind":"experimental_model","kind_label":"NAM model","label":"Patient hiPSC-derived cardiomyocytes carrying TPM1 Asp175Asn","description":"Human induced pluripotent stem cell-derived cardiomyocytes from a carrier of the founding CMH3 allele Asp175Asn, compared side by side with MYBPC3-Gln1061X cardiomyocytes to test whether thin- and thick-filament HCM differ at the cellular 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cellular hypertrophy. Patient-derived hiPSC-cardiomyocytes carrying the classic Asp175Asn allele reproduce the cellular phenotype with increased cell size and altered calcium handling and electrophysiology. Hypercontractility is the pathophysiological abnormality that myosin-inhibitor therapy is designed to reverse.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_3.html#pathophysiology-cardiomyocyte-hypercontractility-and-impaired-relaxation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_3:pathophysiology:Cardiomyocyte%20Hypertrophy%20with%20Myofiber%20Disarray%20and%20Interstitial%20Fibrosis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Cardiomyocyte Hypertrophy with Myofiber Disarray and Interstitial Fibrosis","description":"Sustained hypercontractility and calcium-dependent hypertrophic signaling remodel the myocardium into the classic hypertrophic pattern: myocyte hypertrophy, loss of the normal parallel myofibre architecture (disarray), and replacement/interstitial fibrosis, producing wall thickening with a small cavity. Histology in TPM1-mutation hearts is indistinguishable from that of other sarcomeric causes, so the node is a faithful specialization of the generic ventricular-remodeling node rather than a TPM1-specific pathology. Human cardiac biopsies carrying TPM1 variants show loss of sarcomeric structure.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_3.html#pathophysiology-cardiomyocyte-hypertrophy-with-myofiber-disarray-and-interstitial-fibrosis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_3:pathophysiology:Diastolic%20Dysfunction%20and%20Left%20Ventricular%20Outflow%20Tract%20Obstruction","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Diastolic Dysfunction and Left Ventricular Outflow Tract Obstruction","description":"The stiffened, hypertrophied, fibrotic ventricle fills poorly, and when hypertrophy is asymmetric and septal it can also obstruct the left ventricular outflow tract dynamically. The clinical result is exertional dyspnoea, chest pain, and reduced exercise capacity with preserved or supranormal ejection fraction. Thin-filament HCM as a class tends to produce relatively less hypertrophy and less outflow obstruction than thick-filament HCM while carrying more heart-failure morbidity, so the obstructive presentation should not be assumed in a TPM1 carrier.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_3.html#pathophysiology-diastolic-dysfunction-and-left-ventricular-outflow-tract-obstruction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_3:pathophysiology:Loss%20of%20Crossbridge%20Inhibition%20and%20Increased%20Myofilament%20Calcium%20Sensitivity","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Loss of Crossbridge Inhibition and Increased Myofilament Calcium Sensitivity","description":"Mutant alpha-tropomyosin is more flexible and sits less stably in the inhibitory (blocked/closed) position on actin, so the thin filament fails to keep myosin switched off. The measurable consequences are a left-shift in the calcium dependence of filament sliding, residual actomyosin activity at low calcium, and loss of the normal inhibition of sliding in relaxing conditions. Different alleles reach this end state by different routes - S215L and D219V principally by destabilizing the blocked state, E192K by permitting residual crossbridge activity even while overall calcium sensitivity falls - which is why calcium sensitivity alone is an incomplete description of the lesion.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_3.html#pathophysiology-loss-of-crossbridge-inhibition-and-increased-myofilament-calcium-sensitivity","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Hypertrophic_Cardiomyopathy_3.yaml:Patient hiPSC-derived cardiomyocytes carrying TPM1 Asp175Asn","source_id":"model:kb/disorders/Hypertrophic_Cardiomyopathy_3.yaml:Patient hiPSC-derived cardiomyocytes carrying TPM1 Asp175Asn","target_id":"node:disorder%3AHypertrophic_Cardiomyopathy_3:pathophysiology:Cardiomyocyte%20Hypercontractility%20and%20Impaired%20Relaxation","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Not 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causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":null,"intermediate_mechanisms":[],"hypothesis_groups":["tpm1_loss_of_crossbridge_inhibition"],"evidence_count":0}]}}],"mechanism_names":["Cardiomyocyte Hypercontractility and Impaired Relaxation"],"relationships":["Not Specified"],"fidelities":["Not Specified"],"biological_scales":["Cellular"],"system_context_sources":["Model-level cell type","Linked mechanism cell type","Linked mechanism biological scale"],"modeled_system_labels":["cardiac muscle cell","Cellular"],"biological_process_terms":[{"id":"GO:0060048","label":"cardiac muscle contraction","display_label":"Cardiac muscle contraction","url":"http://purl.obolibrary.org/obo/GO_0060048"},{"id":"GO:0055119","label":"relaxation of cardiac muscle","display_label":"Relaxation of cardiac muscle","url":"http://purl.obolibrary.org/obo/GO_0055119"}],"biological_processes":["cardiac muscle contraction","relaxation of cardiac muscle"],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":[],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[{"statement":"Pathological HCM phenotype with cellular enlargement, altered calcium handling and electrophysiology, and a gene-expression profile distinct from the thick-filament comparator.","evidence":[]}],"findings_text":["Pathological HCM phenotype with cellular enlargement, altered calcium handling and electrophysiology, and a gene-expression profile distinct from the thick-filament comparator."],"evidence":[{"reference":"PMID:27057166","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/27057166","reference_title":"Mutation-Specific Phenotypes in hiPSC-Derived Cardiomyocytes Carrying Either Myosin-Binding Protein C Or alpha-Tropomyosin Mutation for Hypertrophic Cardiomyopathy.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Both types of HCM-CMs displayed pathological phenotype of HCM but, more importantly, we found differences between CMs carrying either MYBPC3-Gln1061X or TPM1-Asp175Asn gene mutation in their cellular size, Ca(2+) handling, and electrophysiological properties, as well as their gene expression profiles.","explanation":"Describes the model and the mutation-specific result."}],"evidence_text":["Both types of HCM-CMs displayed pathological phenotype of HCM but, more importantly, we found differences between CMs carrying either MYBPC3-Gln1061X or TPM1-Asp175Asn gene mutation in their cellular size, Ca(2+) handling, and electrophysiological properties, as well as their gene expression profiles.","Describes the model and the mutation-specific result."],"evidence_status":"Evidence recorded","metadata_completeness":60,"metadata_present":["Model category","Organism","Cell type","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Anatomy","Cell source","Culture system"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Hypertrophic_Cardiomyopathy_3.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hypertrophic_Cardiomyopathy_3.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_3.html#experimental-model-patient-hipsc-derived-cardiomyocytes-carrying-tpm1-asp175asn","source_anchor":"experimental-model-patient-hipsc-derived-cardiomyocytes-carrying-tpm1-asp175asn"},{"id":"model:kb/disorders/SQSTM1-Related_Childhood-Onset_Neurodegeneration.yaml:Patient iPSC line IGIBi010-A","name":"Patient iPSC line IGIBi010-A","description":"An induced pluripotent stem cell line derived from a patient homozygous for the p.Leu251SerfsTer4 frameshift allele. It is a resource rather than a completed experiment: no disease phenotype has yet been reported from it.\n","notes":null,"context_id":"disorder:SQSTM1-Related_Childhood-Onset_Neurodegeneration","context_kind":"Disorder","disease_name":"SQSTM1-Related Childhood-Onset Neurodegeneration","disease_synonyms":["NADGP","neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset","Childhood-onset neurodegeneration with ataxia, dystonia and gaze palsy","Biallelic SQSTM1-related neurodegeneration","p62/sequestosome-1 deficiency"],"disease_term":{"id":"MONDO:0014940","label":"neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset","display_label":"neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset","url":"http://purl.obolibrary.org/obo/MONDO_0014940"},"experimental_model_type":"IPSC_DERIVED_MODEL","experimental_model_type_label":"iPSC-derived model","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":null,"source_category":"iPSC-derived","culture_system":null,"publication":"PMID:39126919","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39126919","mechanisms":[{"target":"Absence of p62/Sequestosome-1 Protein","target_url":"https://dismech.monarchinitiative.org/pages/disorders/SQSTM1-Related_Childhood-Onset_Neurodegeneration.html#pathophysiology-absence-of-p62-sequestosome-1-protein","relationship":"MEASURES","relationship_label":"Measures","fidelity":"UNKNOWN","fidelity_label":"Unknown","description":"Carries a patient null genotype and is available for differentiation into disease-relevant neuronal lineages.","limitations":"A characterised line only. No differentiated phenotype, no isogenic control comparison and no functional result have been published, so it cannot yet support a mechanistic claim.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[],"biological_processes":[],"pathways":[],"genes":[],"chemicals":[],"readouts":[],"evidence":[{"reference":"PMID:39126919","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39126919","reference_title":"Generation and characterization of human-derived induced pluripotent stem cell line (IGIBi010-A) from a patient with neurodegenerative disease phenotype carrying mutation in SQSTM1/p62 gene.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We report here, the generation of induced pluripotent stem cell (iPSC) line (IGIBi010-A) carrying a novel homozygous frameshift variant in SQSTM1 i.e. p.Leu251SerfsTer4.","explanation":"Establishes the existence and genotype of the patient-derived line."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:SQSTM1-Related_Childhood-Onset_Neurodegeneration","model_node_id":"model:kb/disorders/SQSTM1-Related_Childhood-Onset_Neurodegeneration.yaml:Patient iPSC line IGIBi010-A","focus_node_id":"node:disorder%3ASQSTM1-Related_Childhood-Onset_Neurodegeneration:pathophysiology:Absence%20of%20p62%2FSequestosome-1%20Protein","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/SQSTM1-Related_Childhood-Onset_Neurodegeneration.html#pathograph","nodes":[{"id":"model:kb/disorders/SQSTM1-Related_Childhood-Onset_Neurodegeneration.yaml:Patient iPSC line IGIBi010-A","kind":"experimental_model","kind_label":"NAM model","label":"Patient iPSC line IGIBi010-A","description":"An induced pluripotent stem cell line derived from a patient homozygous for the p.Leu251SerfsTer4 frameshift allele. It is a resource rather than a completed experiment: no disease phenotype has yet been reported from it.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/SQSTM1-Related_Childhood-Onset_Neurodegeneration.html#experimental-model-patient-ipsc-line-igibi010-a","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ASQSTM1-Related_Childhood-Onset_Neurodegeneration:pathophysiology:Absence%20of%20p62%2FSequestosome-1%20Protein","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Absence of p62/Sequestosome-1 Protein","description":"p62 protein is undetectable in patient cells. This is a complete-absence state rather than an altered-function state, which is the molecular distinction from the dominant SQSTM1 disorders, where a missense p62 is present but behaves abnormally.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/SQSTM1-Related_Childhood-Onset_Neurodegeneration.html#pathophysiology-absence-of-p62-sequestosome-1-protein","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ASQSTM1-Related_Childhood-Onset_Neurodegeneration:pathophysiology:Biallelic%20SQSTM1%20Loss-of-Function","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Biallelic SQSTM1 Loss-of-Function","description":"Two null SQSTM1 alleles — nonsense, frameshift, canonical-splice, start-loss, or a synonymous change that disrupts splicing — are inherited from carrier parents. The resulting transcripts are degraded or encode truncated, non-functional protein.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/SQSTM1-Related_Childhood-Onset_Neurodegeneration.html#pathophysiology-biallelic-sqstm1-loss-of-function","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ASQSTM1-Related_Childhood-Onset_Neurodegeneration:pathophysiology:Blunted%20KEAP1-NRF2%20Antioxidant%20Response","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Blunted KEAP1-NRF2 Antioxidant Response","description":"p62's KEAP1-interacting region normally competes with NRF2 for the KEAP1 binding site, so p62 stabilises NRF2 and sustains antioxidant gene transcription. Complete p62 loss is therefore predicted to leave NRF2 less protected from KEAP1-directed degradation and the antioxidant response blunted. This node is an inference from the inverse experiment (p62 overproduction stabilises NRF2); it has not been measured in NADGP patients or patient cells, and is scoped to a hypothesis group for that reason.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/SQSTM1-Related_Childhood-Onset_Neurodegeneration.html#pathophysiology-blunted-keap1-nrf2-antioxidant-response","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ASQSTM1-Related_Childhood-Onset_Neurodegeneration:pathophysiology:Failure%20of%20Selective%20Autophagy%20Cargo%20Recognition","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Failure of Selective Autophagy Cargo Recognition","description":"Without p62 the cell cannot polymerise ubiquitinated cargo into sequestration-competent bodies or hand them to LC3 on the phagophore. Patient and knockout cells fail to form ubiquitin-positive aggregates under misfolded-protein stress and autophagic flux slows. Note that this is a cargo-recognition lesion, not a defect of the core autophagy machinery: the autophagosome can still be built, but selectively loading it fails.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/SQSTM1-Related_Childhood-Onset_Neurodegeneration.html#pathophysiology-failure-of-selective-autophagy-cargo-recognition","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/SQSTM1-Related_Childhood-Onset_Neurodegeneration.yaml:Patient iPSC line IGIBi010-A","source_id":"model:kb/disorders/SQSTM1-Related_Childhood-Onset_Neurodegeneration.yaml:Patient iPSC line IGIBi010-A","target_id":"node:disorder%3ASQSTM1-Related_Childhood-Onset_Neurodegeneration:pathophysiology:Absence%20of%20p62%2FSequestosome-1%20Protein","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Measures","directed":false,"relationship":"MEASURES","fidelity":"UNKNOWN","causal_link_type":null,"causal_link_type_label":null,"description":"Carries a patient null genotype and is available for differentiation into disease-relevant neuronal lineages.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ASQSTM1-Related_Childhood-Onset_Neurodegeneration:1:1","source_id":"node:disorder%3ASQSTM1-Related_Childhood-Onset_Neurodegeneration:pathophysiology:Absence%20of%20p62%2FSequestosome-1%20Protein","target_id":"node:disorder%3ASQSTM1-Related_Childhood-Onset_Neurodegeneration:pathophysiology:Blunted%20KEAP1-NRF2%20Antioxidant%20Response","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[1]","label":"Indirectly causes (known intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_KNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Known Intermediates","description":"p62 also competes with NRF2 for the same binding site on KEAP1. 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This is the metabolic insult that the conserved peripheral-axonal-degeneration module describes generically; here it is the whole trigger, with no toxic, inflammatory or hyperglycaemic component.","url":"https://dismech.monarchinitiative.org/pages/disorders/Sorbitol_Dehydrogenase_Deficiency.html#pathophysiology-polyol-pathway-block-with-sorbitol-accumulation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ASorbitol_Dehydrogenase_Deficiency:pathophysiology:Distal%20Motor%20Axonal%20Degeneration%20and%20Demyelination","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Distal Motor Axonal Degeneration and Demyelination","description":"Degeneration falls on myelinated motor axons and largely spares myelinated sensory axons - the structural counterpart of the motor-predominant clinical picture. 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Human sural nerve, sampled in a sensory nerve in a motor-predominant disease, shows correspondingly mild change: modest loss of large myelinated fibres with a few thinly myelinated fibres.","url":"https://dismech.monarchinitiative.org/pages/disorders/Sorbitol_Dehydrogenase_Deficiency.html#pathophysiology-distal-motor-axonal-degeneration-and-demyelination","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ASorbitol_Dehydrogenase_Deficiency:pathophysiology:Loss%20of%20Sorbitol%20Dehydrogenase%20Activity","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Loss of Sorbitol Dehydrogenase Activity","description":"Sorbitol dehydrogenase (EC 1.1.1.14), the NAD+-dependent second enzyme of the polyol pathway, is absent from patient cells. 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The 30% figure quoted in the biochemical record is that assay's proposed cutoff, not a measured residual activity of the disease.","url":"https://dismech.monarchinitiative.org/pages/disorders/Sorbitol_Dehydrogenase_Deficiency.html#pathophysiology-loss-of-sorbitol-dehydrogenase-activity","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ASorbitol_Dehydrogenase_Deficiency:pathophysiology:Mitochondrial%20Dysfunction%20and%20Oxidative%20Stress","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Mitochondrial Dysfunction and Oxidative Stress","description":"Sord-deficient Drosophila show reduced brain ATP production and reactive oxygen species accumulation in CNS and muscle, and both are corrected by aldose reductase inhibition, which ties them to sorbitol rather than to the genotype in general. Independent human support comes from proteomic analysis of patient skeletal muscle, where respiratory complex I deficiency dominated and the malate/oxaloacetate ratio was raised. The node is marked PROVISIONAL because the animal evidence is invertebrate and the human evidence is muscle proteomics rather than nerve.","url":"https://dismech.monarchinitiative.org/pages/disorders/Sorbitol_Dehydrogenase_Deficiency.html#pathophysiology-mitochondrial-dysfunction-and-oxidative-stress","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ASorbitol_Dehydrogenase_Deficiency:pathophysiology:Osmotic%20Stress%20in%20Schwann%20Cells%20and%20Myelinated%20Axons","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Osmotic Stress in Schwann Cells and Myelinated Axons","description":"The osmotic candidate for how a trapped metabolite injures nerve. 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This is the convergence point of the disease: whatever the subunit and whichever phase of the viral life cycle, the cell fails to hold the virus down, and everything downstream is a consequence of uncontrolled VZV in a particular tissue.","url":"https://dismech.monarchinitiative.org/pages/disorders/Immunodeficiency_101_Varicella_Zoster_Virus-Specific.html#pathophysiology-failure-to-restrict-vzv-replication","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AImmunodeficiency_101_Varicella_Zoster_Virus-specific:pathophysiology:Impaired%20Cytosolic%20Sensing%20of%20AT-Rich%20VZV%20DNA","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Cytosolic Sensing of AT-Rich VZV DNA","description":"RNA polymerase III has a second job beyond housekeeping transcription: in the cytosol it transcribes AT-rich double-stranded DNA into 5'-triphosphate RNA, which is a ligand for RIG-I and thus a trigger for type I interferon. This node is the failure of that recognition step. It is also the best available explanation for the disease's most striking feature — that the susceptibility is confined to one virus. VZV has an AT-rich genome, so it is the pathogen most dependent on this particular sensing route; patients do not have increased susceptibility to other infections.","url":"https://dismech.monarchinitiative.org/pages/disorders/Immunodeficiency_101_Varicella_Zoster_Virus-Specific.html#pathophysiology-impaired-cytosolic-sensing-of-at-rich-vzv-dna","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Immunodeficiency_101_Varicella_Zoster_Virus-specific.yaml:Patient peripheral blood mononuclear cells with wild-type allele rescue","source_id":"model:kb/disorders/Immunodeficiency_101_Varicella_Zoster_Virus-specific.yaml:Patient peripheral blood mononuclear cells with wild-type allele 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infections.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Leukocytes from all 4 patients tested exhibited poor IFN induction in response to synthetic or VZV-derived DNA.","explanation":"Reports the direction and the stimuli."},{"reference":"PMID:28783042","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/28783042","reference_title":"Inborn errors in RNA polymerase III underlie severe varicella zoster virus infections.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"These phenotypes were rescued by transduction with relevant WT alleles.","explanation":"Reports the rescue result."}],"evidence_text":["confer increased susceptibility to severe VZV disease in otherwise healthy children, providing evidence for an essential role of a DNA sensor in human immunity","Leukocytes from all 4 patients tested exhibited poor IFN induction in response to synthetic or VZV-derived DNA.","These phenotypes were rescued by transduction with relevant WT alleles.","The authors frame the patient-cell work as evidence for an essential role of a DNA sensor in human immunity, which is what this model measures.","Reports the direction and the stimuli.","Reports the rescue result."],"evidence_status":"Evidence recorded","metadata_completeness":40,"metadata_present":["Model category","Cell type","Modeled mechanism","Evidence"],"metadata_missing":["NAMO class","Organism","Anatomy","Cell source","Culture system","Publication"],"dataset_context":"None recorded in same 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Normal oligomycin-sensitive ATPase activity in both fibroblast preparations and P2 muscle contrasts with the earlier cybrid result. P2 had no significant JC1 membrane-potential or ATP6-expression decrease. Complex V subcomplexes do not settle assembly versus catalytic mechanisms; neuronal tissue and adult onset were not modeled.","context_id":"disorder:Adult-Onset_Ataxia_and_Polyneuropathy","context_kind":"Disorder","disease_name":"Adult-Onset Ataxia and Polyneuropathy","disease_synonyms":["Ataxia and polyneuropathy, adult-onset","Adult-onset MT-ATP6 ataxia and axonal neuropathy"],"disease_term":{"id":"MONDO:0010781","label":"ataxia and polyneuropathy, adult-onset","display_label":"adult-onset ataxia and polyneuropathy","url":"http://purl.obolibrary.org/obo/MONDO_0010781"},"experimental_model_type":"PRIMARY_CELL_CULTURE","experimental_model_type_label":"Primary-cell culture","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":"Cultured skin fibroblasts from a toddler and a 19-year-old with homoplasmic m.9035T>C underwent Seahorse respiratory testing, ATPase assays and native-gel analysis.","source_category":"Primary / biopsy-derived","culture_system":null,"publication":"PMID:35159298","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35159298","mechanisms":[{"target":"Impaired ATP Synthase Function","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Adult-Onset_Ataxia_and_Polyneuropathy.html#pathophysiology-impaired-atp-synthase-function","relationship":"PARTIALLY_RECAPITULATES","relationship_label":"Partially Recapitulates","fidelity":"LOW","fidelity_label":"Low","description":"Assay-specific evidence for mitochondrial dysfunction.","limitations":"Two patient donors, mixed-age controls and assay-dependent abnormalities. Normal oligomycin-sensitive ATPase activity in both fibroblast preparations and P2 muscle contrasts with the earlier cybrid result. P2 had no significant JC1 membrane-potential or ATP6-expression decrease. Complex V subcomplexes do not settle assembly versus catalytic mechanisms; neuronal tissue and adult onset were not modeled.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0015986","label":"proton motive force-driven ATP synthesis","display_label":"proton motive force-driven ATP synthesis","url":"http://purl.obolibrary.org/obo/GO_0015986"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[],"evidence":[{"reference":"PMID:35159298","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/35159298","reference_title":"Clinical Heterogeneity in MT-ATP6 Pathogenic Variants: Same Genotype-Different Onset.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Bioenergetic measurements in fibroblasts from both patients detected reduced spare respiratory capacities and altered extracellular acidification rates, revealing a switch from mitochondrial respiration to glycolysis to uphold ATP production.","explanation":"Primary fibroblast assays, with differing magnitude and normalization dependence across the two donors."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Adult-Onset_Ataxia_and_Polyneuropathy","model_node_id":"model:kb/disorders/Adult-Onset_Ataxia_and_Polyneuropathy.yaml:Patient primary fibroblasts with homoplasmic m.9035T>C","focus_node_id":"node:disorder%3AAdult-Onset_Ataxia_and_Polyneuropathy:pathophysiology:Impaired%20ATP%20Synthase%20Function","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Adult-Onset_Ataxia_and_Polyneuropathy.html#pathograph","nodes":[{"id":"model:kb/disorders/Adult-Onset_Ataxia_and_Polyneuropathy.yaml:Patient primary fibroblasts with homoplasmic m.9035T>C","kind":"experimental_model","kind_label":"NAM model","label":"Patient primary fibroblasts with homoplasmic m.9035T>C","description":"Cultured skin fibroblasts from a toddler and a 19-year-old with homoplasmic m.9035T>C underwent Seahorse respiratory testing, ATPase assays and native-gel analysis.","url":"https://dismech.monarchinitiative.org/pages/disorders/Adult-Onset_Ataxia_and_Polyneuropathy.html#experimental-model-patient-primary-fibroblasts-with-homoplasmic-m-9035t-c","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAdult-Onset_Ataxia_and_Polyneuropathy:pathophysiology:Impaired%20ATP%20Synthase%20Function","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired ATP Synthase Function","description":"The m.8993T>C ATP6 substitution perturbs ATP-synthase-related bioenergetics. 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The assays and cellular backgrounds differ.","url":"https://dismech.monarchinitiative.org/pages/disorders/Adult-Onset_Ataxia_and_Polyneuropathy.html#pathophysiology-impaired-atp-synthase-function","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAdult-Onset_Ataxia_and_Polyneuropathy:pathophysiology:Cellular%20ATP%20Depletion","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Cellular ATP Depletion","description":"Energy deprivation was measured in m.8993T>C patient lymphocytes. Related m.9035T>C cybrids had less than half the control steady-state ATP content. 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Nuclear, haplogroup and copy-number modifiers remain candidate explanations rather than demonstrated determinants here.","url":"https://dismech.monarchinitiative.org/pages/disorders/Adult-Onset_Ataxia_and_Polyneuropathy.html#pathophysiology-heteroplasmy-dependent-expression","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAdult-Onset_Ataxia_and_Polyneuropathy:pathophysiology:MT-ATP6%20m.8993T%3EC%20Variant","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"MT-ATP6 m.8993T>C Variant","description":"The defining mitochondrial m.8993T>C missense variant substitutes proline for leucine at ATP6 residue 156. ATP6 encodes subunit a of ATP synthase. 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These experiments do not establish that ROS determines adult onset or prove neuronal injury in vivo.","url":"https://dismech.monarchinitiative.org/pages/disorders/Adult-Onset_Ataxia_and_Polyneuropathy.html#pathophysiology-reactive-oxygen-species-overproduction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Adult-Onset_Ataxia_and_Polyneuropathy.yaml:Patient primary fibroblasts with homoplasmic m.9035T>C","source_id":"model:kb/disorders/Adult-Onset_Ataxia_and_Polyneuropathy.yaml:Patient primary fibroblasts with homoplasmic m.9035T>C","target_id":"node:disorder%3AAdult-Onset_Ataxia_and_Polyneuropathy:pathophysiology:Impaired%20ATP%20Synthase%20Function","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Partially Recapitulates","directed":false,"relationship":"PARTIALLY_RECAPITULATES","fidelity":"LOW","causal_link_type":null,"causal_link_type_label":null,"description":"Assay-specific evidence for mitochondrial dysfunction.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AAdult-Onset_Ataxia_and_Polyneuropathy:1:0","source_id":"node:disorder%3AAdult-Onset_Ataxia_and_Polyneuropathy:pathophysiology:Heteroplasmy-Dependent%20Expression","target_id":"node:disorder%3AAdult-Onset_Ataxia_and_Polyneuropathy:pathophysiology:Impaired%20ATP%20Synthase%20Function","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[0]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"Mutant load can modify the expression of mitochondrial dysfunction; 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Disease-associated variants are distributed across the actin-binding calponin-homology domains, the spectrin-repeat rod, and the C-terminal EF-hand/calmodulin-like region; they perturb actin binding, titin interaction, Z-disc incorporation, protein stability, or partner binding rather than abolishing the protein, and haploinsufficiency is not an established mechanism.","url":"https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy_1AA.html#pathophysiology-alpha-actinin-2-z-disc-dysfunction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ADilated_Cardiomyopathy_1AA:pathophysiology:Sarcomeric%20Disarray%20and%20Cardiomyocyte%20Hypertrophy","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Sarcomeric Disarray and Cardiomyocyte Hypertrophy","description":"The converging consequence of impaired Z-disc mechanics and (for some variants) mutant protein destabilization is disorganized myofibrillar architecture with hypertrophic growth of the cardiomyocyte. 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In ACTN2 disease the net geometry is variable — the same gene, and sometimes the same variant, can yield a dilated, hypertrophic, restrictive, or noncompacted ventricle, and the dominant pattern can differ between relatives — but the remodeling machinery itself is the conserved cardiomyopathy step.","url":"https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy_1AA.html#pathophysiology-adverse-ventricular-remodeling","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ADilated_Cardiomyopathy_1AA:pathophysiology:Impaired%20Z-Disc%20Force%20Transmission%20and%20Myofilament%20Regulation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Z-Disc Force Transmission and Myofilament Regulation","description":"Because the Z-disc both transmits force between sarcomeres and relays regulatory information to the thin and thick filaments, an abnormal alpha-actinin-2 degrades contraction and relaxation simultaneously. 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In isogenic hiPSC-cardiomyocyte models the mutant allele produces protein aggregation, multinucleation, hypertrophy, and myofibrillar disarray with activation of both the ubiquitin-proteasome system and the autophagy-lysosome pathway, loss of sarcomere-associated proteins, and reduced force in engineered heart tissue; an Actn2 missense knock-in mouse independently shows a destabilized protein with increased ubiquitin-proteasome activity. This proteopathy arm is variant-specific and has not been demonstrated in patient myocardium.","url":"https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy_1AA.html#pathophysiology-mutant-alpha-actinin-2-destabilization-and-proteostatic-stress","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ADilated_Cardiomyopathy_1AA:pathophysiology:Neurohormonal%20Activation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Neurohormonal Activation","description":"As in other cardiomyopathies, the fall in contractile performance activates the renin-angiotensin-aldosterone and sympathetic systems. 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Voluntary cough improved clearance and represents a partly compensating mechanism; regional deposition and cough complicate interpretation of whole-lung tracer measurements.","url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Ciliary_Dyskinesia.html#pathophysiology-impaired-mucociliary-clearance","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Primary_Ciliary_Dyskinesia.yaml:Patient-derived airway organoid model","source_id":"model:kb/disorders/Primary_Ciliary_Dyskinesia.yaml:Patient-derived airway organoid 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ciliary beating"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[{"statement":"Patient-derived airway organoids reproduce mutation-linked differences in ciliary beating and support genotype-specific functional interrogation","evidence":[{"reference":"PMID:34693619","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/34693619","reference_title":"Modelling of primary ciliary dyskinesia using patient-derived airway organoids.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Patient-specific differences in ciliary beating are observed and are in agreement with the patients' genetic mutations.","explanation":"Supports the organoid model as a genotype-resolved readout of the ciliary dysfunction central to PCD."},{"reference":"PMID:34693619","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/34693619","reference_title":"Modelling of primary ciliary dyskinesia using patient-derived airway organoids.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"More detailed organoid ciliary phenotypes can thus be documented in addition to the standard diagnostic procedure.","explanation":"Supports use of organoids for mechanistically richer ciliary phenotyping in PCD."}]}],"findings_text":["Patient-derived airway organoids reproduce mutation-linked differences in ciliary beating and support genotype-specific functional interrogation"],"evidence":[{"reference":"PMID:34693619","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/34693619","reference_title":"Modelling of primary ciliary dyskinesia using patient-derived airway organoids.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We apply this condition to AOs established from nasal inferior turbinate brush samples of patients suffering from primary ciliary dyskinesia (PCD), a pulmonary disease caused by dysfunction of the motile cilia in the airways.","explanation":"Establishes 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mechanistically richer ciliary phenotyping in PCD."}],"evidence_text":["We apply this condition to AOs established from nasal inferior turbinate brush samples of patients suffering from primary ciliary dyskinesia (PCD), a pulmonary disease caused by dysfunction of the motile cilia in the airways.","Patient-specific differences in ciliary beating are observed and are in agreement with the patients' genetic mutations.","More detailed organoid ciliary phenotypes can thus be documented in addition to the standard diagnostic procedure.","Establishes patient-derived airway organoids as a directly disease-relevant non-animal model for PCD.","Supports the organoid model as a genotype-resolved readout of the ciliary dysfunction central to PCD.","Supports use of organoids for mechanistically richer ciliary phenotyping in PCD."],"evidence_status":"Evidence recorded","metadata_completeness":100,"metadata_present":["Model category","NAMO class","Organism","Anatomy","Cell type","Cell 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Defective CFTR impairs epithelial anion and water handling, creating dehydrated secretions that initiate respiratory, gastrointestinal, hepatobiliary, sweat-gland, and reproductive disease.","url":"https://dismech.monarchinitiative.org/pages/disorders/Cystic_Fibrosis.html#pathophysiology-cftr-dysfunction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACystic_Fibrosis:pathophysiology:Airway%20Surface%20Liquid%20Acidification","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Airway Surface Liquid Acidification","description":"Loss of CFTR-mediated bicarbonate secretion lowers the pH of the thin airway surface liquid layer. Acidic airway surface liquid inhibits the antimicrobial activity of the secreted host-defence proteins it carries, so bacteria landing on the surface are killed less efficiently. This arm is separable from volume depletion and from mucus stasis: in newborn cystic fibrosis pigs it is present at birth, before any infection or inflammation. The amount of CFTR is rate-limiting for bicarbonate secretion over its whole range, unlike chloride secretion, which plateaus once a minority of cells express CFTR; that dose relationship has been established in mixed porcine airway epithelia and in cultured human bronchial epithelium rather than across human tissues, genotypes and disease stages, so it should not be read as a universal bicarbonate-over-chloride hierarchy.","url":"https://dismech.monarchinitiative.org/pages/disorders/Cystic_Fibrosis.html#pathophysiology-airway-surface-liquid-acidification","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACystic_Fibrosis:pathophysiology:Airway%20Surface%20Liquid%20Depletion","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Airway Surface Liquid Depletion","description":"Reduced epithelial anion secretion together with increased sodium absorption depletes the periciliary liquid layer and airway surface liquid.","url":"https://dismech.monarchinitiative.org/pages/disorders/Cystic_Fibrosis.html#pathophysiology-airway-surface-liquid-depletion","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACystic_Fibrosis:pathophysiology:ENaC%20Hyperactivity%20and%20Sodium%20Hyperabsorption","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"ENaC Hyperactivity and Sodium Hyperabsorption","description":"In CF airways, reduced CFTR function disinhibits ENaC, increasing epithelial sodium and water absorption and worsening airway dehydration.","url":"https://dismech.monarchinitiative.org/pages/disorders/Cystic_Fibrosis.html#pathophysiology-enac-hyperactivity-and-sodium-hyperabsorption","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACystic_Fibrosis:pathophysiology:Hepatobiliary%20Obstruction","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Hepatobiliary Obstruction","description":"CFTR dysfunction in cholangiocytes causes viscid bile secretions that obstruct intrahepatic bile ductules. This leads to focal biliary cirrhosis, which can progress to multilobular cirrhosis with portal hypertension in 5-10% of CF patients. CF liver disease is the third leading cause of death after respiratory failure and transplant complications.","url":"https://dismech.monarchinitiative.org/pages/disorders/Cystic_Fibrosis.html#pathophysiology-hepatobiliary-obstruction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACystic_Fibrosis:pathophysiology:Impaired%20Pancreatic%20Organogenesis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Pancreatic Organogenesis","description":"CFTR dysfunction during fetal pancreatic development impairs the organogenesis of both endocrine and exocrine pancreatic tissue. Clinical evidence demonstrates that CF patients present with pancreatic pathology and glucose abnormalities as early as in utero. CFTR's role during pancreatic development may reduce pancreatic mass and islet cell number from birth, establishing a developmental foundation that predisposes to CF-related diabetes (CFRD) and exocrine insufficiency, distinct from post-natal destruction mechanisms.","url":"https://dismech.monarchinitiative.org/pages/disorders/Cystic_Fibrosis.html#pathophysiology-impaired-pancreatic-organogenesis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACystic_Fibrosis:pathophysiology:Intestinal%20Obstruction","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Intestinal Obstruction","description":"Dehydrated intestinal secretions cause bowel obstruction at different ages. Meconium ileus occurs in 15-20% of CF neonates due to inspissated meconium in the distal ileum. In older children and adults, distal intestinal obstruction syndrome (DIOS) presents with similar pathophysiology in the ileocecal region. Constipation is also common due to dehydrated intestinal contents.","url":"https://dismech.monarchinitiative.org/pages/disorders/Cystic_Fibrosis.html#pathophysiology-intestinal-obstruction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACystic_Fibrosis:pathophysiology:Macrophage%20CFTR%20Dysfunction","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Macrophage CFTR Dysfunction","description":"CFTR is expressed and functional in monocyte-derived macrophages, and macrophages from people with cystic fibrosis show reduced phagocytosis, reduced intracellular killing of cystic fibrosis pathogens, and reduced efferocytosis of apoptotic neutrophils. Elexacaftor/tezacaftor/ivacaftor partially restores these effector functions while leaving inflammatory cytokine production unchanged, which places the defect at least partly within the immune cell rather than entirely downstream of the epithelial surface. The evidence is ex vivo, from blood-derived macrophages, so the independent contribution of this arm to airway disease in vivo is not quantified and it should not be generalized to every immune lineage.","url":"https://dismech.monarchinitiative.org/pages/disorders/Cystic_Fibrosis.html#pathophysiology-macrophage-cftr-dysfunction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACystic_Fibrosis:pathophysiology:Pancreatic%20Duct%20Obstruction","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Pancreatic Duct Obstruction","description":"CFTR dysfunction in pancreatic ductal epithelium impairs bicarbonate and fluid secretion, leading to viscid secretions that obstruct pancreatic ducts.","url":"https://dismech.monarchinitiative.org/pages/disorders/Cystic_Fibrosis.html#pathophysiology-pancreatic-duct-obstruction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACystic_Fibrosis:phenotype:Reduced%20Female%20Fertility","kind":"phenotype","kind_label":"Phenotype","label":"Reduced Female Fertility","description":"Reduced fertility in females with CF due to thick cervical mucus that impairs sperm transport. Fertility is improved with CFTR modulator therapy and nutritional optimization.","url":"https://dismech.monarchinitiative.org/pages/disorders/Cystic_Fibrosis.html#phenotype-reduced-female-fertility","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACystic_Fibrosis:pathophysiology:Sinonasal%20Disease","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Sinonasal Disease","description":"CFTR dysfunction in the sinonasal epithelium causes mucus retention and chronic inflammation in the paranasal sinuses. Chronic rhinosinusitis affects nearly all CF patients. Nasal polyposis occurs in 10-32% of CF patients and is unusual in children without CF, making it an important diagnostic clue.","url":"https://dismech.monarchinitiative.org/pages/disorders/Cystic_Fibrosis.html#pathophysiology-sinonasal-disease","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACystic_Fibrosis:pathophysiology:Sweat%20Gland%20Dysfunction","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Sweat Gland Dysfunction","description":"In sweat glands, CFTR is required for chloride reabsorption in the sweat duct. Loss of CFTR function results in failure to reabsorb chloride from primary sweat, producing sweat with elevated chloride concentration. This is the basis of the diagnostic sweat chloride test. Excessive salt loss can cause hyponatremic dehydration, especially in hot weather or during exercise.","url":"https://dismech.monarchinitiative.org/pages/disorders/Cystic_Fibrosis.html#pathophysiology-sweat-gland-dysfunction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACystic_Fibrosis:pathophysiology:Vas%20Deferens%20Agenesis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Vas Deferens Agenesis","description":"CFTR is required for normal development of the Wolffian duct derivatives. Congenital bilateral absence of the vas deferens (CBAVD) occurs in approximately 97-98% of males with CF due to inspissation and atresia of the vas deferens during fetal development. CBAVD causes obstructive azoospermia and male infertility. 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RNA-seq gene-set enrichment implicated EMT and TNF-alpha/NF-kappaB signatures, but no pathway-inhibition experiment established their causal role.","notes":null,"context_id":"disorder:BEST1_Bestrophinopathies","context_kind":"Disorder","disease_name":"BEST1 Bestrophinopathies","disease_synonyms":[],"disease_term":{"id":null,"label":"BEST1 bestrophinopathy spectrum","display_label":"BEST1 bestrophinopathy spectrum","url":null},"experimental_model_type":"IPSC_DERIVED_MODEL","experimental_model_type_label":"iPSC-derived model","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[{"id":"CL:0002586","label":"retinal pigment epithelial cell","display_label":"Retinal pigment epithelial cell","url":"http://purl.obolibrary.org/obo/CL_0002586"}],"linked_cell_type_labels":["retinal pigment epithelial cell"],"cell_types":[{"id":"CL:0002586","label":"retinal pigment epithelial cell","display_label":"Retinal pigment epithelial cell","url":"http://purl.obolibrary.org/obo/CL_0002586"}],"cell_type_labels":["retinal pigment epithelial cell"],"conditions":[],"cell_source":"Peripheral blood mononuclear cells from one ARB patient, one dominant Best disease patient and two unaffected controls.","source_category":"Patient-derived","culture_system":null,"publication":"PMID:32882766","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32882766","mechanisms":[{"target":"Reduced RPE Transepithelial Fluid Transport","target_url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathophysiology-reduced-rpe-transepithelial-fluid-transport","relationship":"PARTIALLY_RECAPITULATES","relationship_label":"Partially Recapitulates","fidelity":"NOT_SPECIFIED","fidelity_label":"Not Specified","description":null,"limitations":"One donor per disease group, no isogenic correction and no intact photoreceptor-RPE interface; gene-set enrichment does not demonstrate epithelial transition or pathway causation in patients.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[{"id":"CL:0002586","label":"retinal pigment epithelial cell","display_label":"Retinal pigment epithelial cell","url":"http://purl.obolibrary.org/obo/CL_0002586"}],"biological_processes":[],"pathways":[],"genes":[],"chemicals":[],"readouts":[],"evidence":[],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:BEST1_Bestrophinopathies","model_node_id":"model:kb/disorders/BEST1_Bestrophinopathies.yaml:Patient-derived ARB and dominant Best disease iPSC-RPE fluid-transport model","focus_node_id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:Reduced%20RPE%20Transepithelial%20Fluid%20Transport","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathograph","nodes":[{"id":"model:kb/disorders/BEST1_Bestrophinopathies.yaml:Patient-derived ARB and dominant Best disease iPSC-RPE fluid-transport model","kind":"experimental_model","kind_label":"NAM model","label":"Patient-derived ARB and dominant Best disease iPSC-RPE fluid-transport model","description":"Differentiated RPE monolayers on permeable supports were tested for apical-to-basal fluid flow and electrical resistance. 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This cellular transport defect provides a candidate explanation for fluid accumulation; the small donor sample does not establish its magnitude across BEST1 genotypes or demonstrate that epithelial barrier breakdown is required.","url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathophysiology-reduced-rpe-transepithelial-fluid-transport","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:BEST1%20Channel%20Dysfunction","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"BEST1 Channel Dysfunction","description":"BEST1 encodes a pentameric calcium-activated anion channel of the RPE basolateral membrane. Variant effects differ: selected dominant patient-derived RPE lines have greatly reduced calcium-activated chloride currents, whereas p.Pro77Ser RPE shows increased halide permeability in a fluorescent biosensor assay. Reduced protein abundance, altered localization and channel-gating defects are allele-dependent. Dominant inheritance does not imply a uniform dominant-negative loss of channel activity.","url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1_Bestrophinopathies.html#pathophysiology-best1-channel-dysfunction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ABEST1_Bestrophinopathies:pathophysiology:Subretinal%20Fluid%20Accumulation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Subretinal Fluid Accumulation","description":"Subretinal fluid is observed in BEST1-associated retinopathy, often persistent in ARB. Impaired RPE fluid handling is a candidate contributor, while neovascular leakage requires separate assessment. 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In late stages, choroidal neovascularization (CNV) can develop beneath the damaged RPE, causing exudative complications and acute vision loss on a background of slow chronic progression.","url":"https://dismech.monarchinitiative.org/pages/disorders/BEST1-Related_Dominant_Retinopathy.html#pathophysiology-progressive-photoreceptor-damage-and-vision-loss","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ABEST1-Related_Dominant_Retinopathy:pathophysiology:RPE%20Dysfunction%20and%20Impaired%20Phagocytosis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"RPE Dysfunction and Impaired Phagocytosis","description":"Bestrophin-1 CaCC dysfunction impairs multiple interdependent RPE functions: calcium homeostasis, transepithelial fluid transport, and phagocytic uptake of daily-shed photoreceptor outer segments (POS). 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This is the model that works where the heterozygous mouse does not, and it is also the model that disagrees with the mouse about what the nuclear lesion looks like. Isogenic controls - genomically corrected patient lines and engineered deletion in healthy lines - are available and were used in the RANBP17 work, which is what makes the transport findings attributable to the allele rather than to line background.","url":"https://dismech.monarchinitiative.org/pages/disorders/Early-onset_Generalized_Limb-onset_Dystonia.html#experimental-model-patient-derived-cholinergic-motor-neurons","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEarly-onset_Generalized_Limb-onset_Dystonia:pathophysiology:Neuronal%20Nuclear%20Envelope%20Disruption","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Neuronal Nuclear Envelope Disruption","description":"Loss of torsinA function produces abnormal nuclear envelope architecture that is, strikingly, restricted to neurons even though TOR1A is widely expressed - the classic statement of the tissue-specificity problem in this disease. 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See the HUMAN_MODEL_MISMATCH discussion.","url":"https://dismech.monarchinitiative.org/pages/disorders/Early-onset_Generalized_Limb-onset_Dystonia.html#pathophysiology-neuronal-nuclear-envelope-disruption","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEarly-onset_Generalized_Limb-onset_Dystonia:pathophysiology:Impaired%20Nucleocytoplasmic%20Transport","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Nucleocytoplasmic Transport","description":"Patient-derived DYT1 motor neurons show impaired bidirectional traffic across the nuclear envelope, affecting both protein import and export and the export of mRNA. 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That rescue is what makes this node causal rather than merely correlated, and it places impaired transport upstream of the developmental abnormality rather than beside it.","url":"https://dismech.monarchinitiative.org/pages/disorders/Early-onset_Generalized_Limb-onset_Dystonia.html#pathophysiology-impaired-nucleocytoplasmic-transport","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEarly-onset_Generalized_Limb-onset_Dystonia:pathophysiology:Impaired%20TorsinA%20AAA%2B%20ATPase%20Function","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired TorsinA AAA+ ATPase Function","description":"TorsinA is an AAA+ ATPase resident in the endoplasmic reticulum lumen and the contiguous perinuclear space. 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The functional readout that matters is not the catalytic rate in isolation but the ability to rescue nuclear envelope defects in torsin-deficient cells.","url":"https://dismech.monarchinitiative.org/pages/disorders/Early-onset_Generalized_Limb-onset_Dystonia.html#pathophysiology-impaired-torsina-aaa-atpase-function","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEarly-onset_Generalized_Limb-onset_Dystonia:pathophysiology:Maturation-Dependent%20Disruption%20of%20Neuronal%20Development","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Maturation-Dependent Disruption of Neuronal Development","description":"The consequences of torsinA loss are tied to a developmental window rather than to progressive adult injury. 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This node is why the disease is described as functional and developmental rather than degenerative, and it is the mechanistic counterpart of the clinical observation that symptoms begin in childhood, spread over a few years, and then persist without shortening life span.","url":"https://dismech.monarchinitiative.org/pages/disorders/Early-onset_Generalized_Limb-onset_Dystonia.html#pathophysiology-maturation-dependent-disruption-of-neuronal-development","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:1:model:kb/disorders/Early-onset_Generalized_Limb-onset_Dystonia.yaml:Patient-derived cholinergic motor neurons","source_id":"model:kb/disorders/Early-onset_Generalized_Limb-onset_Dystonia.yaml:Patient-derived cholinergic motor neurons","target_id":"node:disorder%3AEarly-onset_Generalized_Limb-onset_Dystonia:pathophysiology:Neuronal%20Nuclear%20Envelope%20Disruption","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[1]","label":"Partially Recapitulates","directed":false,"relationship":"PARTIALLY_RECAPITULATES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"Reproduces nuclear envelope pathology - markedly thickened nuclear lamina, disrupted nuclear morphology, LMNB1 upregulation and mislocalization - but not the perinuclear blebs that are the signature lesion in the mouse models. 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heterozygous TOR1A mutation","explanation":"Establishes that the model carries the human disease genotype at the human zygosity, which is what makes it informative where the mouse is not."},{"reference":"PMID:33468570","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33468570","reference_title":"Disease Modeling with Human Neurons Reveals LMNB1 Dysregulation Underlying DYT1 Dystonia.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"impaired nucleocytoplasmic transport (NCT) of mRNAs and proteins","explanation":"Reports the transport measurement in patient-derived neurons."},{"reference":"PMID:38438257","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38438257","reference_title":"RANBP17 Overexpression Restores Nucleocytoplasmic Transport and Ameliorates Neurodevelopment in Induced DYT1 Dystonia Motor Neurons.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"the overexpression of RANBP17 emerged as a substantial mitigating factor, effectively restoring 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models","explanation":"Records the negative finding in full: the human patient-derived motor neurons lack the lesion that defines the mouse models."}],"evidence_text":["These patient-specific neurons retain the donor's heterozygous TOR1A mutation","impaired nucleocytoplasmic transport (NCT) of mRNAs and proteins","the overexpression of RANBP17 emerged as a substantial mitigating factor, effectively restoring impaired NCT activity and rescuing neurodevelopmental deficits observed in DYT1 MNs","markedly thickened nuclear lamina, disrupted nuclear morphology","whereas they lack the perinuclear \"blebs\" that are often observed in animal models","Establishes that the model carries the human disease genotype at the human zygosity, which is what makes it informative where the mouse is not.","Reports the transport measurement in patient-derived neurons.","Reports restoration of both the transport readout and the developmental phenotype.","Reports the envelope pathology that is present, which 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This is the flagship human model of the disorder and the reason the microcephaly can be attributed to a progenitor-proliferation defect rather than to postnatal degeneration alone.","notes":null,"context_id":"disorder:Neurodevelopmental_Disorder_with_Microcephaly_Impaired_Language_and_Gait_Abnormalities","context_kind":"Disorder","disease_name":"Neurodevelopmental Disorder with Microcephaly, Impaired Language, and Gait Abnormalities","disease_synonyms":["NEDMILG","NEDMILG, AR","neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, autosomal recessive","NARS1-related neurodevelopmental disorder, autosomal recessive","asparaginyl-tRNA synthetase 1 deficiency"],"disease_term":{"id":"MONDO:0100348","label":"neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities","display_label":"neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities","url":"http://purl.obolibrary.org/obo/MONDO_0100348"},"experimental_model_type":"ORGANOID","experimental_model_type_label":"Organoid","namo_type":"namo:Organoid","declared_namo_class_name":null,"namo_class_name":"Organoid","namo_class_label":"Organoid","namo_description":"A 3D cell culture system that self-organizes to recapitulate key structural and functional aspects of an organ or tissue","namo_docs_url":"https://monarch-initiative.github.io/namo/elements/Organoid/","namo_ontology_url":"https://w3id.org/monarch-initiative/namo/Organoid","namo_mapping_basis":"Safe mapping from DisMech category","namo_class_in_schema":true,"namo_schema_status":"Defined in NAMO schema used for this build","modality":"Cellular system","organism":{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},"organism_label":"Homo sapiens","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[{"id":"CL:0000681","label":"radial glial cell","display_label":"radial glial cell","url":"http://purl.obolibrary.org/obo/CL_0000681"}],"model_cell_type_labels":["radial glial cell"],"linked_cell_types":[{"id":"CL:0000681","label":"radial glial cell","display_label":"radial glial cell","url":"http://purl.obolibrary.org/obo/CL_0000681"},{"id":"CL:0000127","label":"astrocyte","display_label":"astrocyte","url":"http://purl.obolibrary.org/obo/CL_0000127"}],"linked_cell_type_labels":["radial glial cell","astrocyte"],"cell_types":[{"id":"CL:0000681","label":"radial glial cell","display_label":"radial glial cell","url":"http://purl.obolibrary.org/obo/CL_0000681"},{"id":"CL:0000127","label":"astrocyte","display_label":"astrocyte","url":"http://purl.obolibrary.org/obo/CL_0000127"}],"cell_type_labels":["radial glial cell","astrocyte"],"conditions":[],"cell_source":"iPSC reprogrammed from patient fibroblasts (families MIC-1433 and MIC-2116)","source_category":"Patient-derived","culture_system":null,"publication":"PMID:32788587","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32788587","mechanisms":[{"target":"Radial Glial Progenitor Proliferation Failure","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Neurodevelopmental_Disorder_with_Microcephaly,_Impaired_Language,_and_Gait_Abnormalities.html#pathophysiology-radial-glial-progenitor-proliferation-failure","relationship":"RECAPITULATES","relationship_label":"Recapitulates","fidelity":"HIGH","fidelity_label":"High","description":"The organoid reproduces the human progenitor defect directly: reduced radial glial proliferation, fewer and smaller SOX2-positive neural rosettes, and depletion of TUJ1-positive post-mitotic neurons.","limitations":"Cortical organoids model fetal corticogenesis only. 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How pool depletion produces neuronal injury specifically is not established — see the gap_pyrimidine_depletion_to_neuronal_injury discussion.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1}]}}],"mechanism_names":["Pyrimidine Nucleotide and UDP-Sugar Pool Depletion"],"relationships":["Measures"],"fidelities":["High"],"biological_scales":["Cellular"],"system_context_sources":["Model-level cell type","Linked mechanism cell type","Linked mechanism biological scale"],"modeled_system_labels":["skin fibroblast","neuron","erythroid lineage cell","Cellular"],"biological_process_terms":[{"id":"GO:0044205","label":"'de novo' UMP biosynthetic process","display_label":"'de novo' UMP biosynthetic process","url":"http://purl.obolibrary.org/obo/GO_0044205"}],"biological_processes":["'de novo' UMP biosynthetic process"],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":["CTP, UTP and UDP-activated sugar levels"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:32820246","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/32820246","reference_title":"Expanding the clinical and genetic spectrum of CAD deficiency: an epileptic encephalopathy treatable with uridine supplementation.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"the diagnosis relies on genetic testing and functional validation in patient-derived fibroblasts","explanation":"Establishes that this system is not merely a research model but part of the diagnostic pathway."},{"reference":"PMID:25678555","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/25678555","reference_title":"Biallelic mutations in CAD, impair de novo pyrimidine biosynthesis and decrease glycosylation precursors.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Metabolic flux studies showed impaired aspartate incorporation into RNA and DNA through the de novo synthesis pathway.","explanation":"Establishes the system as carrying the disease biochemistry."},{"reference":"PMID:25678555","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/25678555","reference_title":"Biallelic mutations in CAD, impair de novo pyrimidine biosynthesis and decrease glycosylation precursors.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"CTP, UTP and nearly all UDP-activated sugars that serve as donors for glycosylation were decreased.","explanation":"The measurement and its direction."}],"evidence_text":["the diagnosis relies on genetic testing and functional validation in patient-derived fibroblasts","Metabolic flux studies showed impaired aspartate incorporation into RNA and DNA through the de novo synthesis pathway.","CTP, UTP and nearly all UDP-activated sugars that serve as donors for glycosylation were decreased.","Establishes that this system is not merely a research model but part of the diagnostic pathway.","Establishes the system as carrying the disease biochemistry.","The measurement and its direction."],"evidence_status":"Evidence recorded","metadata_completeness":60,"metadata_present":["Model category","Organism","Cell type","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Anatomy","Cell source","Culture system"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Developmental_And_Epileptic_Encephalopathy_50.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Developmental_And_Epileptic_Encephalopathy_50.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Developmental_and_Epileptic_Encephalopathy_50.html#experimental-model-patient-derived-dermal-fibroblasts","source_anchor":"experimental-model-patient-derived-dermal-fibroblasts"},{"id":"model:kb/disorders/Neurodevelopmental_Disorder_With_Dysmorphic_Facies_Sleep_Disturbance_And_Brain_Abnormalities.yaml:Patient-derived dermal fibroblasts","name":"Patient-derived dermal fibroblasts","description":"Primary dermal fibroblasts from two of the three affected individuals were used for bulk RNA sequencing against six controls, with RT-qPCR validation. 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No iPSC-derived neurons, brain organoids, or patient neural tissue have been studied.","notes":null,"context_id":"disorder:Neurodevelopmental_Disorder_With_Dysmorphic_Facies_Sleep_Disturbance_And_Brain_Abnormalities","context_kind":"Disorder","disease_name":"Neurodevelopmental Disorder With Dysmorphic Facies, Sleep Disturbance, and Brain Abnormalities","disease_synonyms":["NEDFASB","KAT5-related neurodevelopmental disorder","KAT5-related chromatinopathy","TIP60-related neurodevelopmental syndrome"],"disease_term":{"id":"MONDO:0030852","label":"neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalities","display_label":"neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalities","url":"http://purl.obolibrary.org/obo/MONDO_0030852"},"experimental_model_type":"PRIMARY_CELL_CULTURE","experimental_model_type_label":"Primary-cell culture","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},"organism_label":"Homo sapiens","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[{"id":"UBERON:0001898","label":"hypothalamus","display_label":"hypothalamus","url":"http://purl.obolibrary.org/obo/UBERON_0001898"}],"linked_anatomy_labels":["hypothalamus"],"anatomy":[{"id":"UBERON:0001898","label":"hypothalamus","display_label":"hypothalamus","url":"http://purl.obolibrary.org/obo/UBERON_0001898"}],"anatomy_labels":["hypothalamus"],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":null,"source_category":"Primary / biopsy-derived","culture_system":null,"publication":"PMID:32822602","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32822602","mechanisms":[{"target":"Chromatin-Dependent Dysregulation of Developmental Transcription","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Neurodevelopmental_Disorder_With_Dysmorphic_Facies,_Sleep_Disturbance,_and_Brain_Abnormalities.html#pathophysiology-chromatin-dependent-dysregulation-of-developmental-transcription","relationship":"MEASURES","relationship_label":"Measures","fidelity":"MODERATE","fidelity_label":"Moderate","description":"Bulk RNA sequencing of patient versus control fibroblasts is the assay that established deregulation of developmental genes downstream of the histone acetylation deficit.","limitations":"Dermal fibroblasts are a peripheral surrogate; the affected tissues are brain, cerebellum and cranial neural crest derivatives, so the transcriptional signature may not be the one operating in disease-relevant cells.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0006325","label":"chromatin organization","display_label":"chromatin organization","url":"http://purl.obolibrary.org/obo/GO_0006325"},{"id":"GO:0006357","label":"regulation of transcription by RNA polymerase II","display_label":"regulation of transcription by RNA polymerase II","url":"http://purl.obolibrary.org/obo/GO_0006357"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[],"evidence":[],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Neurodevelopmental_Disorder_With_Dysmorphic_Facies_Sleep_Disturbance_And_Brain_Abnormalities","model_node_id":"model:kb/disorders/Neurodevelopmental_Disorder_With_Dysmorphic_Facies_Sleep_Disturbance_And_Brain_Abnormalities.yaml:Patient-derived dermal fibroblasts","focus_node_id":"node:disorder%3ANeurodevelopmental_Disorder_With_Dysmorphic_Facies_Sleep_Disturbance_And_Brain_Abnormalities:pathophysiology:Chromatin-Dependent%20Dysregulation%20of%20Developmental%20Transcription","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Neurodevelopmental_Disorder_With_Dysmorphic_Facies,_Sleep_Disturbance,_and_Brain_Abnormalities.html#pathograph","nodes":[{"id":"model:kb/disorders/Neurodevelopmental_Disorder_With_Dysmorphic_Facies_Sleep_Disturbance_And_Brain_Abnormalities.yaml:Patient-derived dermal fibroblasts","kind":"experimental_model","kind_label":"NAM model","label":"Patient-derived dermal fibroblasts","description":"Primary dermal fibroblasts from two of the three affected individuals were used for bulk RNA sequencing against six controls, with RT-qPCR validation. 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No iPSC-derived neurons, brain organoids, or patient neural tissue have been studied.","url":"https://dismech.monarchinitiative.org/pages/disorders/Neurodevelopmental_Disorder_With_Dysmorphic_Facies,_Sleep_Disturbance,_and_Brain_Abnormalities.html#experimental-model-patient-derived-dermal-fibroblasts","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ANeurodevelopmental_Disorder_With_Dysmorphic_Facies_Sleep_Disturbance_And_Brain_Abnormalities:pathophysiology:Chromatin-Dependent%20Dysregulation%20of%20Developmental%20Transcription","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Chromatin-Dependent Dysregulation of Developmental Transcription","description":"Reduced histone H4 acetylation at NuA4/TIP60 target loci alters chromatin accessibility and RNA polymerase II-dependent transcription. 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PER1 and HDAC4 had previously been mapped as NuA4/TIP60-bound regions, supporting direct rather than incidental dysregulation.","url":"https://dismech.monarchinitiative.org/pages/disorders/Neurodevelopmental_Disorder_With_Dysmorphic_Facies,_Sleep_Disturbance,_and_Brain_Abnormalities.html#pathophysiology-chromatin-dependent-dysregulation-of-developmental-transcription","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ANeurodevelopmental_Disorder_With_Dysmorphic_Facies_Sleep_Disturbance_And_Brain_Abnormalities:pathophysiology:Impaired%20Cranial%20Neural%20Crest%20Expansion%20and%20Craniofacial%20Morphogenesis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Cranial Neural Crest Expansion and Craniofacial Morphogenesis","description":"The facial skeleton and palate derive from cranial neural crest cells. 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The authors of that work concluded that the orofacial clefting seen in individuals with heterozygous KAT5 missense variants is at least partly a cranial-neural-crest defect, which provides the mechanistic bridge from the chromatin lesion to the recognizable facial gestalt and the cleft/high-arched palate.","url":"https://dismech.monarchinitiative.org/pages/disorders/Neurodevelopmental_Disorder_With_Dysmorphic_Facies,_Sleep_Disturbance,_and_Brain_Abnormalities.html#pathophysiology-impaired-cranial-neural-crest-expansion-and-craniofacial-morphogenesis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ANeurodevelopmental_Disorder_With_Dysmorphic_Facies_Sleep_Disturbance_And_Brain_Abnormalities:pathophysiology:Impaired%20Neural%20Stem%20Cell%20Maintenance%20and%20Neurogenesis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Neural Stem Cell Maintenance and Neurogenesis","description":"Loss of Tip60/KAT5-dependent acetylation in neural stem and progenitor cells reduces progenitor proliferation, impairs neuronal differentiation and neuronal migration, and shifts the developmental programme prematurely from neurogenesis toward gliogenesis. Conditional Tip60 deletion in mouse NSCs reproduces microcephaly, a feature present in two of the three reported individuals.","url":"https://dismech.monarchinitiative.org/pages/disorders/Neurodevelopmental_Disorder_With_Dysmorphic_Facies,_Sleep_Disturbance,_and_Brain_Abnormalities.html#pathophysiology-impaired-neural-stem-cell-maintenance-and-neurogenesis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3ANeurodevelopmental_Disorder_With_Dysmorphic_Facies_Sleep_Disturbance_And_Brain_Abnormalities:pathophysiology:Impaired%20NuA4%2FTIP60%20Histone%20H4%20Acetyltransferase%20Activity","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired NuA4/TIP60 Histone H4 Acetyltransferase Activity","description":"Purified NuA4/TIP60 complexes containing the patient variants show decreased or abolished ability to acetylate the histone H4 tail in a chromatin context. p.Cys369Ser abolishes activity on both free histones and chromatin; p.Arg53His and p.Ser413Ala are predominantly defective on nucleosomal substrate, consistent with a chromatin-targeting rather than purely catalytic defect. Because complex assembly is preserved, the catalytically dead subunit is expected to occupy complexes that would otherwise contain wild-type KAT5, giving a dominant-interfering effect rather than simple haploinsufficiency.","url":"https://dismech.monarchinitiative.org/pages/disorders/Neurodevelopmental_Disorder_With_Dysmorphic_Facies,_Sleep_Disturbance,_and_Brain_Abnormalities.html#pathophysiology-impaired-nua4-tip60-histone-h4-acetyltransferase-activity","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"}],"edges":[{"id":"model-link:0:model:kb/disorders/Neurodevelopmental_Disorder_With_Dysmorphic_Facies_Sleep_Disturbance_And_Brain_Abnormalities.yaml:Patient-derived dermal 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this does not establish an isolated WNT readout."}],"evidence_text":["Organoids were generated from AS patients’ endometrium (n = 3) and from healthy control (n = 3) endometrium","Additionally, we obtained single-cell EEO results at P2, with a technical enrichment of organoid-forming cells, while the presence of XAV939 (a WNT inhibitor) in the EEO culture media may mask significant differences.","the transcriptomic profile of AS EEO cells became significantly different from WOI control EEO cells and in vivo counterparts, especially in the glandular secretory epithelium","Three AS organoid donors overlap the nine-person human atlas cohort.","Authors explicitly limit interpretation of the organoid comparison.","Actual organoid transcriptional comparison; this does not establish an isolated WNT readout."],"evidence_status":"Evidence recorded","metadata_completeness":60,"metadata_present":["Model category","NAMO class","Organism","Cell source","Publication","Evidence"],"metadata_missing":["Anatomy","Cell type","Culture system","Modeled mechanism"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Asherman_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Asherman_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Asherman_Syndrome.html#experimental-model-patient-derived-endometrial-epithelial-organoids","source_anchor":"experimental-model-patient-derived-endometrial-epithelial-organoids"},{"id":"model:kb/disorders/Hypertrophic_Cardiomyopathy_3.yaml:Patient-derived engineered heart tissue expressing TPM1 E192K","name":"Patient-derived engineered heart tissue expressing TPM1 E192K","description":"Three-dimensional engineered heart tissue generated from cardiomyocytes derived from patients carrying TPM1 E192K. 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Histology in TPM1-mutation hearts is indistinguishable from that of other sarcomeric causes, so the node is a faithful specialization of the generic ventricular-remodeling node rather than a TPM1-specific pathology. Human cardiac biopsies carrying TPM1 variants show loss of sarcomeric structure.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_3.html#pathophysiology-cardiomyocyte-hypertrophy-with-myofiber-disarray-and-interstitial-fibrosis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_3:pathophysiology:Diastolic%20Dysfunction%20and%20Left%20Ventricular%20Outflow%20Tract%20Obstruction","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Diastolic Dysfunction and Left Ventricular Outflow Tract Obstruction","description":"The stiffened, hypertrophied, fibrotic ventricle fills poorly, and when hypertrophy is asymmetric and septal it can also obstruct the left ventricular outflow tract dynamically. The clinical result is exertional dyspnoea, chest pain, and reduced exercise capacity with preserved or supranormal ejection fraction. 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features.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"the nuclear accumulation of p53 protein was confirmed in all analyzed ESCCOs and their parent tumor tissues, but not in ENOs or normal esophageal tissues","explanation":"Reports the measurement in tumor organoids, parental tissue, and the matched normal comparator."}],"evidence_text":["we established an ESCC organoid (ESCCO) library from 24 ESCC patients of various stages, ages, and treatments","the chemo-resistant ESCCOs show higher genes involved in antioxidant stress response pathways and more accessible chromatin at their loci than the sensitive ESCCOs","The ESCCOs respond differently to cisplatin and 5-fluorouracil, chemotherapeutic agents commonly used to treat ESCC patients, with 7 ESCCOs exhibiting potent chemo-resistance.","Through drug screening using the ESCCO library, we reveal that fedratinib effectively induces cell death in chemo-resistant ESCCOs.","These ESCCOs faithfully recapitulate the oncogenic mutations observed in the original ESCC tissues","the nuclear accumulation of p53 protein was confirmed in all analyzed ESCCOs and their parent tumor tissues, but not in ENOs or normal esophageal tissues","Establishes the scale and patient derivation of this human, animal-free ESCC model system.","Ties the model's measurements to the mechanism this node asserts, establishing it as informative for chemotherapy resistance in ESCC.","Reports the measured drug-response spread across the library and the number of resistant lines.","Reports increased cell death in the resistant lines on fedratinib exposure, measured in the organoid system.","Establishes that the organoids retain the parental tumor's oncogenic mutations, which is what makes them informative for a mutation-defined node.","Reports the measurement in tumor organoids, parental tissue, and the matched normal comparator."],"evidence_status":"Evidence recorded","metadata_completeness":100,"metadata_present":["Model category","NAMO class","Organism","Anatomy","Cell type","Cell source","Culture system","Modeled mechanism","Publication","Evidence"],"metadata_missing":[],"dataset_context":"Available in same entry","context_dataset_ids":["dataset:geo:gse289185"],"candidate_dataset_ids":[],"source_path":"kb/disorders/Esophageal_Squamous_Cell_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Esophageal_Squamous_Cell_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Esophageal_Squamous_Cell_Carcinoma.html#experimental-model-patient-derived-esophageal-squamous-cell-carcinoma-organoid-library-escco","source_anchor":"experimental-model-patient-derived-esophageal-squamous-cell-carcinoma-organoid-library-escco"},{"id":"model:kb/disorders/Ewing_Sarcoma.yaml:Patient-derived Ewing sarcoma culture panel","name":"Patient-derived Ewing sarcoma culture panel","description":"Patient-derived Ewing sarcoma cultures provide a primary-cell in vitro non-animal model for studying EWSR1 fusion status, proliferation, migration, and treatment response in models that differ transcriptionally from long-established cell lines.","notes":null,"context_id":"disorder:Ewing_Sarcoma","context_kind":"Disorder","disease_name":"Ewing Sarcoma","disease_synonyms":[],"disease_term":{"id":"MONDO:0012817","label":"Ewing sarcoma","display_label":"Ewing sarcoma","url":"http://purl.obolibrary.org/obo/MONDO_0012817"},"experimental_model_type":"PRIMARY_CELL_CULTURE","experimental_model_type_label":"Primary-cell culture","namo_type":"namo:TwoDCellCulture","declared_namo_class_name":"TwoDCellCulture","namo_class_name":"TwoDCellCulture","namo_class_label":"2D Cell Culture","namo_description":"Conventional monolayer cell cultures grown on flat surfaces. Simple but limited in physiological relevance.","namo_docs_url":"https://monarch-initiative.github.io/namo/elements/TwoDCellCulture/","namo_ontology_url":"https://w3id.org/monarch-initiative/namo/TwoDCellCulture","namo_mapping_basis":"Explicit in DisMech","namo_class_in_schema":true,"namo_schema_status":"Defined in NAMO schema used for this build","modality":"Cellular system","organism":{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},"organism_label":"Homo sapiens","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[{"id":"CL:0000134","label":"mesenchymal stem cell","display_label":"early mesenchymal stem cell","url":"http://purl.obolibrary.org/obo/CL_0000134"},{"id":"CL:0000333","label":"migratory neural crest cell","display_label":"migratory neural crest cell","url":"http://purl.obolibrary.org/obo/CL_0000333"}],"linked_cell_type_labels":["mesenchymal stem cell","migratory neural crest cell"],"cell_types":[{"id":"CL:0000134","label":"mesenchymal stem cell","display_label":"early mesenchymal stem cell","url":"http://purl.obolibrary.org/obo/CL_0000134"},{"id":"CL:0000333","label":"migratory neural crest cell","display_label":"migratory neural crest cell","url":"http://purl.obolibrary.org/obo/CL_0000333"}],"cell_type_labels":["mesenchymal stem cell","migratory neural crest cell"],"conditions":["Ewing sarcoma","patient-derived ES cultures","preclinical drug response testing"],"cell_source":"Patient-derived Ewing sarcoma tumor cultures","source_category":"Patient-derived","culture_system":"Patient-derived in vitro culture","publication":"PMID:41681984","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41681984","mechanisms":[{"target":"EWS-FLI1 Fusion Oncogene","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-ews-fli1-fusion-oncogene","relationship":"NOT_SPECIFIED","relationship_label":"Not Specified","fidelity":"NOT_SPECIFIED","fidelity_label":"Not Specified","description":"Models EWSR1 fusion-positive tumor state in patient-derived cultures.","limitations":null,"biological_scale":null,"anatomy":[],"cell_types":[{"id":"CL:0000134","label":"mesenchymal stem cell","display_label":"early mesenchymal stem cell","url":"http://purl.obolibrary.org/obo/CL_0000134"},{"id":"CL:0000333","label":"migratory neural crest cell","display_label":"migratory neural crest cell","url":"http://purl.obolibrary.org/obo/CL_0000333"}],"biological_processes":[{"id":"GO:0045944","label":"positive regulation of transcription by RNA polymerase II","display_label":"positive regulation of transcription by RNA polymerase II","url":"http://purl.obolibrary.org/obo/GO_0045944"}],"pathways":[],"genes":[{"id":"hgnc:3508","label":"EWSR1","display_label":"EWSR1","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/3508"},{"id":"hgnc:3749","label":"FLI1","display_label":"FLI1","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/3749"}],"chemicals":[],"readouts":[],"evidence":[],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Ewing_Sarcoma","model_node_id":"model:kb/disorders/Ewing_Sarcoma.yaml:Patient-derived Ewing sarcoma culture panel","focus_node_id":"node:disorder%3AEwing_Sarcoma:pathophysiology:EWS-FLI1%20Fusion%20Oncogene","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathograph","nodes":[{"id":"model:kb/disorders/Ewing_Sarcoma.yaml:Patient-derived Ewing sarcoma culture panel","kind":"experimental_model","kind_label":"NAM model","label":"Patient-derived Ewing sarcoma culture panel","description":"Patient-derived Ewing sarcoma cultures provide a primary-cell in vitro non-animal model for studying EWSR1 fusion status, proliferation, migration, and treatment response in models that differ transcriptionally from long-established cell lines.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#experimental-model-patient-derived-ewing-sarcoma-culture-panel","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:EWS-FLI1%20Fusion%20Oncogene","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"EWS-FLI1 Fusion Oncogene","description":"The t(11;22)(q24;q12) translocation fuses the EWS gene (EWSR1) on chromosome 22 with the FLI1 gene on chromosome 11. The resulting EWS-FLI1 protein functions as an aberrant FET-ETS transcription factor. It is the truncal driver of most Ewing sarcomas, but its oncogenic effect depends on a permissive developmental cell state and on downstream enhancer, transcriptional, metabolic, and DNA damage-response programs.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-ews-fli1-fusion-oncogene","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:ATF4-Serine-Glycine%20Metabolic%20Reprogramming","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"ATF4-Serine-Glycine Metabolic Reprogramming","description":"EWS-FLI1 and menin converge on ATF4 to activate a serine synthesis pathway transcriptional program. EWS-FLI1 also upregulates glutamine uptake and one-carbon cycle genes, linking fusion-driven transcription to biosynthetic metabolism, redox state, and survival.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-atf4-serine-glycine-metabolic-reprogramming","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:BAF%20Complex%20Retargeting","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"BAF Complex Retargeting","description":"EWS-FLI1 uses the EWSR1 low-complexity/prion-like domain to retarget BRG1/BRM-associated factor (BAF/SWI-SNF) chromatin-remodeling complexes to tumor-specific enhancers. This neomorphic recruitment depends on tyrosine residues linked to phase-transition behavior of the EWSR1 domain and helps establish oncogenic enhancer activity.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-baf-complex-retargeting","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:DHX9%20Sequestration%20During%20Topoisomerase%20Stress","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"DHX9 Sequestration During Topoisomerase Stress","description":"Following topoisomerase I poison exposure, EWS-FLI1 sequesters DHX9 helicase and prevents resolution of drug-induced R-loops. Excess DHX9 or reduced fusion expression confers SN-38 resistance independent of measured proliferation and global transcription rates. This supports a protein-interaction contribution under topoisomerase stress, without proving complete independence from transcription or untreated tumor initiation.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-dhx9-sequestration-during-topoisomerase-stress","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:EWS-FLI1%20Chromatin%20Hub%20Dynamics","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"EWS-FLI1 Chromatin Hub Dynamics","description":"EWS-FLI1 low-complexity-domain interactions support GGAA-associated transcription within a narrow interaction-strength optimum. A 2026 bioRxiv preprint reports endogenous dynamic sub-diffraction hubs that dissolve before macroscopic liquid-liquid phase separation. This is a provisional refinement of the published interaction-optimum model, not evidence that macroscopic condensates are required for oncogenesis.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-ews-fli1-chromatin-hub-dynamics","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:EWS-FLI1%20Dosage%20and%20State%20Plasticity","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"EWS-FLI1 Dosage and State Plasticity","description":"Fusion abundance and low-complexity-domain interaction strength are related but distinct control variables. TRIM8-mediated turnover prevents toxic fusion accumulation. Engineered graded depletion and restoration of endogenous EWS-FLI1 produce persistent transcriptional changes and increased metastatic behavior at intermediate depletion in preclinical models. This does not establish a clinical hazard of a particular inhibitor dose. Independently of those engineered perturbations, single-cell profiling of patient tumors associates an intermediate range of inferred fusion activity with proliferation and oxidative phosphorylation, and cells on either side of that range with a hypoxia program. That is a cross-sectional association in tumors, not a demonstration that fusion dose sets the program.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-ews-fli1-dosage-and-state-plasticity","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:EZH2-Associated%20Differentiation%20Repression","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"EZH2-Associated Differentiation Repression","description":"EWS-FLI1 induces EZH2, which contributes to repression of differentiation-associated genes and maintenance of an undifferentiated state. Genetic depletion impairs clonogenicity and tumorigenicity in preclinical systems. This dependency is distinct from the heterogeneous PRC2 changes following STAG2 loss and does not imply that every Ewing tumor will respond to an EZH2 inhibitor.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-ezh2-associated-differentiation-repression","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:GGAA%20Microsatellite%20Enhancer%20Reprogramming","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"GGAA Microsatellite Enhancer Reprogramming","description":"EWS-FLI1 binds GGAA microsatellite repeats and canonical ETS motifs, remodeling the enhancer landscape. At GGAA repeats, multimeric EWS-FLI1 opens chromatin and creates de novo enhancers that contact target promoters; at conserved ETS enhancers, EWS-FLI1 can displace wild-type ETS factors and repress tumor suppressor and lineage-regulatory programs.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-ggaa-microsatellite-enhancer-reprogramming","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:NuRD-LSD1%20Transcriptional%20Repression","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"NuRD-LSD1 Transcriptional Repression","description":"EWS-FLI1 recruits NuRD-associated HDAC and LSD1 activities to repress tumor-suppressive and lineage-regulatory genes. Repression contributes to transformation alongside enhancer activation. CHD4 also maintains global chromatin architecture and survival, but this distinct dependency should not be equated with regulation of EWS-FLI1 transcriptional output.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-nurd-lsd1-transcriptional-repression","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:PARP1-Supported%20Fusion%20Transcription","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"PARP1-Supported Fusion Transcription","description":"PARP1 interacts with EWS-FLI1 and EWS-ERG and supports fusion-mediated transcription; EWS-FLI1 also maintains PARP1 expression. This experimentally reported feedback connects transcription and damage response. The preclinical drug rationale has not translated into uniform clinical response.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-parp1-supported-fusion-transcription","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:Proposed%20POLQ%20Splicing%20and%20MMEJ%20Defect","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Proposed POLQ Splicing and MMEJ Defect","description":"A 2025 bioRxiv preprint reports that EWS-FLI1 expression or EWSR1 loss induces POLQ exon 25 skipping, reduces polymerase theta protein, and impairs microhomology-mediated end joining. Fusion knockdown and POLQ rescue support causality in tested models. Proposed synthetic lethality with other repair pathways requires independent replication and clinical evaluation; this is an emerging additional repair defect rather than a reason to erase the BRCA1 literature.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-proposed-polq-splicing-and-mmej-defect","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:SLFN11-Dependent%20Replication%20Fork%20Arrest","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"SLFN11-Dependent Replication Fork Arrest","description":"EWS-FLI1 directly increases SLFN11 expression. SLFN11 blocks stressed replication forks and promotes susceptibility to DNA-damaging agents. Expression-outcome correlations are not a validated standalone clinical selection test. Loss of SLFN11 can confer treatment resistance and is associated with metabolic adaptation in Ewing models.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-slfn11-dependent-replication-fork-arrest","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:Transcription-Coupled%20R-loop%20Accumulation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Transcription-Coupled R-loop Accumulation","description":"EWS-FLI1-driven transcription and impaired regulation of damage-induced transcription promote RNA:DNA hybrids and replication stress in Ewing cell models. The stress state creates DNA-damage vulnerabilities and dependence on buffering pathways. It does not itself cause enhanced survival, and it is not synonymous with a uniform BRCA-mutant clinical phenotype.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-transcription-coupled-r-loop-accumulation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:USP1-Survivin%20Stress%20Buffering","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"USP1-Survivin Stress Buffering","description":"EWS-FLI1 increases USP1 expression. USP1 stabilizes survivin and buffers replication-stress-associated apoptosis, allowing continued Ewing cell survival. USP1 inhibition sensitizes cells to doxorubicin and etoposide in preclinical experiments; human efficacy has not been established.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-usp1-survivin-stress-buffering","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"}],"edges":[{"id":"model-link:0:model:kb/disorders/Ewing_Sarcoma.yaml:Patient-derived Ewing sarcoma culture panel","source_id":"model:kb/disorders/Ewing_Sarcoma.yaml:Patient-derived Ewing sarcoma culture panel","target_id":"node:disorder%3AEwing_Sarcoma:pathophysiology:EWS-FLI1%20Fusion%20Oncogene","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Not 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CHD4 loss causes apoptosis and increases sensitivity to DNA-damaging agents; combined CHD4 depletion and olaparib suppressed xenograft growth.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-chd4-chromatin-architecture-maintenance","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:Core%20Regulatory%20Circuitry%20Activation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Core Regulatory Circuitry Activation","description":"EWS-FLI1 activates super-enhancers controlling a core regulatory circuitry composed of transcription factors including KLF15, TCF4, and NKX2-2. 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That is a cross-sectional association in tumors, not a demonstration that fusion dose sets the program.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-ews-fli1-dosage-and-state-plasticity","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:GGAA%20Microsatellite%20Germline%20Susceptibility%20Architecture","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"GGAA Microsatellite Germline Susceptibility Architecture","description":"Germline variation in GGAA microsatellite architecture can determine how strongly the acquired EWS-FLI1 fusion converts a locus into a neo-enhancer. 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YAP1/TAZ can oppose fusion transcription while promoting aggressive behavior in established tumors, so initiation and maintenance contexts require separate testing.","url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#pathophysiology-igf-1-yap1-developmental-cooperation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3AEwing_Sarcoma:pathophysiology:NuRD-LSD1%20Transcriptional%20Repression","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"NuRD-LSD1 Transcriptional Repression","description":"EWS-FLI1 recruits NuRD-associated HDAC and LSD1 activities to repress tumor-suppressive and lineage-regulatory genes. Repression contributes to transformation alongside enhancer activation. 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ES.","explanation":"Supports PDES as patient-derived, fusion-positive Ewing sarcoma models."}]}],"findings_text":["Patient-derived Ewing cultures retain EWSR1 fusion DNA."],"evidence":[{"reference":"PMID:41681984","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41681984","reference_title":"Characterisation of Bespoke Patient-Derived In Vitro Models of Ewing Sarcoma.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"To expedite this process, we have established and characterised patient-derived ES cultures (PDES) in vitro.","explanation":"Supports this as a patient-derived in vitro Ewing sarcoma model system."},{"reference":"PMID:41681984","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41681984","reference_title":"Characterisation of Bespoke Patient-Derived In Vitro Models of Ewing Sarcoma.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Results: All PDES contain EWSR1 fusion DNA, consistent with a diagnosis of ES.","explanation":"Supports PDES as patient-derived, fusion-positive Ewing sarcoma models."}],"evidence_text":["To expedite this process, we have established and characterised patient-derived ES cultures (PDES) in vitro.","Results: All PDES contain EWSR1 fusion DNA, consistent with a diagnosis of ES.","Supports this as a patient-derived in vitro Ewing sarcoma model system.","Supports PDES as patient-derived, fusion-positive Ewing sarcoma models."],"evidence_status":"Evidence recorded","metadata_completeness":90,"metadata_present":["Model category","NAMO class","Organism","Cell type","Cell source","Culture system","Modeled mechanism","Publication","Evidence"],"metadata_missing":["Anatomy"],"dataset_context":"Available in same 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Arg20His patient muscle retains about 40% of control assembled enzyme, whereas complete knockout cells lose detectable monomer, dimer and III2IV forms.","url":"https://dismech.monarchinitiative.org/pages/disorders/COX6B1-Related_COX_Deficiency.html#pathophysiology-reduced-mature-complex-iv-abundance","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/COX6B1-Related_COX_Deficiency.yaml:Patient-derived fibroblasts","source_id":"model:kb/disorders/COX6B1-Related_COX_Deficiency.yaml:Patient-derived fibroblasts","target_id":"node:disorder%3ACOX6B1-Related_COX_Deficiency:pathophysiology:Impaired%20stable%20COX6B1%20incorporation","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Partially Recapitulates","directed":false,"relationship":"PARTIALLY_RECAPITULATES","fidelity":"NOT_SPECIFIED","causal_link_type":null,"causal_link_type_label":null,"description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ACOX6B1-Related_COX_Deficiency:0:1","source_id":"node:disorder%3ACOX6B1-Related_COX_Deficiency:pathophysiology:Biallelic%20COX6B1%20dysfunction","target_id":"node:disorder%3ACOX6B1-Related_COX_Deficiency:pathophysiology:Impaired%20stable%20COX6B1%20incorporation","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[1]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"Arg20His alters stable incorporation despite retained total protein.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ACOX6B1-Related_COX_Deficiency:2:0","source_id":"node:disorder%3ACOX6B1-Related_COX_Deficiency:pathophysiology:Impaired%20stable%20COX6B1%20incorporation","target_id":"node:disorder%3ACOX6B1-Related_COX_Deficiency:pathophysiology:Reduced%20mature%20complex%20IV%20abundance","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[0]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"Poor stable incorporation accompanies reduced holoenzyme stability in patient samples.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":2}]}},{"target":"Reduced complex IV activity","target_url":"https://dismech.monarchinitiative.org/pages/disorders/COX6B1-Related_COX_Deficiency.html#pathophysiology-reduced-complex-iv-activity","relationship":"PARTIALLY_RECAPITULATES","relationship_label":"Partially Recapitulates","fidelity":"NOT_SPECIFIED","fidelity_label":"Not Specified","description":null,"limitations":"The system resolves cellular biochemical consequences and does not reproduce the full neurological and cardiac phenotype.","biological_scale":null,"anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0006123","label":"mitochondrial electron transport, cytochrome c to oxygen","display_label":"mitochondrial electron transport, cytochrome c to oxygen","url":"http://purl.obolibrary.org/obo/GO_0006123"}],"pathways":[],"genes":[{"id":"hgnc:2280","label":"COX6B1","display_label":"COX6B1","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/2280"}],"chemicals":[],"readouts":[],"evidence":[],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:COX6B1-Related_COX_Deficiency","model_node_id":"model:kb/disorders/COX6B1-Related_COX_Deficiency.yaml:Patient-derived fibroblasts","focus_node_id":"node:disorder%3ACOX6B1-Related_COX_Deficiency:pathophysiology:Reduced%20complex%20IV%20activity","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/COX6B1-Related_COX_Deficiency.html#pathograph","nodes":[{"id":"model:kb/disorders/COX6B1-Related_COX_Deficiency.yaml:Patient-derived fibroblasts","kind":"experimental_model","kind_label":"NAM model","label":"Patient-derived fibroblasts","description":"Arg20His patient fibroblasts, including immortalized derivatives, show impaired stable holoenzyme incorporation despite preserved total COX6B1. 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Ex-vacuo ventricular enlargement in the Arg20His brothers is a distinct imaging finding.","url":"https://dismech.monarchinitiative.org/pages/disorders/COX6B1-Related_COX_Deficiency.html#phenotype-hydrocephalus","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACOX6B1-Related_COX_Deficiency:phenotype:Hyperalaninemia","kind":"phenotype","kind_label":"Phenotype","label":"Hyperalaninemia","description":"Elevated alanine was documented in the neonatal Arg20Cys case.","url":"https://dismech.monarchinitiative.org/pages/disorders/COX6B1-Related_COX_Deficiency.html#phenotype-hyperalaninemia","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACOX6B1-Related_COX_Deficiency:phenotype:Hyperammonemia","kind":"phenotype","kind_label":"Phenotype","label":"Hyperammonemia","description":"Hyperammonemia was documented during neonatal metabolic decompensation in the Arg20Cys infant.","url":"https://dismech.monarchinitiative.org/pages/disorders/COX6B1-Related_COX_Deficiency.html#phenotype-hyperammonemia","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACOX6B1-Related_COX_Deficiency:phenotype:Hypertrophic%20cardiomyopathy","kind":"phenotype","kind_label":"Phenotype","label":"Hypertrophic cardiomyopathy","description":"The Arg20Cys patient developed hypertrophic obstructive cardiomyopathy. 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The selective vulnerability of these cells to TMEM126A deficiency remains unresolved; general mitochondrial optic-neuropathy models provide context rather than a gene-specific explanation.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Recessive_Optic_Atrophy_OPA7_Type.html#pathophysiology-retinal-ganglion-cell-degeneration","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Autosomal_Recessive_Optic_Atrophy_OPA7_Type.yaml:Patient-derived fibroblasts carrying p.Arg55Ter","source_id":"model:kb/disorders/Autosomal_Recessive_Optic_Atrophy_OPA7_Type.yaml:Patient-derived fibroblasts carrying p.Arg55Ter","target_id":"node:disorder%3AAutosomal_Recessive_Optic_Atrophy_OPA7_Type:pathophysiology:Complex%20I%20Deficiency","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Partially Recapitulates","directed":false,"relationship":"PARTIALLY_RECAPITULATES","fidelity":"NOT_SPECIFIED","causal_link_type":null,"causal_link_type_label":null,"description":"The two patient fibroblast cultures differ in whether they show a respiratory-chain defect.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AAutosomal_Recessive_Optic_Atrophy_OPA7_Type:6:0","source_id":"node:disorder%3AAutosomal_Recessive_Optic_Atrophy_OPA7_Type:pathophysiology:Complex%20I%20Deficiency","target_id":"node:disorder%3AAutosomal_Recessive_Optic_Atrophy_OPA7_Type:pathophysiology:Retinal%20Ganglion%20Cell%20Degeneration","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[6].downstream[0]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"The step from a ubiquitous enzyme deficiency to a cell-type-restricted degeneration is exactly what is not explained for this disease, so the intermediates are recorded as unknown rather than asserted.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3AAutosomal_Recessive_Optic_Atrophy_OPA7_Type:5:0","source_id":"node:disorder%3AAutosomal_Recessive_Optic_Atrophy_OPA7_Type:pathophysiology:Impaired%20Complex%20I%20Assembly","target_id":"node:disorder%3AAutosomal_Recessive_Optic_Atrophy_OPA7_Type:pathophysiology:Complex%20I%20Deficiency","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[5].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Reduced abundance of assembled enzyme lowers measured complex I activity, although residual active enzyme remains.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0}]}}],"mechanism_names":["Complex I Deficiency"],"relationships":["Partially Recapitulates"],"fidelities":["Not Specified"],"biological_scales":["Molecular"],"system_context_sources":["Linked mechanism biological scale"],"modeled_system_labels":["Molecular"],"biological_process_terms":[],"biological_processes":[],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":["Respiratory-chain function in patient III6 family 1","Complex I activity in patient V1 family 2"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"url:https://pmc.ncbi.nlm.nih.gov/articles/PMC2667974/","reference_url":null,"reference_title":"TMEM126A, Encoding a Mitochondrial Protein, Is Mutated in Autosomal-Recessive Nonsyndromic Optic Atrophy - 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The disease's burden is in brain and liver, and the rescue says nothing about whether restoring MICOS13 in those organs, or at a clinically reachable time point, would help.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0006119","label":"oxidative phosphorylation","display_label":"oxidative phosphorylation","url":"http://purl.obolibrary.org/obo/GO_0006119"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Mitochondrial respiratory chain complex activity after wild-type MICOS13 expression","description":null,"target":"Combined Respiratory Chain Deficiency","direction":"RESTORED","interpretation":"Restoration on complementation establishes that the absence of MICOS13 is the cause of the respiratory deficiency, not a bystander.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:32749073","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/32749073","reference_title":"A novel homozygous variant in MICOS13/QIL1 causes hepato-encephalopathy with mitochondrial DNA depletion syndrome.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Stable expression of a wild-type MICOS13 cDNA in the patients fibroblasts using a lentivirus system rescued mitochondrial respiratory chain complex deficiencies.","explanation":"The rescue result."}],"notes":null}],"evidence":[{"reference":"PMID:32749073","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/32749073","reference_title":"A novel homozygous variant in MICOS13/QIL1 causes hepato-encephalopathy with mitochondrial DNA depletion syndrome.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Stable expression of a wild-type MICOS13 cDNA in the patients fibroblasts using a lentivirus system rescued mitochondrial respiratory chain complex deficiencies.","explanation":"The rescue result."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Combined_Oxidative_Phosphorylation_Defect_Type_37","model_node_id":"model:kb/disorders/Combined_Oxidative_Phosphorylation_Defect_Type_37.yaml:Patient-derived fibroblasts with lentiviral MICOS13 rescue","focus_node_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Defect_Type_37:pathophysiology:Combined%20Respiratory%20Chain%20Deficiency","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Oxidative_Phosphorylation_Defect_Type_37.html#pathograph","nodes":[{"id":"model:kb/disorders/Combined_Oxidative_Phosphorylation_Defect_Type_37.yaml:Patient-derived fibroblasts with lentiviral MICOS13 rescue","kind":"experimental_model","kind_label":"NAM model","label":"Patient-derived fibroblasts with lentiviral MICOS13 rescue","description":"Fibroblasts from the second patient, used both to characterise the defect and, with a wild-type MICOS13 cDNA restored by lentivirus, to test causation.\nThis is the experiment that makes the entry's central causal claim more than an association. 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Fatal in the first reported patient.","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Oxidative_Phosphorylation_Defect_Type_37.html#pathophysiology-lactic-acidosis-and-hepato-encephalopathy","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Defect_Type_37:pathophysiology:Loss%20of%20Cristae%20Junctions%20and%20Inner%20Membrane%20Contact%20Sites","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Loss of Cristae Junctions and Inner Membrane Contact Sites","description":"The structural lesion of the disease. Cristae junctions are the narrow necks that connect each crista to the inner boundary membrane, and they do two things: they hold the folded surface area on which respiratory complexes are concentrated, and they partition the intermembrane space so that the crista lumen is a distinct compartment. Contact sites link the inner membrane to the outer.\nLosing them is therefore not simply a morphological finding. It removes the geometry that makes oxidative phosphorylation efficient, which is why an architectural defect presents as a bioenergetic disease.","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Oxidative_Phosphorylation_Defect_Type_37.html#pathophysiology-loss-of-cristae-junctions-and-inner-membrane-contact-sites","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Combined_Oxidative_Phosphorylation_Defect_Type_37.yaml:Patient-derived fibroblasts with lentiviral MICOS13 rescue","source_id":"model:kb/disorders/Combined_Oxidative_Phosphorylation_Defect_Type_37.yaml:Patient-derived fibroblasts with lentiviral MICOS13 rescue","target_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Defect_Type_37:pathophysiology:Combined%20Respiratory%20Chain%20Deficiency","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Rescues","directed":false,"relationship":"RESCUES","fidelity":"HIGH","causal_link_type":null,"causal_link_type_label":null,"description":"Restoring MICOS13 restores respiratory chain complex activity in the patient's own cells.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ACombined_Oxidative_Phosphorylation_Defect_Type_37:3:0","source_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Defect_Type_37:pathophysiology:Combined%20Respiratory%20Chain%20Deficiency","target_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Defect_Type_37:pathophysiology:Lactic%20Acidosis%20and%20Hepato-Encephalopathy","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[3].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Impaired ATP production in the two most oxidative organs, with lactate accumulating as glycolysis substitutes.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ACombined_Oxidative_Phosphorylation_Defect_Type_37:2:0","source_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Defect_Type_37:pathophysiology:Loss%20of%20Cristae%20Junctions%20and%20Inner%20Membrane%20Contact%20Sites","target_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Defect_Type_37:pathophysiology:Combined%20Respiratory%20Chain%20Deficiency","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"The complexes are intact but the membrane they work in is not.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0}]}},{"target":"Failure of MICOS Complex Assembly","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Oxidative_Phosphorylation_Defect_Type_37.html#pathophysiology-failure-of-micos-complex-assembly","relationship":"MEASURES","relationship_label":"Measures","fidelity":"HIGH","fidelity_label":"High","description":"The system in which protein loss and reduced cristae number were demonstrated.","limitations":"Cristae number here was assessed in fibroblasts rather than in an affected organ. 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MIC60 is the core of the other MICOS subcomplex, so what fails is one arm of the complex rather than the complex as a whole - which is a more specific claim than \"MICOS is disrupted\" and is consistent with the MIC10-MIC26-MIC27-QIL1 subcomplex loss reported independently.","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Oxidative_Phosphorylation_Defect_Type_37.html#pathophysiology-failure-of-micos-complex-assembly","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Defect_Type_37:pathophysiology:Biallelic%20MICOS13%20Loss-of-Function","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Biallelic MICOS13 Loss-of-Function","description":"Several reported alleles, all loss of function and all removing the protein rather than altering it. 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assembly.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ACombined_Oxidative_Phosphorylation_Defect_Type_37:1:0","source_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Defect_Type_37:pathophysiology:Failure%20of%20MICOS%20Complex%20Assembly","target_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Defect_Type_37:pathophysiology:Loss%20of%20Cristae%20Junctions%20and%20Inner%20Membrane%20Contact%20Sites","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"The subcomplex that fails to form is the one that shapes cristae junctions.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0}]}}],"mechanism_names":["Combined Respiratory Chain Deficiency","Failure of MICOS Complex Assembly"],"relationships":["Rescues","Measures"],"fidelities":["High"],"biological_scales":["Cellular","Molecular"],"system_context_sources":["Linked mechanism biological scale"],"modeled_system_labels":["Cellular","Molecular"],"biological_process_terms":[{"id":"GO:0006119","label":"oxidative phosphorylation","display_label":"oxidative phosphorylation","url":"http://purl.obolibrary.org/obo/GO_0006119"},{"id":"GO:0042407","label":"cristae formation","display_label":"cristae formation","url":"http://purl.obolibrary.org/obo/GO_0042407"}],"biological_processes":["oxidative phosphorylation","cristae formation"],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":["Mitochondrial respiratory chain complex activity after wild-type MICOS13 expression","MICOS13 protein level and cristae number in patient fibroblast mitochondria"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:32749073","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/32749073","reference_title":"A novel homozygous variant in MICOS13/QIL1 causes hepato-encephalopathy with mitochondrial DNA depletion syndrome.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We found loss of MICOS13 protein and fewer cristae structures in the mitochondria of fibroblasts derived from the patient.","explanation":"Establishes that the patient's fibroblasts carry the molecular and structural defect, which is what makes them an informative model of it."},{"reference":"PMID:32749073","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/32749073","reference_title":"A novel homozygous variant in MICOS13/QIL1 causes hepato-encephalopathy with mitochondrial DNA depletion syndrome.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Stable expression of a wild-type MICOS13 cDNA in the patients fibroblasts using a lentivirus system rescued mitochondrial respiratory chain complex deficiencies.","explanation":"The rescue result."}],"evidence_text":["We found loss of MICOS13 protein and fewer cristae structures in the mitochondria of fibroblasts derived from the patient.","Stable expression of a wild-type MICOS13 cDNA in the patients fibroblasts using a lentivirus system rescued mitochondrial respiratory chain complex deficiencies.","Establishes that the patient's fibroblasts carry the molecular and structural defect, which is what makes them an informative model of it.","The rescue result."],"evidence_status":"Evidence recorded","metadata_completeness":30,"metadata_present":["Model category","Modeled mechanism","Evidence"],"metadata_missing":["NAMO class","Organism","Anatomy","Cell type","Cell source","Culture system","Publication"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Combined_Oxidative_Phosphorylation_Defect_Type_37.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Combined_Oxidative_Phosphorylation_Defect_Type_37.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Oxidative_Phosphorylation_Defect_Type_37.html#experimental-model-patient-derived-fibroblasts-with-lentiviral-micos13-rescue","source_anchor":"experimental-model-patient-derived-fibroblasts-with-lentiviral-micos13-rescue"},{"id":"model:kb/disorders/Combined_Immunodeficiency_Due_To_GINS1_Deficiency.yaml:Patient-derived fibroblasts with wild-type GINS1 rescue","name":"Patient-derived fibroblasts with wild-type GINS1 rescue","description":"The system that carries most of this entry's mechanistic weight. Primary fibroblasts from affected individuals reproduce the cellular phenotype - impaired GINS complex assembly, basal replication stress, impaired checkpoint signalling, defective cell cycle control and genomic instability - and re-expressing wild-type GINS1 reverses it. The rescue arm is what converts a set of correlated abnormalities in patient cells into a causal claim about GINS1.\n","notes":null,"context_id":"disorder:Combined_Immunodeficiency_Due_To_GINS1_Deficiency","context_kind":"Disorder","disease_name":"Combined Immunodeficiency Due To GINS1 Deficiency","disease_synonyms":["IMD55","immunodeficiency 55","CID due to GINS1 deficiency","GINS1 deficiency","combined immunodeficiency with intrauterine growth retardation-NK cell deficiency-neutropenia"],"disease_term":{"id":"MONDO:0044725","label":"combined immunodeficiency due to GINS1 deficiency","display_label":"combined immunodeficiency due to GINS1 deficiency","url":"http://purl.obolibrary.org/obo/MONDO_0044725"},"experimental_model_type":"PRIMARY_CELL_CULTURE","experimental_model_type_label":"Primary-cell culture","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":null,"source_category":"Primary / biopsy-derived","culture_system":null,"publication":"PMID:28414293","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/28414293","mechanisms":[{"target":"Impaired GINS/CMG Replicative Helicase Assembly","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Immunodeficiency_Due_To_GINS1_Deficiency.html#pathophysiology-impaired-gins-cmg-replicative-helicase-assembly","relationship":"RECAPITULATES","relationship_label":"Recapitulates","fidelity":"HIGH","fidelity_label":"High","description":"Patient cells carrying the actual disease genotypes show the assembly defect directly.\n","limitations":"Fibroblasts are not a haematopoietic lineage, so the model speaks to the general replication defect and to the growth arm, not to the marrow maturation blockade that defines the disease clinically. Cultured fibroblasts also proliferate under conditions unlike those of a differentiating progenitor in vivo.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0140529","label":"CMG complex assembly","display_label":"CMG complex assembly","url":"http://purl.obolibrary.org/obo/GO_0140529"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"GINS complex assembly","description":null,"target":"Impaired GINS/CMG Replicative Helicase Assembly","direction":"DECREASED","interpretation":"Direct measurement of the molecular defect in patient cells.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:28414293","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/28414293","reference_title":"Inherited GINS1 deficiency underlies growth retardation along with neutropenia and NK cell deficiency.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The patients' fibroblasts displayed impaired GINS complex assembly, basal replication stress, impaired checkpoint signaling, defective cell cycle control, and genomic instability, which was rescued by WT GINS1.","explanation":"Reports impaired GINS complex assembly in patient fibroblasts."}],"notes":null},{"name":"Residual GINS1 activity","description":null,"target":"Impaired GINS/CMG Replicative Helicase Assembly","direction":"DECREASED","interpretation":"Quantifies how much function the hypomorphic alleles retain, which is the disease-relevant quantity.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:28414293","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/28414293","reference_title":"Inherited GINS1 deficiency underlies growth retardation along with neutropenia and NK cell deficiency.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The residual levels of GINS1 activity reached 3% to 16% in patients' cells, depending on their GINS1 genotype, and correlated with the severity of growth retardation and the in vitro cellular phenotype.","explanation":"Reports the residual activity range and its genotype dependence."}],"notes":null}],"evidence":[{"reference":"PMID:28414293","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/28414293","reference_title":"Inherited GINS1 deficiency underlies growth retardation along with neutropenia and NK cell deficiency.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The patients' fibroblasts displayed impaired GINS complex assembly, basal replication stress, impaired checkpoint signaling, defective cell cycle control, and genomic instability, which was rescued by WT GINS1.","explanation":"Reports impaired GINS complex assembly in patient fibroblasts."},{"reference":"PMID:28414293","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/28414293","reference_title":"Inherited GINS1 deficiency underlies growth retardation along with neutropenia and NK cell deficiency.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The residual levels of GINS1 activity reached 3% to 16% in patients' cells, depending on their GINS1 genotype, and correlated with the severity of growth retardation and the in vitro cellular phenotype.","explanation":"Reports the residual activity range and its genotype dependence."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Combined_Immunodeficiency_Due_To_GINS1_Deficiency","model_node_id":"model:kb/disorders/Combined_Immunodeficiency_Due_To_GINS1_Deficiency.yaml:Patient-derived fibroblasts with wild-type GINS1 rescue","focus_node_id":"node:disorder%3ACombined_Immunodeficiency_Due_To_GINS1_Deficiency:pathophysiology:Impaired%20GINS%2FCMG%20Replicative%20Helicase%20Assembly","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Immunodeficiency_Due_To_GINS1_Deficiency.html#pathograph","nodes":[{"id":"model:kb/disorders/Combined_Immunodeficiency_Due_To_GINS1_Deficiency.yaml:Patient-derived fibroblasts with wild-type GINS1 rescue","kind":"experimental_model","kind_label":"NAM model","label":"Patient-derived fibroblasts with wild-type GINS1 rescue","description":"The system that carries most of this entry's mechanistic weight. 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Because GINS is one of the three modules of the CMG helicase, defective GINS assembly translates directly into reduced replicative helicase availability at origins.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Immunodeficiency_Due_To_GINS1_Deficiency.html#pathophysiology-impaired-gins-cmg-replicative-helicase-assembly","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACombined_Immunodeficiency_Due_To_GINS1_Deficiency:pathophysiology:Biallelic%20Hypomorphic%20GINS1%20Variants","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Biallelic Hypomorphic GINS1 Variants","description":"Compound heterozygous GINS1 variants reduce, but never abolish, functional GINS1 protein. Complete loss is not a possible disease state: homozygous null mutations of GINS component-encoding genes are embryonic lethal in mice, so every viable patient genotype is a partial one.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Immunodeficiency_Due_To_GINS1_Deficiency.html#pathophysiology-biallelic-hypomorphic-gins1-variants","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACombined_Immunodeficiency_Due_To_GINS1_Deficiency:pathophysiology:Replication%20Stress%20with%20Impaired%20Checkpoint%20Signaling","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Replication Stress with Impaired Checkpoint Signaling","description":"Patient cells carry basal replication stress together with impaired checkpoint signalling. The combination matters: a cell under replication stress that can still signal the checkpoint arrests and repairs, whereas one that cannot signal proceeds through the cycle carrying unresolved replication problems. It is this second state that converts a quantitative shortage of helicase into genomic damage.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Immunodeficiency_Due_To_GINS1_Deficiency.html#pathophysiology-replication-stress-with-impaired-checkpoint-signaling","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Combined_Immunodeficiency_Due_To_GINS1_Deficiency.yaml:Patient-derived fibroblasts with wild-type GINS1 rescue","source_id":"model:kb/disorders/Combined_Immunodeficiency_Due_To_GINS1_Deficiency.yaml:Patient-derived fibroblasts with wild-type GINS1 rescue","target_id":"node:disorder%3ACombined_Immunodeficiency_Due_To_GINS1_Deficiency:pathophysiology:Impaired%20GINS%2FCMG%20Replicative%20Helicase%20Assembly","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"HIGH","causal_link_type":null,"causal_link_type_label":null,"description":"Patient cells carrying the actual disease genotypes show the assembly defect directly.\n","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ACombined_Immunodeficiency_Due_To_GINS1_Deficiency:0:0","source_id":"node:disorder%3ACombined_Immunodeficiency_Due_To_GINS1_Deficiency:pathophysiology:Biallelic%20Hypomorphic%20GINS1%20Variants","target_id":"node:disorder%3ACombined_Immunodeficiency_Due_To_GINS1_Deficiency:pathophysiology:Impaired%20GINS%2FCMG%20Replicative%20Helicase%20Assembly","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[0]","label":"Causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":null,"causal_link_type_label":null,"description":"Reduced GINS1 protein cannot support normal assembly of the GINS complex.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ACombined_Immunodeficiency_Due_To_GINS1_Deficiency:1:0","source_id":"node:disorder%3ACombined_Immunodeficiency_Due_To_GINS1_Deficiency:pathophysiology:Impaired%20GINS%2FCMG%20Replicative%20Helicase%20Assembly","target_id":"node:disorder%3ACombined_Immunodeficiency_Due_To_GINS1_Deficiency:pathophysiology:Replication%20Stress%20with%20Impaired%20Checkpoint%20Signaling","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[0]","label":"Causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":null,"causal_link_type_label":null,"description":"Reduced CMG helicase availability stalls and slows replication forks.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0}]}},{"target":"Defective Cell Cycle Control and Genomic Instability","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Immunodeficiency_Due_To_GINS1_Deficiency.html#pathophysiology-defective-cell-cycle-control-and-genomic-instability","relationship":"RESCUES","relationship_label":"Rescues","fidelity":"HIGH","fidelity_label":"High","description":"Re-expression of wild-type GINS1 reverses the cellular phenotype, which is the causal test rather than an observation.\n","limitations":"Rescue is by transgenic overexpression rather than by correcting the endogenous alleles, so it establishes sufficiency of wild-type GINS1 but not the dose at which the phenotype would resolve.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0000075","label":"cell cycle checkpoint signaling","display_label":"cell cycle checkpoint signaling","url":"http://purl.obolibrary.org/obo/GO_0000075"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Cell cycle control and genomic instability","description":null,"target":"Defective Cell Cycle Control and Genomic Instability","direction":"RESTORED","interpretation":"The rescue arm; reversal on wild-type re-expression.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:28414293","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/28414293","reference_title":"Inherited GINS1 deficiency underlies growth retardation along with neutropenia and NK cell deficiency.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The patients' fibroblasts displayed impaired GINS complex assembly, basal replication stress, impaired checkpoint signaling, defective cell cycle control, and genomic instability, which was rescued by WT GINS1.","explanation":"The same sentence reports the defects and their reversal by wild-type GINS1; the rescue clause is what this readout records.\n"}],"notes":null}],"evidence":[{"reference":"PMID:28414293","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/28414293","reference_title":"Inherited GINS1 deficiency underlies growth retardation along with neutropenia and NK cell deficiency.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The patients' fibroblasts displayed impaired GINS complex assembly, basal replication stress, impaired checkpoint signaling, defective cell cycle control, and genomic instability, which was rescued by WT GINS1.","explanation":"The same sentence reports the defects and their reversal by wild-type GINS1; the rescue clause is what this readout records.\n"}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Combined_Immunodeficiency_Due_To_GINS1_Deficiency","model_node_id":"model:kb/disorders/Combined_Immunodeficiency_Due_To_GINS1_Deficiency.yaml:Patient-derived fibroblasts with wild-type GINS1 rescue","focus_node_id":"node:disorder%3ACombined_Immunodeficiency_Due_To_GINS1_Deficiency:pathophysiology:Defective%20Cell%20Cycle%20Control%20and%20Genomic%20Instability","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Immunodeficiency_Due_To_GINS1_Deficiency.html#pathograph","nodes":[{"id":"model:kb/disorders/Combined_Immunodeficiency_Due_To_GINS1_Deficiency.yaml:Patient-derived fibroblasts with wild-type GINS1 rescue","kind":"experimental_model","kind_label":"NAM model","label":"Patient-derived fibroblasts with wild-type GINS1 rescue","description":"The system that carries most of this entry's mechanistic weight. 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The functional cost of this state is borne disproportionately by cell types that must undergo rapid proliferative expansion, which is the link to both the growth and the haematopoietic arms of the disease.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Immunodeficiency_Due_To_GINS1_Deficiency.html#pathophysiology-defective-cell-cycle-control-and-genomic-instability","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACombined_Immunodeficiency_Due_To_GINS1_Deficiency:pathophysiology:Bone%20Marrow%20Maturation%20Blockade%20of%20Granulocyte%20and%20NK%20Lineages","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Bone Marrow Maturation Blockade of Granulocyte and NK Lineages","description":"The neutropenia and the NK cell deficiency are both central, not peripheral: the source locates the defect as a blockade in the bone marrow. This is the entry's defining lesion, and the co-occurrence of these two particular lineages is explicitly noted as unusual among primary immunodeficiencies and bone marrow failures.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Immunodeficiency_Due_To_GINS1_Deficiency.html#pathophysiology-bone-marrow-maturation-blockade-of-granulocyte-and-nk-lineages","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACombined_Immunodeficiency_Due_To_GINS1_Deficiency:phenotype:Glaucoma","kind":"phenotype","kind_label":"Phenotype","label":"Glaucoma","description":"Reported in more than one unrelated individual, including congenital unilateral glaucoma with secondary high myopia in the 2026 proband. The reviewing authors flag this as a possible expansion of the phenotype rather than an established core feature, and this entry follows that reading - it is recorded as an emerging association, not as part of the defining triad.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Immunodeficiency_Due_To_GINS1_Deficiency.html#phenotype-glaucoma","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACombined_Immunodeficiency_Due_To_GINS1_Deficiency:phenotype:Mild%20Facial%20Dysmorphism","kind":"phenotype","kind_label":"Phenotype","label":"Mild Facial Dysmorphism","description":"Reported in the patients alongside the growth retardation; not characterised into a recognisable gestalt in the source.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Immunodeficiency_Due_To_GINS1_Deficiency.html#phenotype-mild-facial-dysmorphism","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACombined_Immunodeficiency_Due_To_GINS1_Deficiency:phenotype:Reduced%20CD8-Positive%20T%20Cell%20Count%20in%20Early%20Childhood","kind":"phenotype","kind_label":"Phenotype","label":"Reduced CD8-Positive T Cell Count in Early Childhood","description":"In the two patients tested during the first three years of life, blood T cell counts were low, especially CD8+ T cells. This is the observation that most supports the \"combined\" in the disease name, and it is age-limited: outside that window most patients had low or normal T and B lymphocyte numbers.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Immunodeficiency_Due_To_GINS1_Deficiency.html#phenotype-reduced-cd8-positive-t-cell-count-in-early-childhood","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACombined_Immunodeficiency_Due_To_GINS1_Deficiency:pathophysiology:Replication%20Stress%20with%20Impaired%20Checkpoint%20Signaling","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Replication Stress with Impaired Checkpoint Signaling","description":"Patient cells carry basal replication stress together with impaired checkpoint signalling. The combination matters: a cell under replication stress that can still signal the checkpoint arrests and repairs, whereas one that cannot signal proceeds through the cycle carrying unresolved replication problems. It is this second state that converts a quantitative shortage of helicase into genomic damage.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Immunodeficiency_Due_To_GINS1_Deficiency.html#pathophysiology-replication-stress-with-impaired-checkpoint-signaling","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACombined_Immunodeficiency_Due_To_GINS1_Deficiency:pathophysiology:Restricted%20Somatic%20Growth","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Restricted Somatic Growth","description":"Growth restriction begins in utero and in most patients continues after birth. Unlike the immunological arm, this arm is dose-dependent: severity tracked the residual GINS1 activity measured in patient cells. 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It is the finding that points the differential at the translation apparatus rather than at an assembly factor or a structural subunit of one complex, and it is what a curator or clinician should look for in the enzymology report.","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Oxidative_Phosphorylation_Deficiency_51.html#pathophysiology-combined-respiratory-chain-deficiency-with-complex-ii-spared","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_51:pathophysiology:Reduced%20Mitochondrial%20Respiratory%20Capacity%20and%20ATP%20Deficit","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced Mitochondrial Respiratory Capacity and ATP Deficit","description":"High-resolution respirometry in patient fibroblasts shows a modest fall in basal respiration and a marked fall in maximal (uncoupled) respiratory capacity; the index patient also had reduced ATP biosynthesis. 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No disease-specific neuronal phenotype has yet been reported from them, so this is curated as an available resource, not as a source of mechanistic findings.","url":"https://dismech.monarchinitiative.org/pages/disorders/Developmental_And_Epileptic_Encephalopathy_46.html#experimental-model-patient-derived-grin2d-dee-ipsc-line","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ADevelopmental_And_Epileptic_Encephalopathy_46:pathophysiology:GRIN2D%20Missense%20Variant%20Altering%20the%20GluN2D%20NMDA%20Receptor%20Subunit","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"GRIN2D Missense Variant Altering the GluN2D NMDA Receptor Subunit","description":"The initiating lesion is a heterozygous, usually de novo, missense variant in GRIN2D that substitutes a single residue in the GluN2D subunit of the NMDA receptor. Reported disease alleles cluster in the M3 gating helix and the adjacent pre-M1 and transmembrane regions, with a smaller set in the intracellular carboxyl-terminal domain. Null (protein-truncating) GRIN2D alleles have not been reported in affected individuals, so unlike GRIN2B this disorder is not a haploinsufficiency syndrome.","url":"https://dismech.monarchinitiative.org/pages/disorders/Developmental_And_Epileptic_Encephalopathy_46.html#pathophysiology-grin2d-missense-variant-altering-the-glun2d-nmda-receptor-subunit","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ADevelopmental_And_Epileptic_Encephalopathy_46:pathophysiology:NMDA%20Receptor%20Gain-of-Function","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"NMDA Receptor Gain-of-Function","description":"In the gain-of-function branch the mutant GluN2D-containing receptor opens more readily and stays open longer. For the recurrent p.Val667Ile allele this is a combination of roughly two-fold higher glutamate and glycine potency, a roughly six-fold increase in channel open probability, reduced inhibition by endogenous extracellular protons, and a prolonged deactivation time course after glutamate is removed — the last of which lengthens the synaptic response itself. Other alleles reach the same endpoint by different combinations: p.Leu670Phe and p.Ala678Asp raise open probability from a wild-type value near 0.007 to 0.36 and 0.20 respectively, and p.Leu670Phe slows deactivation and increases charge transfer.","url":"https://dismech.monarchinitiative.org/pages/disorders/Developmental_And_Epileptic_Encephalopathy_46.html#pathophysiology-nmda-receptor-gain-of-function","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ADevelopmental_And_Epileptic_Encephalopathy_46:pathophysiology:Reduced%20GluN2D%20Receptor%20Surface%20Expression","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced GluN2D Receptor Surface Expression","description":"A consequence shared across the tested GRIN2D disease alleles is reduced delivery of GluN2D-containing receptors to the plasma membrane. This is a distinct axis from channel gating: a variant may simultaneously reduce the number of surface receptors and increase the activity of each one, so \"reduced surface expression\" must not be read as net receptor loss of function. Where reduced surface expression is not offset by increased per-receptor activity it lowers current amplitude.","url":"https://dismech.monarchinitiative.org/pages/disorders/Developmental_And_Epileptic_Encephalopathy_46.html#pathophysiology-reduced-glun2d-receptor-surface-expression","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Developmental_And_Epileptic_Encephalopathy_46.yaml:Patient-derived GRIN2D DEE iPSC line","source_id":"model:kb/disorders/Developmental_And_Epileptic_Encephalopathy_46.yaml:Patient-derived GRIN2D DEE iPSC line","target_id":"node:disorder%3ADevelopmental_And_Epileptic_Encephalopathy_46:pathophysiology:GRIN2D%20Missense%20Variant%20Altering%20the%20GluN2D%20NMDA%20Receptor%20Subunit","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Perturbs","directed":false,"relationship":"PERTURBS","fidelity":"UNKNOWN","causal_link_type":null,"causal_link_type_label":null,"description":"The line carries the patient's own gain-of-function allele in a human genetic background.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ADevelopmental_And_Epileptic_Encephalopathy_46:0:0","source_id":"node:disorder%3ADevelopmental_And_Epileptic_Encephalopathy_46:pathophysiology:GRIN2D%20Missense%20Variant%20Altering%20the%20GluN2D%20NMDA%20Receptor%20Subunit","target_id":"node:disorder%3ADevelopmental_And_Epileptic_Encephalopathy_46:pathophysiology:NMDA%20Receptor%20Gain-of-Function","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"A subset of missense substitutions, of which the recurrent M3-domain p.Val667Ile allele is the best characterised, increases NMDA receptor channel activity.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ADevelopmental_And_Epileptic_Encephalopathy_46:0:1","source_id":"node:disorder%3ADevelopmental_And_Epileptic_Encephalopathy_46:pathophysiology:GRIN2D%20Missense%20Variant%20Altering%20the%20GluN2D%20NMDA%20Receptor%20Subunit","target_id":"node:disorder%3ADevelopmental_And_Epileptic_Encephalopathy_46:pathophysiology:Reduced%20GluN2D%20Receptor%20Surface%20Expression","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[1]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Independently of their effect on channel gating, GRIN2D missense substitutions impair delivery of assembled receptors to the cell surface.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1}]}}],"mechanism_names":["GRIN2D Missense Variant Altering the GluN2D NMDA Receptor Subunit"],"relationships":["Perturbs"],"fidelities":["Unknown"],"biological_scales":["Molecular"],"system_context_sources":["Linked mechanism cell type","Linked mechanism biological scale"],"modeled_system_labels":["glutamatergic neuron","Molecular"],"biological_process_terms":[],"biological_processes":[],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":[],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:33482465","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33482465","reference_title":"Reprogramming of two induced pluripotent stem cell lines from a heterozygous GRIN2D developmental and epileptic encephalopathy (DEE) patient (BGUi011-A) and from a healthy family relative (BGUi012-A).","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We report the generation of induced pluripotent stem cell (iPSC) lines from a GRIN2D-developmental and epileptic encephalopathy (DEE) patient, carrying a de novo c.1999G>A heterozygous pathogenic variant, and his healthy parent.","explanation":"Documents the existence and genotype of the patient-derived line."}],"evidence_text":["We report the generation of induced pluripotent stem cell (iPSC) lines from a GRIN2D-developmental and epileptic encephalopathy (DEE) patient, carrying a de novo c.1999G>A heterozygous pathogenic variant, and his healthy parent.","Documents the existence and genotype of the patient-derived line."],"evidence_status":"Evidence recorded","metadata_completeness":40,"metadata_present":["Model category","Cell type","Modeled mechanism","Evidence"],"metadata_missing":["NAMO class","Organism","Anatomy","Cell source","Culture system","Publication"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Developmental_And_Epileptic_Encephalopathy_46.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Developmental_And_Epileptic_Encephalopathy_46.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Developmental_And_Epileptic_Encephalopathy_46.html#experimental-model-patient-derived-grin2d-dee-ipsc-line","source_anchor":"experimental-model-patient-derived-grin2d-dee-ipsc-line"},{"id":"model:kb/disorders/Sick_Sinus_Syndrome_2_Autosomal_Dominant.yaml:Patient-derived hiPSC lines carrying a heterozygous and a homozygous HCN4 variant (UKMi009-A, UKMi011-A)","name":"Patient-derived hiPSC lines carrying a heterozygous and a homozygous HCN4 variant (UKMi009-A, UKMi011-A)","description":"Two human induced pluripotent stem cell lines reprogrammed from members of a consanguineous family with sinus node dysfunction, one carrying the familial HCN4 variant heterozygously and the other homozygously. The pair is a gene-dose series in the patients' own genetic background and at the native locus, which is the closest available human substrate for the SSS2 lesion. As published, the lines are characterised only for pluripotency (karyotype, marker expression, three-germ-layer differentiation); no cardiomyocyte electrophysiology is reported, so nothing yet establishes that they reproduce the funny-current deficit.","notes":null,"context_id":"disorder:Sick_Sinus_Syndrome_2_Autosomal_Dominant","context_kind":"Disorder","disease_name":"Sick Sinus Syndrome 2, Autosomal Dominant","disease_synonyms":["SSS2","HCN4 sick sinus syndrome","sick sinus syndrome caused by mutation in HCN4","HCN4-related sinus node dysfunction","familial sinus bradycardia, HCN4-related"],"disease_term":{"id":"MONDO:0008102","label":"sick sinus syndrome 2, autosomal dominant","display_label":"sick sinus syndrome 2, autosomal dominant","url":"http://purl.obolibrary.org/obo/MONDO_0008102"},"experimental_model_type":"IPSC_DERIVED_MODEL","experimental_model_type_label":"iPSC-derived model","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},"organism_label":"Homo sapiens","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[{"id":"UBERON:0002351","label":"sinoatrial node","display_label":"sinoatrial node","url":"http://purl.obolibrary.org/obo/UBERON_0002351"}],"linked_anatomy_labels":["sinoatrial node"],"anatomy":[{"id":"UBERON:0002351","label":"sinoatrial node","display_label":"sinoatrial node","url":"http://purl.obolibrary.org/obo/UBERON_0002351"}],"anatomy_labels":["sinoatrial node"],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[{"id":"CL:1000477","label":"cardiac pacemaker cell of sinoatrial node","display_label":"cardiac pacemaker cell of sinoatrial node","url":"http://purl.obolibrary.org/obo/CL_1000477"}],"linked_cell_type_labels":["cardiac pacemaker cell of sinoatrial node"],"cell_types":[{"id":"CL:1000477","label":"cardiac pacemaker cell of sinoatrial node","display_label":"cardiac pacemaker cell of sinoatrial node","url":"http://purl.obolibrary.org/obo/CL_1000477"}],"cell_type_labels":["cardiac pacemaker cell of sinoatrial node"],"conditions":[],"cell_source":"Reprogrammed somatic cells from two members of a consanguineous family with inherited sinus node dysfunction.","source_category":"iPSC-derived","culture_system":null,"publication":"PMID:40414080","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40414080","mechanisms":[{"target":"HCN4 Loss-of-Function Variant","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Sick_Sinus_Syndrome_2,_Autosomal_Dominant.html#pathophysiology-hcn4-loss-of-function-variant","relationship":"PERTURBS","relationship_label":"Perturbs","fidelity":"UNKNOWN","fidelity_label":"Unknown","description":"The lines carry the family's own HCN4 variant at the endogenous locus in one and two copies, instantiating the genetic lesion of this node as a dose series rather than as an overexpressed construct.","limitations":"The family is consanguineous and the report does not say which members are affected, so it is not established that the heterozygous carrier has the disease; in a consanguineous pedigree segregating a homozygous allele the heterozygote may well be an unaffected carrier. Neither line is therefore known to instantiate the dominant heterozygous genotype of SSS2, and the homozygous state has no counterpart in it at all. The report also does not characterise the variant as loss-of-function: the link to this node rests on the gene, not on a demonstrated functional consequence. The publication reports pluripotency characterisation alone, with no cardiomyocyte differentiation, no I_f recording and no beating rate, so the functional fidelity of the model is untested rather than moderate or high.","biological_scale":"MOLECULAR","anatomy":[{"id":"UBERON:0002351","label":"sinoatrial node","display_label":"sinoatrial node","url":"http://purl.obolibrary.org/obo/UBERON_0002351"}],"cell_types":[{"id":"CL:1000477","label":"cardiac pacemaker cell of sinoatrial node","display_label":"cardiac pacemaker cell of sinoatrial node","url":"http://purl.obolibrary.org/obo/CL_1000477"}],"biological_processes":[],"pathways":[],"genes":[{"id":"hgnc:16882","label":"HCN4","display_label":"HCN4","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/16882"}],"chemicals":[],"readouts":[],"evidence":[{"reference":"PMID:40414080","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40414080","reference_title":"Generation of human induced pluripotent stem cell (hiPSC) lines (UKMi009-A and UKMi011-A) harboring a homozygous and heterozygous HCN4 variant from a family with inherited sinus node dysfunction (SND).","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Here, we generated two hiPSC lines from a consanguineous family with SND where the HCN4 variant was either present in heterozygous or homozygous state.","explanation":"Establishes that the lines carry the patient HCN4 variant in a gene-dose series, which is the perturbation this link records."},{"reference":"PMID:40414080","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40414080","reference_title":"Generation of human induced pluripotent stem cell (hiPSC) lines (UKMi009-A and UKMi011-A) harboring a homozygous and heterozygous HCN4 variant from a family with inherited sinus node dysfunction (SND).","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Both cell lines exhibited normal karyotype, cell morphology, hiPSC marker expression, and differentiation into all three germ layers, confirmed by immunofluorescence staining.","explanation":"The reported characterisation stops at pluripotency, which is why the fidelity of this link is recorded as UNKNOWN rather than asserted."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Sick_Sinus_Syndrome_2_Autosomal_Dominant","model_node_id":"model:kb/disorders/Sick_Sinus_Syndrome_2_Autosomal_Dominant.yaml:Patient-derived hiPSC lines carrying a heterozygous and a homozygous HCN4 variant (UKMi009-A, UKMi011-A)","focus_node_id":"node:disorder%3ASick_Sinus_Syndrome_2_Autosomal_Dominant:pathophysiology:HCN4%20Loss-of-Function%20Variant","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Sick_Sinus_Syndrome_2,_Autosomal_Dominant.html#pathograph","nodes":[{"id":"model:kb/disorders/Sick_Sinus_Syndrome_2_Autosomal_Dominant.yaml:Patient-derived hiPSC lines carrying a heterozygous and a homozygous HCN4 variant (UKMi009-A, UKMi011-A)","kind":"experimental_model","kind_label":"NAM model","label":"Patient-derived hiPSC lines carrying a heterozygous and a homozygous HCN4 variant (UKMi009-A, UKMi011-A)","description":"Two human induced pluripotent stem cell lines reprogrammed from members of a consanguineous family with sinus node dysfunction, one carrying the familial HCN4 variant heterozygously and the other homozygously. The pair is a gene-dose series in the patients' own genetic background and at the native locus, which is the closest available human substrate for the SSS2 lesion. As published, the lines are characterised only for pluripotency (karyotype, marker expression, three-germ-layer differentiation); no cardiomyocyte electrophysiology is reported, so nothing yet establishes that they reproduce the funny-current deficit.","url":"https://dismech.monarchinitiative.org/pages/disorders/Sick_Sinus_Syndrome_2,_Autosomal_Dominant.html#experimental-model-patient-derived-hipsc-lines-carrying-a-heterozygous-and-a-homozygous-hcn4-variant-ukmi009-a-ukmi011-a","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ASick_Sinus_Syndrome_2_Autosomal_Dominant:pathophysiology:HCN4%20Loss-of-Function%20Variant","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"HCN4 Loss-of-Function Variant","description":"A heterozygous loss-of-function variant in HCN4 alters the pore-forming subunit of the cardiac pacemaker channel. Reported disease alleles cluster in three structural regions with three corresponding biophysical consequences: pore-domain missense changes (G480R, G482R) that impair channel synthesis, trafficking, and gating; C-linker and cyclic-nucleotide-binding-domain changes (S672R, K530N) that shift activation gating; and C-terminal truncations (573X, 695X) that delete the cyclic-nucleotide-binding domain. All are heterozygous, and most act dominant-negatively on wild-type subunits within the heterotetramer.","url":"https://dismech.monarchinitiative.org/pages/disorders/Sick_Sinus_Syndrome_2,_Autosomal_Dominant.html#pathophysiology-hcn4-loss-of-function-variant","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ASick_Sinus_Syndrome_2_Autosomal_Dominant:pathophysiology:Impaired%20Ventricular%20Trabecular%20Compaction","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Ventricular Trabecular Compaction","description":"HCN4 is expressed during cardiac development, and in several independent pedigrees the same segregating HCN4 allele produces both bradycardia and left ventricular noncompaction — a myocardium with a persistently trabeculated, poorly compacted layer and deep intertrabecular recesses. This developmental arm is what distinguishes the HCN4 form of familial sick sinus syndrome from the sodium-channel forms, in which no structural abnormality is found. It is curated here as a parallel branch of the same genetic lesion rather than as maladaptive remodeling secondary to the arrhythmia: the noncompaction is present from childhood and does not follow a preceding phase of cardiomyocyte injury and neurohormonal activation. Some pedigrees additionally show dilation of the ascending aorta.","url":"https://dismech.monarchinitiative.org/pages/disorders/Sick_Sinus_Syndrome_2,_Autosomal_Dominant.html#pathophysiology-impaired-ventricular-trabecular-compaction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ASick_Sinus_Syndrome_2_Autosomal_Dominant:pathophysiology:Loss%20of%20cAMP-Dependent%20Rate%20Modulation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Loss of cAMP-Dependent Rate Modulation","description":"Beta-adrenergic stimulation raises intracellular cAMP, which binds the cyclic-nucleotide-binding domain of HCN4 and shifts activation to more positive voltages, accelerating diastolic depolarization; vagal tone does the reverse. Truncating HCN4 alleles such as 573X delete this domain entirely, so the residual current is insensitive to cAMP. This is the proposed mechanistic basis of chronotropic incompetence in SSS2 — a failure of rate adaptation that is separable from the resting bradycardia. The corresponding mouse model shows that cAMP sensitivity of I_f sets basal and maximal heart rate while relative rate regulation during exercise is partially preserved by other mechanisms.","url":"https://dismech.monarchinitiative.org/pages/disorders/Sick_Sinus_Syndrome_2,_Autosomal_Dominant.html#pathophysiology-loss-of-camp-dependent-rate-modulation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ASick_Sinus_Syndrome_2_Autosomal_Dominant:pathophysiology:Reduced%20Funny%20Current%20and%20Slowed%20Diastolic%20Depolarization","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced Funny Current and Slowed Diastolic Depolarization","description":"The funny current I_f is the hyperpolarization-activated inward cation current that drives the early phase of spontaneous diastolic depolarization in sinoatrial node pacemaker cells. Mutant HCN4 channels activate at more negative voltages than wild-type channels, so at the diastolic potentials actually reached by a pacemaker cell less inward current flows. The diastolic depolarization slope falls, the interval to threshold lengthens, and the intrinsic firing rate of the node drops. The biophysical change has been described as mimicking mild vagal stimulation — a permanent, genetically imposed version of a physiological brake.","url":"https://dismech.monarchinitiative.org/pages/disorders/Sick_Sinus_Syndrome_2,_Autosomal_Dominant.html#pathophysiology-reduced-funny-current-and-slowed-diastolic-depolarization","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Sick_Sinus_Syndrome_2_Autosomal_Dominant.yaml:Patient-derived hiPSC lines carrying a heterozygous and a homozygous HCN4 variant (UKMi009-A, UKMi011-A)","source_id":"model:kb/disorders/Sick_Sinus_Syndrome_2_Autosomal_Dominant.yaml:Patient-derived hiPSC lines carrying a heterozygous and a homozygous HCN4 variant (UKMi009-A, 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cAMP.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":2},{"id":"causal:disorder%3ASick_Sinus_Syndrome_2_Autosomal_Dominant:0:0","source_id":"node:disorder%3ASick_Sinus_Syndrome_2_Autosomal_Dominant:pathophysiology:HCN4%20Loss-of-Function%20Variant","target_id":"node:disorder%3ASick_Sinus_Syndrome_2_Autosomal_Dominant:pathophysiology:Reduced%20Funny%20Current%20and%20Slowed%20Diastolic%20Depolarization","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Reduced channel availability, a hyperpolarizing shift of the activation curve, or dominant-negative suppression of wild-type subunits lowers the inward diastolic current carried by I_f.","intermediate_mechanisms":[],"hypothesis_groups":["sinoatrial_automaticity_failure_model"],"evidence_count":1}]}}],"mechanism_names":["HCN4 Loss-of-Function Variant"],"relationships":["Perturbs"],"fidelities":["Unknown"],"biological_scales":["Molecular"],"system_context_sources":["Linked mechanism anatomy","Linked mechanism cell type","Linked mechanism biological scale"],"modeled_system_labels":["sinoatrial node","cardiac pacemaker cell of sinoatrial 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SND in-vitro disease models in a gene-dose dependent manner.","explanation":"The authors state the intended use of the lines as patient-derived sinus node dysfunction disease models, which is the basis for listing them here."},{"reference":"PMID:40414080","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40414080","reference_title":"Generation of human induced pluripotent stem cell (hiPSC) lines (UKMi009-A and UKMi011-A) harboring a homozygous and heterozygous HCN4 variant from a family with inherited sinus node dysfunction (SND).","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Here, we generated two hiPSC lines from a consanguineous family with SND where the HCN4 variant was either present in heterozygous or homozygous state.","explanation":"Establishes that the lines carry the patient HCN4 variant in a gene-dose series, which is the perturbation this link records."},{"reference":"PMID:40414080","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40414080","reference_title":"Generation of human induced pluripotent stem cell (hiPSC) lines (UKMi009-A and UKMi011-A) harboring a homozygous and heterozygous HCN4 variant from a family with inherited sinus node dysfunction (SND).","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Both cell lines exhibited normal karyotype, cell morphology, hiPSC marker expression, and differentiation into all three germ layers, confirmed by immunofluorescence staining.","explanation":"The reported characterisation stops at pluripotency, which is why the fidelity of this link is recorded as UNKNOWN rather than asserted."}],"evidence_text":["Generated hiPSCs enable further cardiomyocyte cell differentiation to provide unique patient-derived SND in-vitro disease models in a gene-dose dependent manner.","Here, we generated two hiPSC lines from a consanguineous family with SND where the HCN4 variant was either present in heterozygous or homozygous state.","Both cell lines exhibited normal karyotype, cell morphology, hiPSC marker expression, and differentiation into all three germ layers, confirmed by immunofluorescence staining.","The authors state the intended use of the lines as patient-derived sinus node dysfunction disease models, which is the basis for listing them here.","Establishes that the lines carry the patient HCN4 variant in a gene-dose series, which is the perturbation this link records.","The reported characterisation stops at pluripotency, which is why the fidelity of this link is recorded as UNKNOWN rather than asserted."],"evidence_status":"Evidence recorded","metadata_completeness":80,"metadata_present":["Model category","Organism","Anatomy","Cell type","Cell source","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Culture system"],"dataset_context":"Available in same 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Those are consistent with the two pathophysiology nodes this entry curates downstream of the calcium lesion, but they are not curated as separate readouts because the entry does not model transcriptional programmes as nodes.","context_id":"disorder:Darier_Disease","context_kind":"Disorder","disease_name":"Darier Disease","disease_synonyms":[],"disease_term":{"id":"MONDO:0007417","label":"Darier disease","display_label":"Darier disease","url":"http://purl.obolibrary.org/obo/MONDO_0007417"},"experimental_model_type":"ORGANOID","experimental_model_type_label":"Organoid","namo_type":"namo:Organoid","declared_namo_class_name":null,"namo_class_name":"Organoid","namo_class_label":"Organoid","namo_description":"A 3D cell culture system that self-organizes to recapitulate key structural and functional aspects of an organ or tissue","namo_docs_url":"https://monarch-initiative.github.io/namo/elements/Organoid/","namo_ontology_url":"https://w3id.org/monarch-initiative/namo/Organoid","namo_mapping_basis":"Safe mapping from DisMech category","namo_class_in_schema":true,"namo_schema_status":"Defined in NAMO schema used for this build","modality":"Cellular system","organism":{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},"organism_label":"Homo sapiens","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[{"id":"UBERON:0001003","label":"skin epidermis","display_label":"epidermis","url":"http://purl.obolibrary.org/obo/UBERON_0001003"}],"linked_anatomy_labels":["skin epidermis"],"anatomy":[{"id":"UBERON:0001003","label":"skin epidermis","display_label":"epidermis","url":"http://purl.obolibrary.org/obo/UBERON_0001003"}],"anatomy_labels":["skin epidermis"],"tissue_label":null,"model_cell_types":[{"id":"CL:0000312","label":"keratinocyte","display_label":"keratinocyte","url":"http://purl.obolibrary.org/obo/CL_0000312"}],"model_cell_type_labels":["keratinocyte"],"linked_cell_types":[{"id":"CL:0000312","label":"keratinocyte","display_label":"keratinocyte","url":"http://purl.obolibrary.org/obo/CL_0000312"}],"linked_cell_type_labels":["keratinocyte"],"cell_types":[{"id":"CL:0000312","label":"keratinocyte","display_label":"keratinocyte","url":"http://purl.obolibrary.org/obo/CL_0000312"}],"cell_type_labels":["keratinocyte"],"conditions":[],"cell_source":"Keratinocytes from patients with Darier disease.","source_category":"Patient-derived","culture_system":null,"publication":"PMID:41466489","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41466489","mechanisms":[{"target":"Suprabasal Acantholysis","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Darier_Disease.html#pathophysiology-suprabasal-acantholysis","relationship":"RECAPITULATES","relationship_label":"Recapitulates","fidelity":"MODERATE","fidelity_label":"Moderate","description":"The organoid reproduces the acantholytic lesion together with the desmosomal dysfunction and desmosomal protein mislocalisation that underlie it, which is the mechanism this node asserts.","limitations":"An in vitro epidermal system with no dermis, adnexal structures, immune compartment or vasculature, so it cannot model the seborrheic distribution, the secondary infection that drives clinical flares, or any of the extracutaneous disease. 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mislocalisation of desmosomal proteins.","Establishes the model system, its human patient-derived origin, and its purpose.","Supports treating this organoid as informative for Darier disease mechanism, which is the claim the link itself makes.","Reports the measured phenotype of the organoid, naming acantholysis and desmosomal protein mislocalisation."],"evidence_status":"Evidence recorded","metadata_completeness":90,"metadata_present":["Model category","NAMO class","Organism","Anatomy","Cell type","Cell source","Modeled mechanism","Publication","Evidence"],"metadata_missing":["Culture system"],"dataset_context":"None recorded in same 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ICF2-iPSC model is highly relevant to explore the role of ZBTB24 in DNA methylation homeostasis and provides a tool to investigate the early molecular events linking ZBTB24 deficiency to the ICF2 clinical phenotype.","explanation":"The paper directly frames the iPSC model as informative for early ZBTB24-to-phenotype mechanisms."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Immunodeficiency_Centromeric_Instability_Facial_Anomalies_Syndrome","model_node_id":"model:kb/disorders/Immunodeficiency_Centromeric_Instability_Facial_Anomalies_Syndrome.yaml:Patient-derived ICF2 induced pluripotent stem 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However, proplatelet formation was reduced by about 50% with respect to controls.","explanation":"Quantifies the human proplatelet formation deficit against normal differentiation."}],"evidence_text":["These results suggest that a defect of platelet formation contributes to macrothrombocytopenia associated to the Bolzano mutation, and indicate a key role for GPIb alpha in proplatelet formation.","Megakaryocyte differentiation from both cord blood (one patient) and peripheral blood (five patients) was comparable to controls. 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Proplatelet morphology in culture remains a surrogate for platelet release in vivo.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[{"id":"CL:0000556","label":"megakaryocyte","display_label":"megakaryocyte","url":"http://purl.obolibrary.org/obo/CL_0000556"}],"biological_processes":[{"id":"GO:0030220","label":"platelet formation","display_label":"platelet formation","url":"http://purl.obolibrary.org/obo/GO_0030220"},{"id":"GO:0030036","label":"actin cytoskeleton organization","display_label":"actin cytoskeleton organization","url":"http://purl.obolibrary.org/obo/GO_0030036"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Megakaryocyte maturation and proplatelet tip size","description":null,"target":"Abnormal Proplatelet Formation by Megakaryocytes","direction":"ALTERED","interpretation":"Normal maturation with abnormally large proplatelet tips is the pattern that excludes a maturation arrest as the cause of the low platelet count.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:29090484","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/29090484","reference_title":"Mutations of the integrin αIIb/β3 intracytoplasmic salt bridge cause macrothrombocytopenia and enlarged platelet α-granules.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"Analysis of the maturation and development of megakaryocytes reveal no defect in their early maturation but abnormal proplatelet formation was observed with increased size of the tips.","explanation":"The two findings together, which is what makes this a terminal-step defect."}],"notes":null}],"evidence":[{"reference":"PMID:29090484","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/29090484","reference_title":"Mutations of the integrin αIIb/β3 intracytoplasmic salt bridge cause macrothrombocytopenia and enlarged platelet α-granules.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"Analysis of the maturation and development of megakaryocytes reveal no defect in their early maturation but abnormal proplatelet formation was observed with increased size of the tips.","explanation":"The two findings together, which is what makes this a terminal-step defect."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Platelet-type_Bleeding_Disorder_16","model_node_id":"model:kb/disorders/Platelet-type_Bleeding_Disorder_16.yaml:Patient-derived megakaryocyte cultures from ITGA2B R995W carriers","focus_node_id":"node:disorder%3APlatelet-type_Bleeding_Disorder_16:pathophysiology:Abnormal%20Proplatelet%20Formation%20by%20Megakaryocytes","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Platelet-type_Bleeding_Disorder_16.html#pathograph","nodes":[{"id":"model:kb/disorders/Platelet-type_Bleeding_Disorder_16.yaml:Patient-derived megakaryocyte cultures from ITGA2B R995W carriers","kind":"experimental_model","kind_label":"NAM model","label":"Patient-derived megakaryocyte cultures from ITGA2B R995W carriers","description":"Megakaryocyte maturation and proplatelet formation studied in cultures from patients themselves, in three families of which two carry ITGA2B R995W. 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What fails is the terminal step. Proplatelets extend with fewer branches and abnormally large tips, and transduced murine megakaryocytes additionally form asymmetric barbell proplatelets, so each megakaryocyte yields fewer and larger platelets. This is the quantitative arm of the disorder, which the primary_hemostatic_plug_failure module deliberately does not model, so no node here conforms to it.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Platelet-type_Bleeding_Disorder_16.html#pathophysiology-abnormal-proplatelet-formation-by-megakaryocytes","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APlatelet-type_Bleeding_Disorder_16:phenotype:Abnormal%20Platelet%20Alpha-Granules","kind":"phenotype","kind_label":"Phenotype","label":"Abnormal Platelet Alpha-Granules","description":"Enlarged alpha-granules, some giant and showing signs of fusion, on electron microscopy of large round platelets. It was described in families carrying salt-bridge variants including ITGA2B R995W, and the authors left open whether it characterises every variant that disturbs the alphaIIb Arg995 to beta3 Asp723 bridge.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Platelet-type_Bleeding_Disorder_16.html#phenotype-abnormal-platelet-alpha-granules","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APlatelet-type_Bleeding_Disorder_16:pathophysiology:Persistent%20alphaIIbbeta3%20Outside-In%20Signalling","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Persistent alphaIIbbeta3 Outside-In Signalling","description":"The constitutively active receptor signals continuously through the integrin-mediated pathway in megakaryocytes and platelets: focal adhesion kinase is spontaneously phosphorylated, and RhoA activity falls, which is the arm that couples the receptor to the cytoskeleton. In transfected non-haematopoietic cells the same signal produces membrane ruffling and abnormal cytoplasmic protrusions resembling the extensions a megakaryocyte makes when it forms proplatelets.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Platelet-type_Bleeding_Disorder_16.html#pathophysiology-persistent-alphaiibbeta3-outside-in-signalling","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APlatelet-type_Bleeding_Disorder_16:pathophysiology:Reduced%20Output%20of%20Enlarged%20Circulating%20Platelets","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced Output of Enlarged Circulating Platelets","description":"The haematological result: a moderately reduced platelet count with a raised mean platelet volume and a wide platelet size distribution, often with giant forms on the film. Counts in reported families run from the twenties to the low normal range and the immature platelet fraction is raised, which is consistent with a production defect rather than with peripheral destruction. Plasma thrombopoietin is normal, and in one patient the count rose transiently after an influenza infection, both arguing against a profound global failure of thrombopoiesis.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Platelet-type_Bleeding_Disorder_16.html#pathophysiology-reduced-output-of-enlarged-circulating-platelets","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Platelet-type_Bleeding_Disorder_16.yaml:Patient-derived megakaryocyte cultures from ITGA2B R995W carriers","source_id":"model:kb/disorders/Platelet-type_Bleeding_Disorder_16.yaml:Patient-derived megakaryocyte cultures from ITGA2B R995W 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platelets.","intermediate_mechanisms":[],"hypothesis_groups":["constitutive_aiibb3_activation"],"evidence_count":0},{"id":"causal:disorder%3APlatelet-type_Bleeding_Disorder_16:3:0","source_id":"node:disorder%3APlatelet-type_Bleeding_Disorder_16:pathophysiology:Persistent%20alphaIIbbeta3%20Outside-In%20Signalling","target_id":"node:disorder%3APlatelet-type_Bleeding_Disorder_16:pathophysiology:Abnormal%20Proplatelet%20Formation%20by%20Megakaryocytes","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[3].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"The same cytoskeletal signal misdirects the terminal step of platelet production.","intermediate_mechanisms":[],"hypothesis_groups":["constitutive_aiibb3_activation"],"evidence_count":1}]}}],"mechanism_names":["Abnormal Proplatelet Formation by 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and single-cell transcriptomics showed genotype-specific differences between PKD1 and PKD2 organoids, so a PKD1-derived result should not be assumed to hold for PKD2.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[{"id":"CL:0002518","label":"kidney epithelial cell","display_label":"kidney epithelial cell","url":"http://purl.obolibrary.org/obo/CL_0002518"}],"biological_processes":[{"id":"GO:0006874","label":"intracellular calcium ion homeostasis","display_label":"intracellular calcium ion homeostasis","url":"http://purl.obolibrary.org/obo/GO_0006874"}],"pathways":[],"genes":[{"id":"hgnc:9009","label":"PKD2","display_label":"PKD2","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/9009"}],"chemicals":[],"readouts":[],"evidence":[{"reference":"PMID:41946363","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41946363","reference_title":"Patient-derived kidney organoids recapitulate ADPKD and facilitate the identification of Rho pathway inhibitors as candidate therapeutics.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Patient-derived MAROs faithfully reproduced hallmark cystogenic features, including elongated primary cilia, polarity disruption, and elevated Rho GTPase/planar cell polarity (PCP) signaling.","explanation":"Establishes that the organoids reproduce the ciliary and polarity phenotype this node describes."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Polycystic_Kidney_Disease_2","model_node_id":"model:kb/disorders/Polycystic_Kidney_Disease_2.yaml:Patient-derived multi-lineage adult renal organoids","focus_node_id":"node:disorder%3APolycystic_Kidney_Disease_2:pathophysiology:Polycystin-2%20loss%20at%20the%20renal%20primary%20cilium","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Polycystic_Kidney_Disease_2.html#pathograph","nodes":[{"id":"model:kb/disorders/Polycystic_Kidney_Disease_2.yaml:Patient-derived multi-lineage adult renal organoids","kind":"experimental_model","kind_label":"NAM model","label":"Patient-derived multi-lineage adult renal organoids","description":"Expandable organoids grown from ADPKD surgical specimens, including PKD2-mutant donors. 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This is why PKD2 and PKD1 produce the same disease.","url":"https://dismech.monarchinitiative.org/pages/disorders/Polycystic_Kidney_Disease_2.html#pathophysiology-polycystin-2-loss-at-the-renal-primary-cilium","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APolycystic_Kidney_Disease_2:pathophysiology:Cilium-dependent%20cAMP%20elevation%20in%20tubular%20epithelium","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Cilium-dependent cAMP elevation in tubular epithelium","description":"Reduced intracellular calcium disinhibits adenylate cyclase, and vasopressin V2 receptor signalling in the distal nephron and collecting duct amplifies the effect. 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Activity.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We analyzed the transcriptomic response to 1,25D in fibroblasts bearing a severe homozygous hereditary vitamin D resistant rickets-related p.Arg30* VDR mutation (MUT) and in control fibroblasts (CO).","explanation":"Establishes the disease genotype, human primary-cell system, and matched comparator."},{"reference":"PMID:30959822","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30959822","reference_title":"Transcriptomic Response to 1,25-Dihydroxyvitamin D in Human Fibroblasts with or without a Functional Vitamin D Receptor (VDR): Novel Target Genes and Insights into VDR Basal Transcriptional Activity.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Roughly 4.5% of the transcriptome was regulated by 1,25D in CO fibroblasts, while MUT cells without a functional VDR were insensitive to 1,25D.","explanation":"Directly measures the impaired transcriptional response represented by the target node."}],"evidence_text":["We analyzed the transcriptomic response to 1,25D in fibroblasts bearing a severe homozygous hereditary vitamin D resistant rickets-related p.Arg30* VDR mutation (MUT) and in control fibroblasts (CO).","Roughly 4.5% of the transcriptome was regulated by 1,25D in CO fibroblasts, while MUT cells without a functional VDR were insensitive to 1,25D.","Establishes the disease genotype, human primary-cell system, and matched comparator.","Directly measures the impaired transcriptional response represented by the target node."],"evidence_status":"Evidence recorded","metadata_completeness":80,"metadata_present":["Model category","Organism","Cell type","Cell source","Culture system","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Anatomy"],"dataset_context":"Available in same 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A later study used patient-derived hiPSCs for mutation-selective editing.","context_id":"disorder:Autosomal_Dominant_Nonsyndromic_Hearing_Loss_41","context_kind":"Disorder","disease_name":"Autosomal Dominant Nonsyndromic Hearing Loss 41","disease_synonyms":["DFNA41","deafness, autosomal dominant 41","P2RX2 autosomal dominant nonsyndromic deafness","autosomal dominant nonsyndromic deafness caused by mutation in P2RX2","autosomal dominant nonsyndromic deafness type 41","deafness, autosomal dominant type 41","autosomal dominant deafness 41","autosomal dominant nonsyndromic deafness 41"],"disease_term":{"id":"MONDO:0011994","label":"autosomal dominant nonsyndromic hearing loss 41","display_label":"autosomal dominant nonsyndromic hearing loss 41","url":"http://purl.obolibrary.org/obo/MONDO_0011994"},"experimental_model_type":"IPSC_DERIVED_MODEL","experimental_model_type_label":"iPSC-derived model","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},"organism_label":"Homo sapiens","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":"Non-integrative hiPSCs reprogrammed from urine-derived epithelial cells of three members of a large Chinese kindred heterozygous for P2RX2 c.178G>T (p.Val60Leu).","source_category":"iPSC-derived","culture_system":null,"publication":"PMID:30819013","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/30819013","mechanisms":[{"target":"Variant-Specific P2X2 Channel Dysfunction","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_41.html#pathophysiology-variant-specific-p2x2-channel-dysfunction","relationship":"PERTURBS","relationship_label":"Perturbs","fidelity":"UNKNOWN","fidelity_label":"Unknown","description":"Establishes the p.Val60Leu allele at two dosages in a human genetic background: the patients' own heterozygous state, and an engineered homozygote as a control for gene function.","limitations":"Undifferentiated hiPSCs and an engineered homozygous allele-dosage control do not establish cochlear physiology or a human homozygous disease phenotype.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[],"biological_processes":[],"pathways":[],"genes":[{"id":"hgnc:15459","label":"P2RX2","display_label":"P2RX2","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/15459"}],"chemicals":[],"readouts":[],"evidence":[{"reference":"PMID:30819013","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30819013","reference_title":"Efficient introduction of an isogenic homozygous mutation to induced pluripotent stem cells from a hereditary hearing loss family using CRISPR/Cas9 and single-stranded donor oligonucleotides.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"we used CRISPR/Cas9 and single-stranded donor oligonucleotides to genetically establish homozygous P2RX2 c.178G>T hiPSCs (designated P2RX2-/-) from heterozygous patient-specific hiPSCs as a control to further study the pathological gene function.","explanation":"The editing step that makes this a dosage series for the node rather than a single patient line."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Autosomal_Dominant_Nonsyndromic_Hearing_Loss_41","model_node_id":"model:kb/disorders/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_41.yaml:Patient-derived P2RX2 p.Val60Leu hiPSC lines and their CRISPR homozygous isogenic control","focus_node_id":"node:disorder%3AAutosomal_Dominant_Nonsyndromic_Hearing_Loss_41:pathophysiology:Variant-Specific%20P2X2%20Channel%20Dysfunction","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_41.html#pathograph","nodes":[{"id":"model:kb/disorders/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_41.yaml:Patient-derived P2RX2 p.Val60Leu hiPSC lines and their CRISPR homozygous isogenic control","kind":"experimental_model","kind_label":"NAM model","label":"Patient-derived P2RX2 p.Val60Leu hiPSC lines and their CRISPR homozygous isogenic control","description":"Patient-derived heterozygous p.Val60Leu hiPSCs were generated from urine epithelial cells, and CRISPR/ssODN editing introduced the same variant into the remaining allele to create a homozygous dosage model. 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Functional abnormalities of the uncertain p.Asp201Tyr/p.Asp273Tyr variant do not independently prove human disease causality.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_41.html#pathophysiology-variant-specific-p2x2-channel-dysfunction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3AAutosomal_Dominant_Nonsyndromic_Hearing_Loss_41:pathophysiology:Inner%20Hair%20Cell%20and%20Ribbon%20Synapse%20Disorganisation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Inner Hair Cell and Ribbon Synapse Disorganisation","description":"Heterozygous p.Val61Leu mice show shortened inner hair cells and abnormal perinuclear positioning of ribbon synapses. 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Their molecular connection to altered P2X2 gating remains uncertain.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_41.html#pathophysiology-inner-hair-cell-and-ribbon-synapse-disorganisation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3AAutosomal_Dominant_Nonsyndromic_Hearing_Loss_41:pathophysiology:Loss%20of%20Purinergic%20Adaptation%20to%20Elevated%20Sound%20Levels","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Loss of Purinergic Adaptation to Elevated Sound Levels","description":"P2rx2-null mice lack the purinergic component of adaptation to sustained sound. 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Extrapolation to heterozygous human missense disease therefore requires allele-specific testing.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_41.html#pathophysiology-loss-of-purinergic-adaptation-to-elevated-sound-levels","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"}],"edges":[{"id":"model-link:0:model:kb/disorders/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_41.yaml:Patient-derived P2RX2 p.Val60Leu hiPSC lines and their CRISPR homozygous isogenic control","source_id":"model:kb/disorders/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_41.yaml:Patient-derived P2RX2 p.Val60Leu hiPSC lines and their CRISPR homozygous isogenic 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one of the two showed none."}],"notes":null}],"evidence":[{"reference":"PMID:26189817","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/26189817","reference_title":"TRMT5 Mutations Cause a Defect in Post-transcriptional Modification of Mitochondrial tRNA Associated with Multiple Respiratory-Chain Deficiencies.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The transduction had no noticeable effect on the G37 modification status of mt-tRNALeu(CUN) in the control-cell line (C2-T, Figure 5A).","explanation":"The specificity control - transduction changes nothing in control cells - which is what licenses reading the patient-cell change as a rescue."},{"reference":"PMID:26189817","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/26189817","reference_title":"TRMT5 Mutations Cause a Defect in Post-transcriptional Modification of Mitochondrial tRNA Associated with Multiple Respiratory-Chain Deficiencies.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"in transduced 73901 fibroblasts, the expression of wild-type TRMT5 was found to reverse the hypomodification effect observed in fibroblasts from the affected individuals, resulting in m1G37 amounts matching those of the control individual","explanation":"Reports the rescue measurement behind this readout."},{"reference":"PMID:26189817","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/26189817","reference_title":"TRMT5 Mutations Cause a Defect in Post-transcriptional Modification of Mitochondrial tRNA Associated with Multiple Respiratory-Chain Deficiencies.","supports":"REFUTE","evidence_source":"IN_VITRO","snippet":"The latter is also supported by a modestly lowered respiration rate in the 65205 fibroblast (Figure S6), but no detectable changes in oxygen consumption in the 73901 fibroblast.","explanation":"Refutes the proposition that patient fibroblasts reliably show a bioenergetic defect - one of the two showed none."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Combined_Oxidative_Phosphorylation_Defect_Type_26","model_node_id":"model:kb/disorders/Combined_Oxidative_Phosphorylation_Defect_Type_26.yaml:Patient-derived primary fibroblasts with wild-type TRMT5 rescue","focus_node_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Defect_Type_26:pathophysiology:m1G37%20Hypomodification%20of%20Mitochondrial%20tRNA","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Oxidative_Phosphorylation_Defect_Type_26.html#pathograph","nodes":[{"id":"model:kb/disorders/Combined_Oxidative_Phosphorylation_Defect_Type_26.yaml:Patient-derived primary fibroblasts with wild-type TRMT5 rescue","kind":"experimental_model","kind_label":"NAM model","label":"Patient-derived primary fibroblasts with wild-type TRMT5 rescue","description":"Fibroblasts from both founding individuals, with lentiviral re-expression of wild-type TRMT5 cDNA as the rescue arm. 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Steady-state mt-tRNA-Leu(CUN) levels are similar in control and patient fibroblasts, so the downstream defect is a translation-fidelity or efficiency problem rather than a loss of the tRNA pool.","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Oxidative_Phosphorylation_Defect_Type_26.html#pathophysiology-m1g37-hypomodification-of-mitochondrial-trna","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Defect_Type_26:pathophysiology:Impaired%20Mitochondrial%20Translation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Mitochondrial Translation","description":"m1G37 sits immediately 3' of the anticodon and maintains reading-frame fidelity and translational efficiency; losing it degrades synthesis of the thirteen mtDNA-encoded respiratory-chain subunits. 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one of the two showed none."}],"evidence_text":["The transduction had no noticeable effect on the G37 modification status of mt-tRNALeu(CUN) in the control-cell line (C2-T, Figure 5A).","in transduced 73901 fibroblasts, the expression of wild-type TRMT5 was found to reverse the hypomodification effect observed in fibroblasts from the affected individuals, resulting in m1G37 amounts matching those of the control individual","The latter is also supported by a modestly lowered respiration rate in the 65205 fibroblast (Figure S6), but no detectable changes in oxygen consumption in the 73901 fibroblast.","The specificity control - transduction changes nothing in control cells - which is what licenses reading the patient-cell change as a rescue.","Reports the rescue measurement behind this readout.","Refutes the proposition that patient fibroblasts reliably show a bioenergetic defect - one of the two showed none."],"evidence_status":"Evidence recorded","metadata_completeness":40,"metadata_present":["Model category","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Organism","Anatomy","Cell type","Cell source","Culture system"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Combined_Oxidative_Phosphorylation_Defect_Type_26.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Combined_Oxidative_Phosphorylation_Defect_Type_26.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Oxidative_Phosphorylation_Defect_Type_26.html#experimental-model-patient-derived-primary-fibroblasts-with-wild-type-trmt5-rescue","source_anchor":"experimental-model-patient-derived-primary-fibroblasts-with-wild-type-trmt5-rescue"},{"id":"model:kb/disorders/Autosomal_Recessive_Hypercholesterolemia.yaml:Patient-derived primary lymphocytes","name":"Patient-derived primary lymphocytes","description":"Mevastatin-treated lymphocytes exposed to recombinant PCSK9 with or without alirocumab. 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this nonhepatic assay informs the shared defect but does not measure hepatic clearance or prove clinical antibody efficacy.","biological_scale":"CELLULAR","anatomy":[{"id":"UBERON:0002107","label":"liver","display_label":"liver","url":"http://purl.obolibrary.org/obo/UBERON_0002107"}],"cell_types":[{"id":"CL:0000182","label":"hepatocyte","display_label":"hepatocyte","url":"http://purl.obolibrary.org/obo/CL_0000182"}],"biological_processes":[{"id":"GO:0072583","label":"clathrin-dependent endocytosis","display_label":"clathrin-dependent endocytosis","url":"http://purl.obolibrary.org/obo/GO_0072583"},{"id":"GO:0006898","label":"receptor-mediated endocytosis","display_label":"receptor-mediated endocytosis","url":"http://purl.obolibrary.org/obo/GO_0006898"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Fluorescent LDL uptake","description":"Reduced cellular LDL uptake reproduces an ARH endocytic defect in lymphocytes.","target":"Impaired Clathrin-Mediated Endocytosis of the Hepatocyte LDL Receptor","direction":"DECREASED","interpretation":null,"biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:27079874","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/27079874","reference_title":"Proprotein Convertase Subtilisin Kexin Type 9 Inhibition for Autosomal Recessive Hypercholesterolemia-Brief Report.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Fluorescent LDL cellular uptake, also measured by flow cytometry, was reduced in ARH lymphocytes compared with control lymphocytes.","explanation":"Patient-cell uptake measurement, distinct from plasma LDL-C response."}],"notes":null}],"evidence":[{"reference":"PMID:27079874","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/27079874","reference_title":"Proprotein Convertase Subtilisin Kexin Type 9 Inhibition for Autosomal Recessive Hypercholesterolemia-Brief Report.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Fluorescent LDL cellular uptake, also measured by flow cytometry, was reduced in ARH lymphocytes compared with control lymphocytes.","explanation":"Patient-cell uptake measurement, distinct from plasma LDL-C response."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Autosomal_Recessive_Hypercholesterolemia","model_node_id":"model:kb/disorders/Autosomal_Recessive_Hypercholesterolemia.yaml:Patient-derived primary lymphocytes","focus_node_id":"node:disorder%3AAutosomal_Recessive_Hypercholesterolemia:pathophysiology:Impaired%20Clathrin-Mediated%20Endocytosis%20of%20the%20Hepatocyte%20LDL%20Receptor","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Recessive_Hypercholesterolemia.html#pathograph","nodes":[{"id":"model:kb/disorders/Autosomal_Recessive_Hypercholesterolemia.yaml:Patient-derived primary lymphocytes","kind":"experimental_model","kind_label":"NAM model","label":"Patient-derived primary lymphocytes","description":"Mevastatin-treated lymphocytes exposed to recombinant PCSK9 with or without alirocumab. 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The defect is cargo and cell dependent rather than a global failure of clathrin endocytosis. Patient lymphocytes also show reduced LDL uptake, while cultured skin fibroblasts can retain normal LDL-receptor function. In mouse hepatocytes, LDLR-dependent VLDL-remnant uptake persists despite failure to internalize LDL. Fibroblast DAB2-dependent maintenance of receptor protein complicates a simple redundant-adaptor explanation.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Recessive_Hypercholesterolemia.html#pathophysiology-impaired-clathrin-mediated-endocytosis-of-the-hepatocyte-ldl-receptor","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAutosomal_Recessive_Hypercholesterolemia:pathophysiology:Impaired%20Hepatic%20Clearance%20of%20Plasma%20LDL","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Hepatic Clearance of Plasma LDL","description":"Plasma LDL-apoB removal is reduced. In one ARH patient, a stable-isotope study estimated LDL-apoB fractional catabolism of 0.109/day versus 0.450 ± 0.122/day in seven controls. Atorvastatin increased this patient's rate to 0.464/day. This demonstrates substantial reversibility in that individual and does not establish a universal value for all LDLRAP1 genotypes.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Recessive_Hypercholesterolemia.html#pathophysiology-impaired-hepatic-clearance-of-plasma-ldl","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAutosomal_Recessive_Hypercholesterolemia:pathophysiology:Loss%20of%20ARH%20Adaptor%20Bridging%20of%20the%20LDL%20Receptor%20to%20Clathrin","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Loss of ARH Adaptor Bridging of the LDL Receptor to Clathrin","description":"The ARH phosphotyrosine-binding domain interacts with the LDLR cytoplasmic tail, while clathrin- and AP-2-binding regions connect it to coated-pit machinery. Domain-rescue experiments require the PTB domain plus either clathrin or AP-2 binding for effective clustering and LDL uptake. LDLRAP1 disease primarily affects this adaptor function rather than the LDLR coding sequence; receptor abundance and residual activity nevertheless depend on cell and allele context.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Recessive_Hypercholesterolemia.html#pathophysiology-loss-of-arh-adaptor-bridging-of-the-ldl-receptor-to-clathrin","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Autosomal_Recessive_Hypercholesterolemia.yaml:Patient-derived primary lymphocytes","source_id":"model:kb/disorders/Autosomal_Recessive_Hypercholesterolemia.yaml:Patient-derived primary lymphocytes","target_id":"node:disorder%3AAutosomal_Recessive_Hypercholesterolemia:pathophysiology:Impaired%20Clathrin-Mediated%20Endocytosis%20of%20the%20Hepatocyte%20LDL%20Receptor","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"Reduced cellular LDL uptake reproduces an ARH endocytic defect in lymphocytes.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AAutosomal_Recessive_Hypercholesterolemia:2:0","source_id":"node:disorder%3AAutosomal_Recessive_Hypercholesterolemia:pathophysiology:Impaired%20Clathrin-Mediated%20Endocytosis%20of%20the%20Hepatocyte%20LDL%20Receptor","target_id":"node:disorder%3AAutosomal_Recessive_Hypercholesterolemia:pathophysiology:Impaired%20Hepatic%20Clearance%20of%20Plasma%20LDL","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[0]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"Reduced hepatic LDL uptake contributes to slow plasma LDL-apoB removal; human kinetic data establish the clearance defect without measuring every cellular intermediary.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3AAutosomal_Recessive_Hypercholesterolemia:1:0","source_id":"node:disorder%3AAutosomal_Recessive_Hypercholesterolemia:pathophysiology:Loss%20of%20ARH%20Adaptor%20Bridging%20of%20the%20LDL%20Receptor%20to%20Clathrin","target_id":"node:disorder%3AAutosomal_Recessive_Hypercholesterolemia:pathophysiology:Impaired%20Clathrin-Mediated%20Endocytosis%20of%20the%20Hepatocyte%20LDL%20Receptor","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Impaired adaptor coupling reduces receptor clustering and internalization of LDL cargo in the tested hepatocyte systems.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1}]}}],"mechanism_names":["Impaired Clathrin-Mediated Endocytosis of the Hepatocyte LDL Receptor"],"relationships":["Recapitulates"],"fidelities":["Moderate"],"biological_scales":["Cellular"],"system_context_sources":["Linked mechanism anatomy","Linked mechanism cell type","Linked mechanism biological scale"],"modeled_system_labels":["liver","hepatocyte","Cellular"],"biological_process_terms":[{"id":"GO:0072583","label":"clathrin-dependent endocytosis","display_label":"clathrin-dependent endocytosis","url":"http://purl.obolibrary.org/obo/GO_0072583"},{"id":"GO:0006898","label":"receptor-mediated endocytosis","display_label":"receptor-mediated endocytosis","url":"http://purl.obolibrary.org/obo/GO_0006898"}],"biological_processes":["clathrin-dependent endocytosis","receptor-mediated endocytosis"],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":["Fluorescent LDL uptake"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:27079874","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/27079874","reference_title":"Proprotein Convertase Subtilisin Kexin Type 9 Inhibition for Autosomal Recessive Hypercholesterolemia-Brief Report.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Fluorescent LDL cellular uptake, also measured by flow cytometry, was reduced in ARH lymphocytes compared with control lymphocytes.","explanation":"Patient-cell uptake measurement, distinct from plasma LDL-C response."}],"evidence_text":["Fluorescent LDL cellular uptake, also measured by flow cytometry, was reduced in ARH lymphocytes compared with control lymphocytes.","Patient-cell uptake measurement, distinct from plasma LDL-C response."],"evidence_status":"Evidence recorded","metadata_completeness":70,"metadata_present":["Model category","Anatomy","Cell type","Cell source","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Organism","Culture system"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Autosomal_Recessive_Hypercholesterolemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autosomal_Recessive_Hypercholesterolemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Recessive_Hypercholesterolemia.html#experimental-model-patient-derived-primary-lymphocytes","source_anchor":"experimental-model-patient-derived-primary-lymphocytes"},{"id":"model:kb/disorders/Autosomal_Dominant_Optic_Atrophy.yaml:Patient-derived primary skin fibroblasts with heterozygous OPA1 mutations","name":"Patient-derived primary skin fibroblasts with heterozygous OPA1 mutations","description":"Four primary skin fibroblast lines carrying different heterozygous OPA1 mutations — nonsense and missense, in the GTPase and the C-terminal coiled-coil domains — analysed in parallel and quantitatively, which was the point of the study: earlier fibroblast reports had been mutually inconsistent. The panel shows defective fusion on pharmacological challenge, abnormal fragmentation under glycolysis shortage or oxidative stress, reduced complex IV activity, and distorted cristae, with a physical OPA1-oxidative-phosphorylation interaction on reciprocal immunoprecipitation. It is the human in vitro counterweight to the study of isolated patient mitochondria that found electron transport unaltered.","notes":"The paper's closing sentence is the caveat that should travel with every use of it: \"Identifying whether the observed alterations are also present in ganglion retinal cells, and which of them underlies their degeneration process remains however an essential goal for therapeutic strategy.\"","context_id":"disorder:Autosomal_Dominant_Optic_Atrophy","context_kind":"Disorder","disease_name":"Autosomal Dominant Optic Atrophy","disease_synonyms":["Kjer optic atrophy","Kjer-type optic atrophy","optic atrophy type 1","OPA1","autosomal dominant optic atrophy, Kjer type","juvenile optic atrophy"],"disease_term":{"id":"MONDO:0008134","label":"autosomal dominant optic atrophy, classic form","display_label":"autosomal dominant optic atrophy, classic form","url":"http://purl.obolibrary.org/obo/MONDO_0008134"},"experimental_model_type":"PRIMARY_CELL_CULTURE","experimental_model_type_label":"Primary-cell culture","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},"organism_label":"Homo sapiens","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[{"id":"CL:0000740","label":"retinal ganglion cell","display_label":"Retinal ganglion cell","url":"http://purl.obolibrary.org/obo/CL_0000740"}],"linked_cell_type_labels":["retinal ganglion cell"],"cell_types":[{"id":"CL:0000740","label":"retinal ganglion cell","display_label":"Retinal ganglion cell","url":"http://purl.obolibrary.org/obo/CL_0000740"}],"cell_type_labels":["retinal ganglion cell"],"conditions":[],"cell_source":null,"source_category":"Primary / biopsy-derived","culture_system":null,"publication":"PMID:22800932","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/22800932","mechanisms":[{"target":"Cristae Disorganization","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Dominant_Optic_Atrophy.html#pathophysiology-cristae-disorganization","relationship":"RECAPITULATES","relationship_label":"Recapitulates","fidelity":"MODERATE","fidelity_label":"Moderate","description":"Altered cristae structure is present in patient fibroblasts carrying heterozygous OPA1 mutations.","limitations":"Skin fibroblasts are not the affected cell type, and the paper says so itself: whether these alterations are present in retinal ganglion cells, and which of them drives degeneration, is left as an open goal. The fusion defect also required pharmacological challenge to become apparent, so the unstressed phenotype is mild.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0042407","label":"cristae formation","display_label":"Cristae formation","url":"http://purl.obolibrary.org/obo/GO_0042407"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[],"evidence":[{"reference":"PMID:22800932","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/22800932","reference_title":"Defective mitochondrial fusion, altered respiratory function, and distorted cristae structure in skin fibroblasts with heterozygous OPA1 mutations.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Altered cristae structure coexisted with normal response to pro-apoptotic stimuli and expression of Bax or Bcl2 proteins.","explanation":"Documents the cristae abnormality in patient cells, and in the same sentence the absence of an apoptotic-response abnormality — relevant because it does not reproduce the lowered apoptotic threshold that cultured OPA1-knockdown cells show."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Autosomal_Dominant_Optic_Atrophy","model_node_id":"model:kb/disorders/Autosomal_Dominant_Optic_Atrophy.yaml:Patient-derived primary skin fibroblasts with heterozygous OPA1 mutations","focus_node_id":"node:disorder%3AAutosomal_Dominant_Optic_Atrophy:pathophysiology:Cristae%20Disorganization","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Dominant_Optic_Atrophy.html#pathograph","nodes":[{"id":"model:kb/disorders/Autosomal_Dominant_Optic_Atrophy.yaml:Patient-derived primary skin fibroblasts with heterozygous OPA1 mutations","kind":"experimental_model","kind_label":"NAM model","label":"Patient-derived primary skin fibroblasts with heterozygous OPA1 mutations","description":"Four primary skin fibroblast lines carrying different heterozygous OPA1 mutations — nonsense and missense, in the GTPase and the C-terminal coiled-coil domains — analysed in parallel and quantitatively, which was the point of the study: earlier fibroblast reports had been mutually inconsistent. The panel shows defective fusion on pharmacological challenge, abnormal fragmentation under glycolysis shortage or oxidative stress, reduced complex IV activity, and distorted cristae, with a physical OPA1-oxidative-phosphorylation interaction on reciprocal immunoprecipitation. It is the human in vitro counterweight to the study of isolated patient mitochondria that found electron transport unaltered.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Dominant_Optic_Atrophy.html#experimental-model-patient-derived-primary-skin-fibroblasts-with-heterozygous-opa1-mutations","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAutosomal_Dominant_Optic_Atrophy:pathophysiology:Cristae%20Disorganization","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Cristae Disorganization","description":"OPA1 is a major organizer of the mitochondrial inner membrane; cristae integrity depends on it. Reducing OPA1 drastically disorganizes the cristae. Critically, this function is genetically and molecularly distinct from fusion — OPA1 keeps cristae junctions tight through oligomers of its soluble intermembrane-space and integral inner-membrane forms, and does so independently of its profusion activity. Curating it as its own node rather than folding it into the fusion node is the point: a cristae defect alone is sufficient to compromise respiratory-complex organization and cytochrome c retention.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Dominant_Optic_Atrophy.html#pathophysiology-cristae-disorganization","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAutosomal_Dominant_Optic_Atrophy:pathophysiology:Loss%20of%20Cytochrome%20c%20Sequestration","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Loss of Cytochrome c Sequestration","description":"OPA1 oligomers keep cristae junctions tight during apoptosis and so retain the intracristal cytochrome c pool. This is a protective function exerted independently of fusion: OPA1 does not interfere with activation of BAX and BAK, but the proapoptotic BH3 protein BID, which widens cristae junctions, disrupts OPA1 oligomers. Losing it lowers the threshold for cytochrome c release, and in cultured cells reducing OPA1 commits the cell to apoptosis with no other stimulus applied.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Dominant_Optic_Atrophy.html#pathophysiology-loss-of-cytochrome-c-sequestration","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAutosomal_Dominant_Optic_Atrophy:pathophysiology:OPA1%20Haploinsufficiency","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"OPA1 Haploinsufficiency","description":"A heterozygous OPA1 null allele — premature termination codon, frameshift, splice-site defect, or large-scale rearrangement — halves the dose of functional OPA1 protein. This, rather than a poisoned oligomer, is the predominant mechanism of the classic non-syndromic form: the mutation spectrum is weighted towards truncating alleles, and a mouse carrying the recurrent human c.2708_2711delTTAG allele shows a greater than 40% reduction in Opa1 mRNA, which the authors read as supporting haploinsufficiency. Missense alleles in the GTPase domain, which act dominant-negatively, are instead enriched in the syndromic DOA plus form curated separately.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Dominant_Optic_Atrophy.html#pathophysiology-opa1-haploinsufficiency","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAutosomal_Dominant_Optic_Atrophy:pathophysiology:Oxidative%20Phosphorylation%20Deficiency","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Oxidative Phosphorylation Deficiency","description":"The four upstream arms converge here. 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punch biopsy also yielded abnormally truncated GP130 isoforms on western blot","explanation":"Measures the cellular biochemical consequence."}],"evidence_text":["Determination of mannosyltransferase activities of early steps of lipid-linked oligosaccharide biosynthesis in fibroblasts indicated that the patient was deficient in elongating Man3GlcNAc2-PP-dolichol.","Analysis of dolichol-linked oligosaccharides in patient-derived fibroblasts revealed an accumulation of Man3GlcNAc2-PP-dolichol and Man4GlcNAc2-PP-dolichol.","Fibroblasts from the skin punch biopsy also yielded abnormally truncated GP130 isoforms on western blot","Supports treating patient fibroblasts as informative for this node.","The measurement itself.","Measures the cellular biochemical consequence."],"evidence_status":"Evidence recorded","metadata_completeness":60,"metadata_present":["Model category","Organism","Cell type","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Anatomy","Cell 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That two unrelated index patients with different nonsense alleles looked alike is what made this a recognizable syndrome rather than a collection of malformations.","url":"https://dismech.monarchinitiative.org/pages/disorders/Sandestig-Stefanova_Syndrome.html#pathophysiology-impaired-craniofacial-and-distal-limb-morphogenesis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ASandestig-Stefanova_Syndrome:pathophysiology:Impaired%20Lens%20and%20Anterior%20Eye%20Development","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Lens and Anterior Eye Development","description":"Congenital bilateral cataract with microphthalmia. Cataract is one of the two or three features that make the syndrome recognizable, and it was present in four of the six individuals in the defining series. No lens tissue from an affected individual has been examined, so the node asserts the developmental failure without specifying its cellular route - in particular, no crystallin aggregation has been demonstrated here.","url":"https://dismech.monarchinitiative.org/pages/disorders/Sandestig-Stefanova_Syndrome.html#pathophysiology-impaired-lens-and-anterior-eye-development","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ASandestig-Stefanova_Syndrome:pathophysiology:Impaired%20Neuronal%20Dendrite%20Development","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Neuronal Dendrite Development","description":"Removing NUP188 in Drosophila produces aberrant dendrite tiling alongside motor deficits and seizure susceptibility. 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The review that prompted this section proposed a skeletal-muscle-specific Aco2 knockout mouse (PMID:41331265) and an A252T knock-in mouse (PMID:38007539). Both were fetched and read: the first is titled \"Critical role of mitochondrial aconitase in skeletal muscle maturation\" and studies unloading-induced muscle atrophy; the second is titled \"ACO2 deficiency increases vulnerability to Parkinson's disease\" and studies dopaminergic neurodegeneration. Neither mentions infantile cerebellar-retinal degeneration at all. They share the gene, not the disease, and curating either as a model of this disorder would be the gene-mediated Named Entity Confusion the curation rules warn about.","context_id":"disorder:Infantile_Cerebellar-Retinal_Degeneration","context_kind":"Disorder","disease_name":"Infantile Cerebellar-Retinal Degeneration","disease_synonyms":["ICRD","infantile cerebellar retinal degeneration","ACO2 deficiency","mitochondrial aconitase deficiency","cerebellar-retinal degeneration, infantile"],"disease_term":{"id":"MONDO:0013802","label":"infantile cerebellar-retinal degeneration","display_label":"infantile cerebellar-retinal degeneration","url":"http://purl.obolibrary.org/obo/MONDO_0013802"},"experimental_model_type":"PRIMARY_CELL_CULTURE","experimental_model_type_label":"Primary-cell culture","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":null,"source_category":"Primary / biopsy-derived","culture_system":null,"publication":"PMID:26992325","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/26992325","mechanisms":[{"target":"Krebs Cycle Flux Block","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Infantile_Cerebellar-Retinal_Degeneration.html#pathophysiology-krebs-cycle-flux-block","relationship":"MEASURES","relationship_label":"Measures","fidelity":"MODERATE","fidelity_label":"Moderate","description":"Reports the cellular consequences of the aconitase block in patient tissue: deficient respiration, mitochondrial DNA depletion, and altered expression of TCA and electron-transport components.","limitations":"Fibroblasts are not an affected tissue in this disorder, which targets cerebellum and retina, so the findings establish that the variants are pathogenic and that consequences propagate beyond aconitase itself, not that these are the events that kill neurons and photoreceptors. A single patient's cells.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0006099","label":"tricarboxylic acid cycle","display_label":"tricarboxylic acid cycle","url":"http://purl.obolibrary.org/obo/GO_0006099"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[],"evidence":[{"reference":"PMID:26992325","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/26992325","reference_title":"Functional cellular analyses reveal energy metabolism defect and mitochondrial DNA depletion in a case of mitochondrial aconitase deficiency.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Our findings demonstrate the pathogenicity of two VUS in ACO2, provide novel mechanistic insights to TCA disturbances in ACO2 deficiency, and implicate mitochondrial DNA depletion in the pathogenesis of this recently described disorder.","explanation":"The authors' own statement of what the model establishes, which is pathogenicity plus a downstream mechanism rather than a disease model."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Infantile_Cerebellar-Retinal_Degeneration","model_node_id":"model:kb/disorders/Infantile_Cerebellar-Retinal_Degeneration.yaml:Patient-derived skin fibroblasts with compound heterozygous ACO2 variants","focus_node_id":"node:disorder%3AInfantile_Cerebellar-Retinal_Degeneration:pathophysiology:Krebs%20Cycle%20Flux%20Block","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Infantile_Cerebellar-Retinal_Degeneration.html#pathograph","nodes":[{"id":"model:kb/disorders/Infantile_Cerebellar-Retinal_Degeneration.yaml:Patient-derived skin fibroblasts with compound heterozygous ACO2 variants","kind":"experimental_model","kind_label":"NAM model","label":"Patient-derived skin fibroblasts with compound heterozygous ACO2 variants","description":"Fibroblasts from a patient with compound heterozygous ACO2 missense variants of uncertain significance, used to establish pathogenicity functionally and to characterise the downstream metabolic consequences.","url":"https://dismech.monarchinitiative.org/pages/disorders/Infantile_Cerebellar-Retinal_Degeneration.html#experimental-model-patient-derived-skin-fibroblasts-with-compound-heterozygous-aco2-variants","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AInfantile_Cerebellar-Retinal_Degeneration:pathophysiology:Krebs%20Cycle%20Flux%20Block","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Krebs Cycle Flux Block","description":"An isolated interruption of the tricarboxylic acid cycle. 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Vision is normal in the newborn period and then deteriorates, so the process is degenerative rather than a failure of development.","url":"https://dismech.monarchinitiative.org/pages/disorders/Infantile_Cerebellar-Retinal_Degeneration.html#pathophysiology-progressive-neuronal-and-photoreceptor-degeneration","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AInfantile_Cerebellar-Retinal_Degeneration:pathophysiology:Reduced%20Mitochondrial%20Aconitase%20Activity","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced Mitochondrial Aconitase Activity","description":"Loss of the enzyme that converts citrate to isocitrate via cis-aconitate. This was measured directly in patient lymphoblasts and found severely reduced, which is what makes the enzymatic deficit an observation rather than an inference from the genotype.","url":"https://dismech.monarchinitiative.org/pages/disorders/Infantile_Cerebellar-Retinal_Degeneration.html#pathophysiology-reduced-mitochondrial-aconitase-activity","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Infantile_Cerebellar-Retinal_Degeneration.yaml:Patient-derived skin fibroblasts with compound heterozygous ACO2 variants","source_id":"model:kb/disorders/Infantile_Cerebellar-Retinal_Degeneration.yaml:Patient-derived skin fibroblasts with compound heterozygous ACO2 variants","target_id":"node:disorder%3AInfantile_Cerebellar-Retinal_Degeneration:pathophysiology:Krebs%20Cycle%20Flux%20Block","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Measures","directed":false,"relationship":"MEASURES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"Reports the cellular consequences of the aconitase block in patient tissue: deficient respiration, mitochondrial DNA depletion, and altered expression of TCA and electron-transport components.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AInfantile_Cerebellar-Retinal_Degeneration:2:0","source_id":"node:disorder%3AInfantile_Cerebellar-Retinal_Degeneration:pathophysiology:Krebs%20Cycle%20Flux%20Block","target_id":"node:disorder%3AInfantile_Cerebellar-Retinal_Degeneration:pathophysiology:Progressive%20Neuronal%20and%20Photoreceptor%20Degeneration","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[0]","label":"Causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":null,"causal_link_type_label":null,"description":"The proposed route from the metabolic block to tissue loss. The selective vulnerability of cerebellum, optic nerve and retina is not explained by anything curated here; see the knowledge gap.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3AInfantile_Cerebellar-Retinal_Degeneration:1:0","source_id":"node:disorder%3AInfantile_Cerebellar-Retinal_Degeneration:pathophysiology:Reduced%20Mitochondrial%20Aconitase%20Activity","target_id":"node:disorder%3AInfantile_Cerebellar-Retinal_Degeneration:pathophysiology:Krebs%20Cycle%20Flux%20Block","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[0]","label":"Causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":null,"causal_link_type_label":null,"description":"The citrate-to-isocitrate step is the committed point the enzyme catalyses, so its loss interrupts flux through the 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Voluntary cough improved clearance and represents a partly compensating mechanism; regional deposition and cough complicate interpretation of whole-lung tracer measurements.","url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Ciliary_Dyskinesia.html#pathophysiology-impaired-mucociliary-clearance","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APrimary_Ciliary_Dyskinesia:phenotype:Abnormal%20Sputum","kind":"phenotype","kind_label":"Phenotype","label":"Abnormal Sputum","description":null,"url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Ciliary_Dyskinesia.html#phenotype-abnormal-sputum","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APrimary_Ciliary_Dyskinesia:phenotype:Atelectasis","kind":"phenotype","kind_label":"Phenotype","label":"Atelectasis","description":null,"url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Ciliary_Dyskinesia.html#phenotype-atelectasis","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APrimary_Ciliary_Dyskinesia:pathophysiology:Central-Apparatus%20Transport%20Dysfunction","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Central-Apparatus Transport Dysfunction","description":"Loss of C1d projection components can impair collective ciliary transport despite apparently normal beat frequency, waveform, routine TEM and nasal nitric oxide. The nine-person characterization included CFAP46, CFAP54, CFAP74 and CFAP221 variants, with transport experiments on available patient cultures. The physiological transport endpoint therefore complements routine single-cilium observations. Clinical gene-validity grades differ and should not be inferred from inclusion in one functional study.","url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Ciliary_Dyskinesia.html#pathophysiology-central-apparatus-transport-dysfunction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3APrimary_Ciliary_Dyskinesia:pathophysiology:Chronic%20Airway%20Infection%20and%20Neutrophilic%20Inflammation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Chronic Airway Infection and Neutrophilic Inflammation","description":"Retained secretions favor persistent airway infection, neutrophil recruitment and protease/oxidative injury. 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Antibiotic-responsive sputum elastase and ex vivo macrophage responses demonstrate inflammatory complexity without replacing the neutrophil-dominant clinical phenotype.","url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Ciliary_Dyskinesia.html#pathophysiology-chronic-airway-infection-and-neutrophilic-inflammation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APrimary_Ciliary_Dyskinesia:phenotype:Chronic%20Cough","kind":"phenotype","kind_label":"Phenotype","label":"Chronic Cough","description":null,"url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Ciliary_Dyskinesia.html#phenotype-chronic-cough","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APrimary_Ciliary_Dyskinesia:phenotype:Chronic%20Otitis%20Media","kind":"phenotype","kind_label":"Phenotype","label":"Chronic Otitis Media","description":null,"url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Ciliary_Dyskinesia.html#phenotype-chronic-otitis-media","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APrimary_Ciliary_Dyskinesia:phenotype:Chronic%20Rhinitis","kind":"phenotype","kind_label":"Phenotype","label":"Chronic Rhinitis","description":null,"url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Ciliary_Dyskinesia.html#phenotype-chronic-rhinitis","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APrimary_Ciliary_Dyskinesia:phenotype:Chronic%20Rhinosinusitis","kind":"phenotype","kind_label":"Phenotype","label":"Chronic Rhinosinusitis","description":null,"url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Ciliary_Dyskinesia.html#phenotype-chronic-rhinosinusitis","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APrimary_Ciliary_Dyskinesia:pathophysiology:Ciliary%20Disorientation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Ciliary Disorientation","description":"GAS2L2 deficiency disrupts orientation of airway motile cilia despite preserved axonemal ultrastructure. 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Conditional Gas2l2 deletion impairs clearance in mice, supporting a transport consequence without establishing that every normal-TEM PCD genotype shares this mechanism.","url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Ciliary_Dyskinesia.html#pathophysiology-ciliary-disorientation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APrimary_Ciliary_Dyskinesia:pathophysiology:Ciliary%20Dysfunction","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Ciliary Dysfunction","description":"Defects in dynein motors, their cytoplasmic assembly or docking, and axonemal regulatory structures impair coordinated ciliary movement. 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This beat-dysfunction route is distinct from reduced multiciliogenesis and transport failure despite apparently normal routine beat measurements.","url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Ciliary_Dyskinesia.html#pathophysiology-ciliary-dysfunction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APrimary_Ciliary_Dyskinesia:phenotype:Conductive%20Hearing%20Impairment","kind":"phenotype","kind_label":"Phenotype","label":"Conductive Hearing Impairment","description":null,"url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Ciliary_Dyskinesia.html#phenotype-conductive-hearing-impairment","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APrimary_Ciliary_Dyskinesia:phenotype:Hearing%20Loss","kind":"phenotype","kind_label":"Phenotype","label":"Hearing Loss","description":null,"url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Ciliary_Dyskinesia.html#phenotype-hearing-loss","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APrimary_Ciliary_Dyskinesia:phenotype:Nasal%20Congestion","kind":"phenotype","kind_label":"Phenotype","label":"Nasal Congestion","description":null,"url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Ciliary_Dyskinesia.html#phenotype-nasal-congestion","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APrimary_Ciliary_Dyskinesia:phenotype:Nasal%20Polyposis","kind":"phenotype","kind_label":"Phenotype","label":"Nasal Polyposis","description":null,"url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Ciliary_Dyskinesia.html#phenotype-nasal-polyposis","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APrimary_Ciliary_Dyskinesia:phenotype:Neonatal%20Respiratory%20Distress","kind":"phenotype","kind_label":"Phenotype","label":"Neonatal Respiratory Distress","description":null,"url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Ciliary_Dyskinesia.html#phenotype-neonatal-respiratory-distress","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APrimary_Ciliary_Dyskinesia:phenotype:Otitis%20Media","kind":"phenotype","kind_label":"Phenotype","label":"Otitis Media","description":null,"url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Ciliary_Dyskinesia.html#phenotype-otitis-media","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APrimary_Ciliary_Dyskinesia:pathophysiology:Periciliary%20Barrier%20Dysfunction","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Periciliary Barrier Dysfunction","description":"CCDC39/CCDC40-deficient cell cultures have altered epithelial composition and a defective periciliary barrier, providing a potential additional impediment to airway surface transport. 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Nodal monocilia are generally spared by CCNO/MCIDAS defects; that negative prediction does not extend to every ciliogenesis gene.","url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Ciliary_Dyskinesia.html#pathophysiology-reduced-multiciliogenesis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APrimary_Ciliary_Dyskinesia:phenotype:Sinusitis","kind":"phenotype","kind_label":"Phenotype","label":"Sinusitis","description":null,"url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Ciliary_Dyskinesia.html#phenotype-sinusitis","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APrimary_Ciliary_Dyskinesia:phenotype:Wheezing","kind":"phenotype","kind_label":"Phenotype","label":"Wheezing","description":null,"url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Ciliary_Dyskinesia.html#phenotype-wheezing","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:1:model:kb/disorders/Primary_Ciliary_Dyskinesia.yaml:Patient-specific hiPSC-derived airway epithelium model","source_id":"model:kb/disorders/Primary_Ciliary_Dyskinesia.yaml:Patient-specific hiPSC-derived airway epithelium model","target_id":"node:disorder%3APrimary_Ciliary_Dyskinesia:pathophysiology:Impaired%20Mucociliary%20Clearance","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[1]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"Patient-specific hiPSC airway epithelia reproduce impaired culture-surface transport.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3APrimary_Ciliary_Dyskinesia:3:0","source_id":"node:disorder%3APrimary_Ciliary_Dyskinesia:pathophysiology:Central-Apparatus%20Transport%20Dysfunction","target_id":"node:disorder%3APrimary_Ciliary_Dyskinesia:pathophysiology:Impaired%20Mucociliary%20Clearance","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[3].downstream[0]","label":"Indirectly causes (known intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_KNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Known Intermediates","description":"This ciliary defect impairs effective respiratory surface transport.","intermediate_mechanisms":[],"hypothesis_groups":["canonical_motile_cilia_beat_failure"],"evidence_count":1},{"id":"causal:disorder%3APrimary_Ciliary_Dyskinesia:2:0","source_id":"node:disorder%3APrimary_Ciliary_Dyskinesia:pathophysiology:Ciliary%20Disorientation","target_id":"node:disorder%3APrimary_Ciliary_Dyskinesia:pathophysiology:Impaired%20Mucociliary%20Clearance","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[0]","label":"Indirectly causes (known intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_KNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Known Intermediates","description":"Loss of common ciliary orientation can reduce effective directional transport; 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motility and ultrastructure","Mucociliary transport"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[{"statement":"Patient-specific hiPSC-derived airway epithelium reproduces molecular, ultrastructural, and functional ciliary defects, including impaired mucociliary transport","evidence":[{"reference":"PMID:37296588","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/37296588","reference_title":"Primary Ciliary Dyskinesia Patient-Specific hiPSC-Derived Airway Epithelium in Air-Liquid Interface Culture Recapitulates Disease Specific Phenotypes In Vitro.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Applying transmission electron microscopy, immunofluorescence staining, ciliary beat frequency, and mucociliary transport measurements, we could demonstrate that ciliated respiratory epithelia cells derived from two PCD patient-specific hiPSC lines carrying mutations in DNAH5 and NME5, respectively, recapitulate the respective diseased phenotype on a molecular, structural and functional level.","explanation":"Shows that hiPSC-derived airway epithelium reproduces the molecular and functional consequences of PCD mutations, including impaired transport."}]}],"findings_text":["Patient-specific hiPSC-derived airway epithelium reproduces molecular, ultrastructural, and functional ciliary defects, including impaired mucociliary transport"],"evidence":[{"reference":"PMID:37296588","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/37296588","reference_title":"Primary Ciliary Dyskinesia Patient-Specific hiPSC-Derived Airway Epithelium in Air-Liquid Interface Culture Recapitulates Disease Specific Phenotypes In Vitro.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Here, we developed an in vitro model for PCD based on human induced pluripotent stem cell (hiPSC)-derived airway epithelium in Air-Liquid-Interface cultures.","explanation":"Establishes hiPSC-derived airway epithelium as a PCD-specific in vitro model."},{"reference":"PMID:37296588","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/37296588","reference_title":"Primary Ciliary Dyskinesia Patient-Specific hiPSC-Derived Airway Epithelium in Air-Liquid Interface Culture Recapitulates Disease Specific Phenotypes In Vitro.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Motile cilia dysfunction results in diminished mucociliary clearance (MCC) of pathogens in the respiratory tract and chronic airway inflammation and infections successively causing progressive lung damage.","explanation":"Connects the model's mucociliary transport readouts to the central airway pathophysiology of PCD."},{"reference":"PMID:37296588","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/37296588","reference_title":"Primary Ciliary Dyskinesia Patient-Specific hiPSC-Derived Airway Epithelium in Air-Liquid Interface Culture Recapitulates Disease Specific Phenotypes In Vitro.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Applying transmission electron microscopy, immunofluorescence staining, ciliary beat frequency, and mucociliary transport measurements, we could demonstrate that ciliated respiratory epithelia cells derived from two PCD patient-specific hiPSC lines carrying mutations in DNAH5 and NME5, respectively, recapitulate the respective diseased phenotype on a molecular, structural and functional level.","explanation":"Shows that hiPSC-derived airway epithelium reproduces the molecular and functional consequences of PCD mutations, including impaired transport."}],"evidence_text":["Here, we developed an in vitro model for PCD based on human induced pluripotent stem cell (hiPSC)-derived airway epithelium in Air-Liquid-Interface cultures.","Motile cilia dysfunction results in diminished mucociliary clearance (MCC) of pathogens in the respiratory tract and chronic airway inflammation and infections successively causing progressive lung damage.","Applying transmission electron microscopy, immunofluorescence staining, ciliary beat frequency, and mucociliary transport measurements, we could demonstrate that ciliated respiratory epithelia cells derived from two PCD patient-specific hiPSC lines carrying mutations in DNAH5 and NME5, respectively, recapitulate the respective diseased phenotype on a molecular, structural and functional level.","Establishes hiPSC-derived airway epithelium as a PCD-specific in vitro model.","Connects the model's mucociliary transport readouts to the central airway pathophysiology of PCD.","Shows that hiPSC-derived airway epithelium reproduces the molecular and functional consequences of PCD mutations, including impaired transport."],"evidence_status":"Evidence recorded","metadata_completeness":100,"metadata_present":["Model category","NAMO class","Organism","Anatomy","Cell type","Cell source","Culture system","Modeled mechanism","Publication","Evidence"],"metadata_missing":[],"dataset_context":"Available in same entry","context_dataset_ids":["dataset:geo:gse254100","dataset:geo:gse272189"],"candidate_dataset_ids":[],"source_path":"kb/disorders/Primary_Ciliary_Dyskinesia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Primary_Ciliary_Dyskinesia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Ciliary_Dyskinesia.html#experimental-model-patient-specific-hipsc-derived-airway-epithelium-model","source_anchor":"experimental-model-patient-specific-hipsc-derived-airway-epithelium-model"},{"id":"model:kb/disorders/Dilated_Cardiomyopathy.yaml:Patient-specific TNNT2 R173W iPSC-derived cardiomyocytes (Clinical Trials in a Dish)","name":"Patient-specific TNNT2 R173W iPSC-derived cardiomyocytes (Clinical Trials in a Dish)","description":"Cardiomyocytes differentiated from induced pluripotent stem cells reprogrammed from skin fibroblasts of a three-generation family carrying the autosomal dominant sarcomeric TNNT2 R173W mutation, with mutation-negative relatives from the same family serving as isogenic-adjacent controls. A non-animal New Approach Methodology that puts the patient's own genotype into a dish and supports both disease modelling and pharmacological rescue testing.","notes":"Curated from the NAMeRS 2026 symposium New Approach Methodology tracker (monarch-initiative/dismech#4873), Panel 1 Clinical Trials in a Dish case study. No `namo_type` is recorded. NAMO defines no iPSC-derived model class (checked against its 56 classes) and its CellularSystem parent is abstract, so the choice was among the concrete culture-format siblings, and none of the three describes this system: CellLineModel is scoped to immortalized lines; ThreeDCellCulture fits the embryoid-body differentiation stage but not cells assayed after dissociation; TwoDCellCulture fits the single cardiomyocytes on atomic force microscopy and microelectrode arrays but not the 3D stage that produced them. The system spans two formats and NAMO has no value for the derivation that actually distinguishes it, so the slot is left absent rather than made to pick a half. `experimental_model_type: IPSC_DERIVED_MODEL` carries the distinction instead, and the upstream gap is monarch-initiative/namo#24. An earlier revision of this record used a coined InducedPluripotentStemCellDerivedModel CURIE (written here without its prefix so that prefix censuses over `kb/` do not match this file), which does not exist in NAMO; nothing validates `namo_type`, so it passed every gate. The adrenergic-stress readouts are split by direction because the source sentence reports both a fall in beating rate and contraction and a rise in cells with abnormal sarcomeric alpha-actinin, and `direction` is single-valued. The underlying evidence item was already cited on the Sarcomeric and Cytoskeletal Dysfunction node; this section adds the structured model record, its pathograph links and the rescue and adrenergic-stress readouts.","context_id":"disorder:Dilated_Cardiomyopathy","context_kind":"Disorder","disease_name":"Dilated Cardiomyopathy","disease_synonyms":["DCM","dilated cardiomyopathy","congestive cardiomyopathy","IDC","idiopathic dilated cardiomyopathy"],"disease_term":{"id":"MONDO:0005021","label":"dilated cardiomyopathy","display_label":"dilated cardiomyopathy","url":"http://purl.obolibrary.org/obo/MONDO_0005021"},"experimental_model_type":"IPSC_DERIVED_MODEL","experimental_model_type_label":"iPSC-derived model","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},"organism_label":"Homo sapiens","model_tissue":[{"id":"UBERON:0000948","label":"heart","display_label":"heart","url":"http://purl.obolibrary.org/obo/UBERON_0000948"}],"model_tissue_labels":["heart"],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[{"id":"UBERON:0000948","label":"heart","display_label":"heart","url":"http://purl.obolibrary.org/obo/UBERON_0000948"}],"anatomy_labels":["heart"],"tissue_label":"heart","model_cell_types":[{"id":"CL:0000746","label":"cardiac muscle cell","display_label":"iPSC-derived cardiomyocyte","url":"http://purl.obolibrary.org/obo/CL_0000746"}],"model_cell_type_labels":["cardiac muscle cell"],"linked_cell_types":[{"id":"CL:0000746","label":"cardiac muscle cell","display_label":"cardiomyocyte","url":"http://purl.obolibrary.org/obo/CL_0000746"}],"linked_cell_type_labels":["cardiac muscle cell"],"cell_types":[{"id":"CL:0000746","label":"cardiac muscle cell","display_label":"iPSC-derived cardiomyocyte","url":"http://purl.obolibrary.org/obo/CL_0000746"}],"cell_type_labels":["cardiac muscle cell"],"conditions":["familial dilated cardiomyopathy with the TNNT2 R173W sarcomeric mutation","beta-adrenergic agonist stress with norepinephrine","beta-blocker and SERCA2a rescue"],"cell_source":"Patient-derived: iPSC lines reprogrammed from skin fibroblasts of four TNNT2 R173W carriers and three mutation-negative relatives in one family cohort","source_category":"Patient-derived","culture_system":"Embryoid-body cardiac differentiation followed by dissociated beating clusters and single cardiomyocytes, assayed by immunocytochemistry, transmission electron microscopy, calcium transient imaging, microelectrode arrays and atomic force microscopy","publication":"PMID:22517884","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/22517884","mechanisms":[{"target":"Sarcomeric and Cytoskeletal Dysfunction","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy.html#pathophysiology-sarcomeric-and-cytoskeletal-dysfunction","relationship":"PARTIALLY_RECAPITULATES","relationship_label":"Partially Recapitulates","fidelity":"MODERATE","fidelity_label":"Moderate","description":"Cardiomyocytes carrying the patient's TNNT2 R173W allele reproduce the sarcomeric disorganisation and contractile failure of this node in human cells, and the phenotype is reversed by beta-blockade or SERCA2a overexpression.","limitations":"The authors themselves qualify the model as recapitulating the disease phenotype only to some extent. The cardiomyocytes are developmentally immature, with mitochondria and sarcoplasmic reticulum still immature at the assay stage, and the sarcomeric defect was most pronounced in single cells and at cluster edges rather than in well-coupled tissue. 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SERCA2a overexpression","description":null,"target":"Sarcomeric and Cytoskeletal Dysfunction","direction":"RESTORED","interpretation":"The model supports a rescue arm: both a beta-blocker and SERCA2a overexpression improved cardiomyocyte function, so the phenotype is pharmacologically reversible in vitro rather than a fixed differentiation artefact.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:22517884","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/22517884","reference_title":"Patient-specific induced pluripotent stem cells as a model for familial dilated cardiomyopathy.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Treatment with β-adrenergic blockers or overexpression of sarcoplasmic reticulum Ca(2+) adenosine triphosphatase (Serca2a) improved the function of iPSC-derived cardiomyocytes from DCM patients","explanation":"Reports the rescue measurement, in the improving direction, behind this readout."}],"notes":null}],"evidence":[{"reference":"PMID:22517884","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/22517884","reference_title":"Patient-specific induced pluripotent stem cells as a model for familial dilated cardiomyopathy.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"iPSC-derived cardiomyocytes from DCM patients recapitulate to some extent the morphological and functional phenotypes of DCM","explanation":"Supports treating this model as informative for the node, with the authors' own partial-recapitulation qualifier carried through to the link relationship."},{"reference":"PMID:22517884","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/22517884","reference_title":"Patient-specific induced pluripotent stem cells as a model for familial dilated cardiomyopathy.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"a significant higher percentage of DCM iPSC-CMs (n=391) showed a punctate distribution of sarcomeric α-actinin over one fourth of the total cellular area","explanation":"Quantifies the sarcomeric disorganisation measurement behind this readout against within-family controls."},{"reference":"PMID:22517884","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/22517884","reference_title":"Patient-specific induced pluripotent stem cells as a model for familial dilated cardiomyopathy.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"cardiomyocytes derived from iPSCs from DCM patients exhibited altered regulation of calcium ion (Ca(2+)), decreased contractility, and abnormal distribution of sarcomeric α-actinin","explanation":"Reports the contractility and calcium-handling measurements made in this model."},{"reference":"PMID:22517884","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/22517884","reference_title":"Patient-specific induced pluripotent stem cells as a model for familial dilated cardiomyopathy.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Treatment with β-adrenergic 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The renal cysts and neuronal migration defects of the severe Zellweger phenotype are long established; in the PEX19 patient reported in 2025 the malformations were unilateral renal agenesis, a cardiac septal defect and a patent ductus. No mechanistic account links peroxisome loss to these specific defects, and this node exists to carry the reported associations rather than to assert a pathway.","url":"https://dismech.monarchinitiative.org/pages/disorders/Peroxisome_Biogenesis_Disorder_12A_Zellweger.html#pathophysiology-congenital-structural-malformation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APeroxisome_Biogenesis_Disorder_12A_Zellweger:pathophysiology:Craniofacial%20and%20Skeletal%20Dysmorphogenesis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Craniofacial and Skeletal Dysmorphogenesis","description":"The Zellweger facies and the bone findings. 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Because the claim is about a protein-protein interaction rather than a nucleotide-sugar pool, no amount of oral galactose addresses it - which is the point of curating it as a separate arm.","url":"https://dismech.monarchinitiative.org/pages/disorders/PGM1-congenital_disorder_of_glycosylation.html#pathophysiology-z-disk-destabilization-via-loss-of-pgm1-ldb3-interaction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:1:model:kb/disorders/PGM1-Congenital_Disorder_of_Glycosylation.yaml:PGM1-deficient patient-derived iPSC-cardiomyocytes","source_id":"model:kb/disorders/PGM1-Congenital_Disorder_of_Glycosylation.yaml:PGM1-deficient patient-derived iPSC-cardiomyocytes","target_id":"node:disorder%3APGM1-Congenital_Disorder_of_Glycosylation:pathophysiology:Cardiomyocyte%20Energetic%20and%20Mitochondrial%20Failure","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[1]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"Extends the mitochondrial arm from mouse heart and PGM1-null skeletal muscle cells into human cardiomyocytes.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3APGM1-Congenital_Disorder_of_Glycosylation:10:0","source_id":"node:disorder%3APGM1-Congenital_Disorder_of_Glycosylation:pathophysiology:Cardiomyocyte%20Energetic%20and%20Mitochondrial%20Failure","target_id":"node:disorder%3APGM1-Congenital_Disorder_of_Glycosylation:pathophysiology:Dilated%20Cardiomyopathy%20and%20Progressive%20Heart%20Failure","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[10].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":null,"intermediate_mechanisms":[],"hypothesis_groups":["galactose_resistant_cardiomyopathy"],"evidence_count":0},{"id":"causal:disorder%3APGM1-Congenital_Disorder_of_Glycosylation:2:2","source_id":"node:disorder%3APGM1-Congenital_Disorder_of_Glycosylation:pathophysiology:Impaired%20Glycogen%20Synthesis%20and%20Glycogenolysis","target_id":"node:disorder%3APGM1-Congenital_Disorder_of_Glycosylation:pathophysiology:Cardiomyocyte%20Energetic%20and%20Mitochondrial%20Failure","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[2]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"The same inability to route glycogen-derived carbon into glycolysis compromises cardiomyocyte energy supply. This is arm (a) of the galactose-resistant-cardiomyopathy hypothesis.","intermediate_mechanisms":[],"hypothesis_groups":["galactose_resistant_cardiomyopathy"],"evidence_count":0},{"id":"causal:disorder%3APGM1-Congenital_Disorder_of_Glycosylation:12:0","source_id":"node:disorder%3APGM1-Congenital_Disorder_of_Glycosylation:pathophysiology:Z-Disk%20Destabilization%20via%20Loss%20of%20PGM1-LDB3%20Interaction","target_id":"node:disorder%3APGM1-Congenital_Disorder_of_Glycosylation:pathophysiology:Cardiomyocyte%20Energetic%20and%20Mitochondrial%20Failure","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[12].downstream[0]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"Loss of Z-disk-mitochondrial coupling is the proposed route from sarcomeric destabilization to the energetic failure of the myocyte.","intermediate_mechanisms":[],"hypothesis_groups":["galactose_resistant_cardiomyopathy"],"evidence_count":1}]}}],"mechanism_names":["Z-Disk Destabilization via Loss of PGM1-LDB3 Interaction","Cardiomyocyte Energetic and Mitochondrial Failure"],"relationships":["Recapitulates"],"fidelities":["Moderate"],"biological_scales":["Cellular"],"system_context_sources":["Linked mechanism cell type","Linked mechanism biological scale"],"modeled_system_labels":["cardiac muscle cell","Cellular"],"biological_process_terms":[{"id":"GO:0045214","label":"sarcomere organization","display_label":"sarcomere organization","url":"http://purl.obolibrary.org/obo/GO_0045214"},{"id":"GO:0006754","label":"ATP biosynthetic process","display_label":"ATP biosynthetic process","url":"http://purl.obolibrary.org/obo/GO_0006754"}],"biological_processes":["sarcomere organization","ATP biosynthetic process"],"pathway_terms":[],"pathways":[],"gene_terms":[{"id":"hgnc:8905","label":"PGM1","display_label":"PGM1","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/8905"}],"genes":["PGM1"],"chemical_terms":[],"chemicals":[],"readout_names":["Z-disk component abundance, LDB3 included","Contractile function by multielectrode array","Mitochondrial respiration"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:41723528","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41723528","reference_title":"PGM1 deficiency is linked to sarcomeric and mitochondrial dysfunction in patient-derived iPSC-cardiomyocytes.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Multielectrode array (MEA) recordings, untargeted (glyco)proteomics, and pathway analysis were performed to assess functional and molecular changes.","explanation":"Describes the model's readout platform."},{"reference":"PMID:41723528","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41723528","reference_title":"PGM1 deficiency is linked to sarcomeric and mitochondrial dysfunction in patient-derived iPSC-cardiomyocytes.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Induced pluripotent stem cell-derived cardiomyocytes (iCMs) were generated from PGM1-deficient patient fibroblasts.","explanation":"Establishes that the model is patient-derived and therefore informative for the human cardiac node."},{"reference":"PMID:41723528","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41723528","reference_title":"PGM1 deficiency is linked to sarcomeric and mitochondrial dysfunction in patient-derived iPSC-cardiomyocytes.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Proteomic analyses revealed depletion of Z-disk components, including LDB3.","explanation":"Reports the measurement and its direction."},{"reference":"PMID:41723528","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41723528","reference_title":"PGM1 deficiency is linked to sarcomeric and mitochondrial dysfunction in patient-derived iPSC-cardiomyocytes.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"PGM1-deficient iCMs exhibited reduced beating frequency, impaired contractility, and prolonged contraction kinetics.","explanation":"Reports the contractile measurements directly."},{"reference":"PMID:41723528","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41723528","reference_title":"PGM1 deficiency is linked to sarcomeric and mitochondrial dysfunction in patient-derived iPSC-cardiomyocytes.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Recent evidence of mitochondrial abnormalities in PGM1-deficient human and murine heart","explanation":"Places the model's mitochondrial finding in the context of prior human and mouse cardiac evidence."},{"reference":"PMID:41723528","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41723528","reference_title":"PGM1 deficiency is linked to sarcomeric and mitochondrial dysfunction in patient-derived iPSC-cardiomyocytes.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Functional validation confirmed extensive metabolic rewiring, energy depletion, and severely impaired mitochondrial respiration.","explanation":"Reports the respiration and energy measurements."}],"evidence_text":["Multielectrode array (MEA) recordings, untargeted (glyco)proteomics, and pathway analysis were performed to assess functional and molecular changes.","Induced pluripotent stem cell-derived cardiomyocytes (iCMs) were generated from PGM1-deficient patient fibroblasts.","Proteomic analyses revealed depletion of Z-disk components, including LDB3.","PGM1-deficient iCMs exhibited reduced beating frequency, impaired contractility, and prolonged contraction kinetics.","Recent evidence of mitochondrial abnormalities in PGM1-deficient human and murine heart","Functional validation confirmed extensive metabolic rewiring, energy depletion, and severely impaired mitochondrial respiration.","Describes the model's readout platform.","Establishes that the model is patient-derived and therefore informative for the human cardiac node.","Reports the measurement and its direction.","Reports the contractile measurements directly.","Places the model's mitochondrial finding in the context of prior human and mouse cardiac evidence.","Reports the respiration and energy measurements."],"evidence_status":"Evidence recorded","metadata_completeness":80,"metadata_present":["Model category","Organism","Cell type","Cell source","Culture system","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Anatomy"],"dataset_context":"None recorded in same 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It models the molecular mechanism of the hyperphosphatasia branch, not the neuronal phenotype.","notes":null,"context_id":"disorder:Developmental_And_Epileptic_Encephalopathy_80","context_kind":"Disorder","disease_name":"Developmental And Epileptic Encephalopathy 80","disease_synonyms":["DEE80","EIEE80","early infantile epileptic encephalopathy 80","EIEE-80","glycosylphosphatidylinositol biosynthesis defect 20","GPIBD20","PIGB-related developmental and epileptic encephalopathy"],"disease_term":{"id":"MONDO:0032822","label":"developmental and epileptic encephalopathy, 80","display_label":"developmental and epileptic encephalopathy, 80","url":"http://purl.obolibrary.org/obo/MONDO_0032822"},"experimental_model_type":"CELL_LINE","experimental_model_type_label":"Cell line","namo_type":"namo:CellLineModel","declared_namo_class_name":null,"namo_class_name":"CellLineModel","namo_class_label":"Cell Line Model","namo_description":"A model system based on immortalized cell lines that can be maintained in culture indefinitely. 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it does not model the developmental and epileptic encephalopathy, and the PIGB mutant is an engineered null rather than a patient hypomorphic allele.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[],"biological_processes":[],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Soluble alkaline phosphatase released into culture medium","description":null,"target":"Shedding of GPI-Anchored Alkaline Phosphatase into Serum","direction":"INCREASED","interpretation":"In vitro correlate of the patient hyperphosphatasia: the PIGB-deficient line sheds ALP into the medium instead of retaining it at the surface.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:22228761","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/22228761","reference_title":"Mechanism for release of alkaline phosphatase caused by glycosylphosphatidylinositol deficiency in patients with hyperphosphatasia mental retardation syndrome.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The GPI-anchored protein was secreted substantially into medium from PIGV-, PIGB-, and PIGF-deficient CHO cells, in which incomplete GPI bearing mannose was accumulated.","explanation":"Reports the measured secretion of ALP into the medium from the PIGB-deficient CHO line, the readout that grounds this model's link to the shedding node."}],"notes":null}],"evidence":[{"reference":"PMID:22228761","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/22228761","reference_title":"Mechanism for release of alkaline phosphatase caused by glycosylphosphatidylinositol deficiency in patients with hyperphosphatasia mental retardation syndrome.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"In contrast, ALP was degraded in PIGL-, DPM2-, or PIGX-deficient CHO cells, in which incomplete shorter GPIs that lacked mannose were accumulated.","explanation":"The mannose-lacking CHO mutants degrade rather than secrete ALP, so the secretion seen in the PIGB-deficient line is specific to the mannose-bearing lesion class - establishing this model as informative for the PIGB shedding mechanism specifically."},{"reference":"PMID:22228761","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/22228761","reference_title":"Mechanism for release of alkaline phosphatase caused by glycosylphosphatidylinositol deficiency in patients with hyperphosphatasia mental retardation syndrome.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The GPI-anchored protein was secreted substantially into medium from PIGV-, PIGB-, and PIGF-deficient CHO cells, in which incomplete GPI bearing mannose was accumulated.","explanation":"Reports the measured secretion of ALP into the medium from the PIGB-deficient CHO line, the readout that grounds this model's link to the shedding node."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Developmental_And_Epileptic_Encephalopathy_80","model_node_id":"model:kb/disorders/Developmental_And_Epileptic_Encephalopathy_80.yaml:PIGB-deficient CHO cell mutant","focus_node_id":"node:disorder%3ADevelopmental_And_Epileptic_Encephalopathy_80:pathophysiology:Shedding%20of%20GPI-Anchored%20Alkaline%20Phosphatase%20into%20Serum","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Developmental_And_Epileptic_Encephalopathy_80.html#pathograph","nodes":[{"id":"model:kb/disorders/Developmental_And_Epileptic_Encephalopathy_80.yaml:PIGB-deficient CHO cell mutant","kind":"experimental_model","kind_label":"NAM model","label":"PIGB-deficient CHO cell mutant","description":"The workhorse heterologous system for the ALP-shedding biochemistry of synthesis-stage GPI deficiency. 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This is the molecular mechanism of hyperphosphatasia in mannose-bearing GPI defects, and it contrasts with the mannose-lacking defects (e.g. PIGL), in which ALP is degraded rather than secreted and serum ALP is not elevated.","url":"https://dismech.monarchinitiative.org/pages/disorders/Developmental_And_Epileptic_Encephalopathy_80.html#pathophysiology-shedding-of-gpi-anchored-alkaline-phosphatase-into-serum","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ADevelopmental_And_Epileptic_Encephalopathy_80:phenotype:Elevated%20circulating%20alkaline%20phosphatase%20concentration","kind":"phenotype","kind_label":"Phenotype","label":"Elevated circulating alkaline phosphatase concentration","description":"Elevated serum alkaline phosphatase (hyperphosphatasia) is seen in most tested patients and is characteristic of inherited GPI deficiency; alkaline phosphatase is itself a GPI-anchored ectoenzyme. 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The synthetic interface mutation is not a clinical therapy.","context_id":"disorder:Auriculocondylar_Syndrome","context_kind":"Disorder","disease_name":"Auriculocondylar Syndrome","disease_synonyms":["auriculo-condylar syndrome","question mark ear syndrome","dysgnathia complex"],"disease_term":{"id":"MONDO:0000107","label":"auriculocondylar syndrome","display_label":"auriculocondylar syndrome","url":"http://purl.obolibrary.org/obo/MONDO_0000107"},"experimental_model_type":"CELL_LINE","experimental_model_type_label":"Cell line","namo_type":"namo:CellLineModel","declared_namo_class_name":null,"namo_class_name":"CellLineModel","namo_class_label":"Cell Line Model","namo_description":"A model system based on immortalized cell lines that can be maintained in culture indefinitely. 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Roughly a fifth of isolated cases are de novo, arising during oogenesis in the mother.","url":"https://dismech.monarchinitiative.org/pages/disorders/X-Linked_Nephrogenic_Diabetes_Insipidus.html#pathophysiology-avpr2-loss-of-function-variant","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AX-Linked_Nephrogenic_Diabetes_Insipidus:pathophysiology:Loss%20of%20Vasopressin-Stimulated%20cAMP%20and%20PKA%20Signalling","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Loss of Vasopressin-Stimulated cAMP and PKA Signalling","description":"Vasopressin normally acts on the principal cell through a single linear cascade: V2 receptor occupancy activates the stimulatory G protein Gs, Gs activates adenylyl cyclase, cAMP rises, and cAMP activates protein kinase A. 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LDLRAP1 disease primarily affects this adaptor function rather than the LDLR coding sequence; receptor abundance and residual activity nevertheless depend on cell and allele context.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Recessive_Hypercholesterolemia.html#pathophysiology-loss-of-arh-adaptor-bridging-of-the-ldl-receptor-to-clathrin","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Autosomal_Recessive_Hypercholesterolemia.yaml:Polarized WIF-B hepatocytes","source_id":"model:kb/disorders/Autosomal_Recessive_Hypercholesterolemia.yaml:Polarized WIF-B 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Chronically elevated PTH drives high-turnover bone disease with increased osteoclastic resorption and extends to the cardiovascular system promoting vascular calcifications.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/CKD-Mineral_Bone_Disorder.html#pathophysiology-secondary-hyperparathyroidism","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/CKD-Mineral_Bone_Disorder.yaml:Primary human vascular CPP bioassay model","source_id":"model:kb/disorders/CKD-Mineral_Bone_Disorder.yaml:Primary human vascular CPP bioassay 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The abnormality is mild, matching the mild to moderate clinical cutis laxa rather than the near-absent elastic network seen in some other cutis laxa subtypes.","url":"https://dismech.monarchinitiative.org/pages/disorders/Cutis_Laxa_Autosomal_Recessive_Type_2E.html#pathophysiology-abnormal-dermal-elastic-fiber-architecture","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ACutis_Laxa_Autosomal_Recessive_Type_2E:pathophysiology:Loose%20Anchoring%20of%20the%20Large%20Latent%20Complex%20in%20Fibrillin%20Microfibrils","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Loose Anchoring of the Large Latent Complex in Fibrillin Microfibrils","description":"Truncated LTBP1 still forms fibers, but only rudimentary ones, and the large latent complex it carries is no longer held securely in the microfibril network. The authors' proposal is that latent complexes which fail to be targeted to the matrix are activated inappropriately.","url":"https://dismech.monarchinitiative.org/pages/disorders/Cutis_Laxa_Autosomal_Recessive_Type_2E.html#pathophysiology-loose-anchoring-of-the-large-latent-complex-in-fibrillin-microfibrils","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"}],"edges":[{"id":"model-link:1:model:kb/disorders/Cutis_Laxa_Autosomal_Recessive_Type_2E.yaml:Proband dermal fibroblast cultures (c.4844del and c.1342C>T)","source_id":"model:kb/disorders/Cutis_Laxa_Autosomal_Recessive_Type_2E.yaml:Proband dermal fibroblast cultures (c.4844del and c.1342C>T)","target_id":"node:disorder%3ACutis_Laxa_Autosomal_Recessive_Type_2E:pathophysiology:Failure%20of%20Fibulin-4%20Incorporation%20into%20the%20Elastic%20Fiber%20Scaffold","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[1]","label":"Measures","directed":false,"relationship":"MEASURES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"Immunofluorescent analysis of the matrix fraction at 9 days post-confluency for fibulin-4, LTBP1, LTBP2, fibrillin-1, and collagens I and III.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ACutis_Laxa_Autosomal_Recessive_Type_2E:6:0","source_id":"node:disorder%3ACutis_Laxa_Autosomal_Recessive_Type_2E:pathophysiology:Failure%20of%20Fibulin-4%20Incorporation%20into%20the%20Elastic%20Fiber%20Scaffold","target_id":"node:disorder%3ACutis_Laxa_Autosomal_Recessive_Type_2E:pathophysiology:Abnormal%20Dermal%20Elastic%20Fiber%20Architecture","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[6].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ACutis_Laxa_Autosomal_Recessive_Type_2E:5:1","source_id":"node:disorder%3ACutis_Laxa_Autosomal_Recessive_Type_2E:pathophysiology:Loose%20Anchoring%20of%20the%20Large%20Latent%20Complex%20in%20Fibrillin%20Microfibrils","target_id":"node:disorder%3ACutis_Laxa_Autosomal_Recessive_Type_2E:pathophysiology:Failure%20of%20Fibulin-4%20Incorporation%20into%20the%20Elastic%20Fiber%20Scaffold","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[5].downstream[1]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1}]}}],"mechanism_names":["Excess TGF-beta Activation and Canonical Smad2 Signaling","Failure of Fibulin-4 Incorporation into the Elastic Fiber Scaffold"],"relationships":["Measures"],"fidelities":["Moderate"],"biological_scales":["Cellular","Molecular"],"system_context_sources":["Linked mechanism cell type","Linked mechanism biological scale"],"modeled_system_labels":["skin fibroblast","Cellular","Molecular"],"biological_process_terms":[{"id":"GO:0007179","label":"transforming growth factor beta receptor signaling pathway","display_label":"transforming growth factor beta receptor signaling pathway","url":"http://purl.obolibrary.org/obo/GO_0007179"},{"id":"GO:0060395","label":"SMAD protein signal transduction","display_label":"SMAD protein signal transduction","url":"http://purl.obolibrary.org/obo/GO_0060395"},{"id":"GO:0048251","label":"elastic fiber assembly","display_label":"elastic fiber assembly","url":"http://purl.obolibrary.org/obo/GO_0048251"}],"biological_processes":["transforming growth factor beta receptor signaling pathway","SMAD protein signal transduction","elastic fiber assembly"],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":["Total TGF-beta in conditioned medium"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:33991472","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33991472","reference_title":"Bi-allelic premature truncating variants in LTBP1 cause cutis laxa syndrome.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We used dermal fibroblasts cultured from skin biopsies of F1:IV-2 and F4:II-1 in this study. 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The gain-of-function effect in the latter model requires the calmodulin-binding region, limiting extrapolation to the ANFH2 C-terminal allele.","url":"https://dismech.monarchinitiative.org/pages/disorders/Avascular_Necrosis_of_Femoral_Head,_Primary,_2.html#pathophysiology-increased-osteoclast-bone-resorption","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAvascular_Necrosis_Of_Femoral_Head_Primary_2:pathophysiology:Prolonged%20TRPV4%20Channel%20Activity","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Prolonged TRPV4 Channel Activity","description":"Longer calcium sparklet bursts in proband fibroblasts and mutant-transduced HEK293 cells support impaired channel closure. 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This is the only human cardiomyocyte system in which a PSEN1 variant has been studied, and it finds a sarcoplasmic-reticulum calcium leak that is not blocked by ryanodine-receptor or IP3-receptor inhibition, producing a diastolic calcium buildup near the perinuclear SR and less releasable calcium during systole.\nThe allele is wrong for this entry. PSEN1 delta-exon-9 is a familial Alzheimer disease variant, not the CMD1U Asp333Gly allele, and the patients were ascertained for dementia. So this system does not resolve the tissue mismatch that this entry's central hypothesis rests on - it narrows it, by showing that a PSEN1 variant can disturb cardiomyocyte calcium in human cells, while leaving open whether the CMD1U allele does.","notes":null,"context_id":"disorder:Dilated_Cardiomyopathy_1U","context_kind":"Disorder","disease_name":"Dilated Cardiomyopathy 1U","disease_synonyms":["CMD1U","DCM1U","cardiomyopathy, dilated, 1U","dilated cardiomyopathy type 1U","PSEN1-related dilated cardiomyopathy","familial isolated dilated cardiomyopathy caused by mutation in PSEN1"],"disease_term":{"id":"MONDO:0013371","label":"dilated cardiomyopathy 1U","display_label":"dilated cardiomyopathy 1U","url":"http://purl.obolibrary.org/obo/MONDO_0013371"},"experimental_model_type":"IPSC_DERIVED_MODEL","experimental_model_type_label":"iPSC-derived model","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},"organism_label":"Homo sapiens","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[{"id":"UBERON:0002084","label":"heart left ventricle","display_label":"left ventricle","url":"http://purl.obolibrary.org/obo/UBERON_0002084"}],"linked_anatomy_labels":["heart left ventricle"],"anatomy":[{"id":"UBERON:0002084","label":"heart left ventricle","display_label":"left ventricle","url":"http://purl.obolibrary.org/obo/UBERON_0002084"}],"anatomy_labels":["heart left ventricle"],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[{"id":"CL:0000746","label":"cardiac muscle cell","display_label":"Cardiomyocyte","url":"http://purl.obolibrary.org/obo/CL_0000746"}],"linked_cell_type_labels":["cardiac muscle cell"],"cell_types":[{"id":"CL:0000746","label":"cardiac muscle cell","display_label":"Cardiomyocyte","url":"http://purl.obolibrary.org/obo/CL_0000746"}],"cell_type_labels":["cardiac muscle cell"],"conditions":[],"cell_source":null,"source_category":"iPSC-derived","culture_system":null,"publication":"PMID:38851626","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38851626","mechanisms":[{"target":"Dysregulated Cardiomyocyte Calcium Handling","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy_1U.html#pathophysiology-dysregulated-cardiomyocyte-calcium-handling","relationship":"PARTIALLY_RECAPITULATES","relationship_label":"Partially Recapitulates","fidelity":"LOW","fidelity_label":"Low","description":"Demonstrates that a PSEN1 variant produces a specific, mechanistically characterised calcium-handling defect in human cardiomyocytes, which is the class of result this node needs and has otherwise never had.","limitations":"Different allele, different disease and different ascertainment: PSEN1 delta-exon-9 causes familial Alzheimer disease and these donors were not dilated-cardiomyopathy patients, so nothing here shows that Asp333Gly behaves the same way. The defect is an SR leak rather than the SERCA2a-uptake failure the human myocardial work implicates, and it left electrophysiological properties unchanged, so it is not obviously a route to a dilated phenotype. iPSC-derived cardiomyocytes are also immature relative to adult myocardium.","biological_scale":"CELLULAR","anatomy":[{"id":"UBERON:0002084","label":"heart left ventricle","display_label":"left ventricle","url":"http://purl.obolibrary.org/obo/UBERON_0002084"}],"cell_types":[{"id":"CL:0000746","label":"cardiac muscle cell","display_label":"Cardiomyocyte","url":"http://purl.obolibrary.org/obo/CL_0000746"}],"biological_processes":[{"id":"GO:0070588","label":"calcium ion transmembrane transport","display_label":"calcium ion transmembrane transport","url":"http://purl.obolibrary.org/obo/GO_0070588"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Sarcoplasmic reticulum calcium leak against isogenic control","description":null,"target":"Dysregulated Cardiomyocyte Calcium Handling","direction":"INCREASED","interpretation":"The core measurement, made against an isogenic control so the comparison is clean, and pharmacologically dissected: the leak survives blockade of both ryanodine and IP3 receptors, so it is not through either channel.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:38851626","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38851626","reference_title":"Presenilin-1 ΔE9 mutation associated sarcoplasmic reticulum leak alters [Ca(2+)](i) distribution in human iPSC-derived cardiomyocytes.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"When compared with their isogenic controls, PSEN1 ΔE9 cardiomyocytes showed increased sarcoplasmic reticulum (SR) Ca2+ leak that was resistant to blockage of ryanodine receptors (RyRs) by tetracaine or inositol-3-reseceptors (IP3Rs) by 2-ABP.","explanation":"The leak measurement and the two pharmacological controls that exclude the obvious channels."}],"notes":null},{"name":"Electrophysiological properties of the cardiomyocytes","description":null,"target":"Dysregulated Cardiomyocyte Calcium Handling","direction":"UNCHANGED","interpretation":"A negative result worth recording: the calcium leak did not change the cells' electrophysiology, so whatever this variant does to a cardiomyocyte it does not do it through the action potential.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:38851626","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38851626","reference_title":"Presenilin-1 ΔE9 mutation associated sarcoplasmic reticulum leak alters [Ca(2+)](i) distribution in human iPSC-derived cardiomyocytes.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The SR Ca2+ leak did not affect electrophysiological properties of the hiPSC-CMs","explanation":"The measured absence of an electrophysiological effect."}],"notes":null}],"evidence":[{"reference":"PMID:38851626","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38851626","reference_title":"Presenilin-1 ΔE9 mutation associated sarcoplasmic reticulum leak alters [Ca(2+)](i) distribution in human iPSC-derived cardiomyocytes.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"When compared with their isogenic controls, PSEN1 ΔE9 cardiomyocytes showed increased sarcoplasmic reticulum (SR) Ca2+ leak that was resistant to blockage of ryanodine receptors (RyRs) by tetracaine or inositol-3-reseceptors (IP3Rs) by 2-ABP.","explanation":"The leak measurement and the two pharmacological controls that exclude the obvious channels."},{"reference":"PMID:38851626","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38851626","reference_title":"Presenilin-1 ΔE9 mutation associated sarcoplasmic reticulum leak alters [Ca(2+)](i) distribution in human iPSC-derived cardiomyocytes.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The SR Ca2+ leak did not affect electrophysiological properties of the hiPSC-CMs","explanation":"The measured absence of an electrophysiological effect."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Dilated_Cardiomyopathy_1U","model_node_id":"model:kb/disorders/Dilated_Cardiomyopathy_1U.yaml:PSEN1 delta-exon-9 patient iPSC-derived cardiomyocytes","focus_node_id":"node:disorder%3ADilated_Cardiomyopathy_1U:pathophysiology:Dysregulated%20Cardiomyocyte%20Calcium%20Handling","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy_1U.html#pathograph","nodes":[{"id":"model:kb/disorders/Dilated_Cardiomyopathy_1U.yaml:PSEN1 delta-exon-9 patient iPSC-derived cardiomyocytes","kind":"experimental_model","kind_label":"NAM model","label":"PSEN1 delta-exon-9 patient iPSC-derived cardiomyocytes","description":"Cardiomyocytes differentiated from induced pluripotent stem cells of patients carrying the PSEN1 exon 9 deletion, compared against isogenic controls. 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So this system does not resolve the tissue mismatch that this entry's central hypothesis rests on - it narrows it, by showing that a PSEN1 variant can disturb cardiomyocyte calcium in human cells, while leaving open whether the CMD1U allele does.","url":"https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy_1U.html#experimental-model-psen1-delta-exon-9-patient-ipsc-derived-cardiomyocytes","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ADilated_Cardiomyopathy_1U:pathophysiology:Dysregulated%20Cardiomyocyte%20Calcium%20Handling","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Dysregulated Cardiomyocyte Calcium Handling","description":"The proposed effector step: disturbed intracellular calcium regulation in the cardiomyocyte. Two separate observations point at it, and neither was made in a cardiomyocyte carrying the CMD1U allele.\nFirst, cultured skin fibroblasts from PSEN1 and PSEN2 mutation carriers in the founding families showed altered calcium signalling. Fibroblasts are an accessible surrogate, not a contractile cell, and the paper reports the abnormality without asserting a myocardial equivalent.\nSecond, presenilin-1 co-immunoprecipitates with SERCA2a, the cardiac sarcoplasmic-reticulum calcium ATPase, in explanted idiopathic dilated cardiomyopathy hearts. That is a physical association in human myocardium and is the most cardiac-specific molecular result in this literature. It is an interaction, not a rate: no measurement of SERCA2a activity in a PSEN1-variant heart exists, so the node carries no direction. The biological process below is tagged DYSREGULATED rather than INCREASED or DECREASED for that reason - the sources say \"altered\", and choosing a direction would be an invention.","url":"https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy_1U.html#pathophysiology-dysregulated-cardiomyocyte-calcium-handling","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"HYPOTHETICAL","mechanism_confidence_label":"Hypothetical"},{"id":"node:disorder%3ADilated_Cardiomyopathy_1U:pathophysiology:PSEN1%20Asp333Gly%20Missense%20Variant%20in%20Cardiomyocytes","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"PSEN1 Asp333Gly Missense Variant in Cardiomyocytes","description":"A heterozygous germline PSEN1 missense variant, Asp333Gly, in the large hydrophilic cytoplasmic loop between transmembrane domains six and seven of presenilin-1. Presenilin-1 is expressed in myocardium as well as brain, so a cardiomyocyte-autonomous lesion is anatomically possible, and the founding study reported the variant segregating with aggressive dilated cardiomyopathy in one family.\nWhat the variant does to presenilin-1 in a cardiomyocyte has never been measured. There is no structural or biochemical characterisation of D333G in cardiac tissue, no D333G cardiomyocyte model, and no directional statement available about gamma-secretase activity in the heart of a carrier. The node is therefore typed as the proposed initiating lesion and given no modifier and no functional_impact_category: FunctionalImpactEnum has no value that would be honest here, since neither loss nor gain of function has been shown for this allele in this tissue.\nA second, independent PSEN1 lesion has been described in myocardium and is placed at the same point in the chain: two promoter-region variants found in sporadic idiopathic dilated cardiomyopathy that reduce presenilin-1 transcription and protein in the myocardium. These are a different genetic mechanism in different patients, not the CMD1U allele, and they are recorded here because they are the expression evidence ClinGen names as the only surviving support for a PSEN1-heart relationship.","url":"https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy_1U.html#pathophysiology-psen1-asp333gly-missense-variant-in-cardiomyocytes","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"HYPOTHETICAL","mechanism_confidence_label":"Hypothetical"},{"id":"node:disorder%3ADilated_Cardiomyopathy_1U:pathophysiology:Ventricular%20Remodeling%20and%20Chamber%20Dilatation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Ventricular Remodeling and Chamber Dilatation","description":"Adverse structural remodeling of the left ventricle - chamber dilatation with wall thinning - as the shared final common path of the cardiomyopathies. Nothing in the CMD1U literature characterises remodeling in a PSEN1 carrier heart specifically: there is no histology, no fibrosis quantification, and no imaging series. The node is curated because the reported clinical phenotype is dilated cardiomyopathy and this is the step that word names, and it conforms to the shared module rather than claiming disease-specific detail.","url":"https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy_1U.html#pathophysiology-ventricular-remodeling-and-chamber-dilatation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Dilated_Cardiomyopathy_1U.yaml:PSEN1 delta-exon-9 patient iPSC-derived cardiomyocytes","source_id":"model:kb/disorders/Dilated_Cardiomyopathy_1U.yaml:PSEN1 delta-exon-9 patient iPSC-derived cardiomyocytes","target_id":"node:disorder%3ADilated_Cardiomyopathy_1U:pathophysiology:Dysregulated%20Cardiomyocyte%20Calcium%20Handling","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Partially Recapitulates","directed":false,"relationship":"PARTIALLY_RECAPITULATES","fidelity":"LOW","causal_link_type":null,"causal_link_type_label":null,"description":"Demonstrates that a PSEN1 variant produces a specific, mechanistically characterised calcium-handling defect in human cardiomyocytes, which is the class of result this node needs and has otherwise never had.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ADilated_Cardiomyopathy_1U:1:0","source_id":"node:disorder%3ADilated_Cardiomyopathy_1U:pathophysiology:Dysregulated%20Cardiomyocyte%20Calcium%20Handling","target_id":"node:disorder%3ADilated_Cardiomyopathy_1U:pathophysiology:Ventricular%20Remodeling%20and%20Chamber%20Dilatation","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[0]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"Impaired excitation-contraction coupling as a chronic cardiomyocyte insult driving adverse remodeling. 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Its support is calcium signalling measured in cultured skin fibroblasts from carriers, not in cardiomyocytes, so the intermediates between the variant and a myocardial calcium defect are unknown.","intermediate_mechanisms":[],"hypothesis_groups":["psen1_calcium_handling_dcm"],"evidence_count":0}]}}],"mechanism_names":["Dysregulated Cardiomyocyte Calcium Handling"],"relationships":["Partially Recapitulates"],"fidelities":["Low"],"biological_scales":["Cellular"],"system_context_sources":["Linked mechanism anatomy","Linked mechanism cell type","Linked mechanism biological scale"],"modeled_system_labels":["heart left ventricle","cardiac muscle cell","Cellular"],"biological_process_terms":[{"id":"GO:0070588","label":"calcium ion transmembrane transport","display_label":"calcium ion transmembrane transport","url":"http://purl.obolibrary.org/obo/GO_0070588"}],"biological_processes":["calcium ion transmembrane transport"],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":["Sarcoplasmic reticulum calcium leak against isogenic control","Electrophysiological properties of the cardiomyocytes"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:38851626","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38851626","reference_title":"Presenilin-1 ΔE9 mutation associated sarcoplasmic reticulum leak alters [Ca(2+)](i) distribution in human iPSC-derived cardiomyocytes.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"This demonstrates that PSEN1 ΔE9 induced SR Ca2+ leak has specific effects in iPSC-CMs, reflecting their unique structural and calcium signaling features.","explanation":"The authors' conclusion that the leak is a cardiomyocyte-specific effect rather than a generic consequence of the variant, which is what makes this system informative for a cardiac entry at all. The sentence stating the leak's functional consequence - diastolic calcium buildup near the perinuclear SR with less releasable calcium during systole - is described in this entry's prose rather than quoted, because its bracketed calcium notation is stripped by the reference validator's bracket handling and so cannot be snippet-verified."},{"reference":"PMID:38851626","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38851626","reference_title":"Presenilin-1 ΔE9 mutation associated sarcoplasmic reticulum leak alters [Ca(2+)](i) distribution in human iPSC-derived cardiomyocytes.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"When compared with their isogenic controls, PSEN1 ΔE9 cardiomyocytes showed increased sarcoplasmic reticulum (SR) Ca2+ leak that was resistant to blockage of ryanodine receptors (RyRs) by tetracaine or inositol-3-reseceptors (IP3Rs) by 2-ABP.","explanation":"The leak measurement and the two pharmacological controls that exclude the obvious channels."},{"reference":"PMID:38851626","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38851626","reference_title":"Presenilin-1 ΔE9 mutation associated sarcoplasmic reticulum leak alters [Ca(2+)](i) distribution in human iPSC-derived cardiomyocytes.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The SR Ca2+ leak did not affect electrophysiological properties of the hiPSC-CMs","explanation":"The measured absence of an electrophysiological effect."}],"evidence_text":["This demonstrates that PSEN1 ΔE9 induced SR Ca2+ leak has specific effects in iPSC-CMs, reflecting their unique structural and calcium signaling features.","When compared with their isogenic controls, PSEN1 ΔE9 cardiomyocytes showed increased sarcoplasmic reticulum (SR) Ca2+ leak that was resistant to blockage of ryanodine receptors (RyRs) by tetracaine or inositol-3-reseceptors (IP3Rs) by 2-ABP.","The SR Ca2+ leak did not affect electrophysiological properties of the hiPSC-CMs","The authors' conclusion that the leak is a cardiomyocyte-specific effect rather than a generic consequence of the variant, which is what makes this system informative for a cardiac entry at all. The sentence stating the leak's functional consequence - diastolic calcium buildup near the perinuclear SR with less releasable calcium during systole - is described in this entry's prose rather than quoted, because its bracketed calcium notation is stripped by the reference validator's bracket handling and so cannot be snippet-verified.","The leak measurement and the two pharmacological controls that exclude the obvious channels.","The measured absence of an electrophysiological effect."],"evidence_status":"Evidence recorded","metadata_completeness":70,"metadata_present":["Model category","Organism","Anatomy","Cell type","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Cell source","Culture system"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Dilated_Cardiomyopathy_1U.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dilated_Cardiomyopathy_1U.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy_1U.html#experimental-model-psen1-delta-exon-9-patient-ipsc-derived-cardiomyocytes","source_anchor":"experimental-model-psen1-delta-exon-9-patient-ipsc-derived-cardiomyocytes"},{"id":"model:kb/disorders/Bannayan-Riley-Ruvalcaba_Syndrome.yaml:PTEN lipid-phosphatase biochemical and 293-cell assays","name":"PTEN lipid-phosphatase biochemical and 293-cell assays","description":"Recombinant protein assays establish PIP3 dephosphorylation at position 3. 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PTEN germline mutations account for ~0.2-1% of all autism spectrum disorder (ASD) cases, ~17% of ASD with macrocephaly, and ~20-23% of PHTS individuals are diagnosed with ASD.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Cowden_Syndrome.html#pathophysiology-neurodevelopmental-cortical-dysfunction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACowden_Syndrome:pathophysiology:Increased%20Cancer%20Risk","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Increased Cancer Risk","description":"The same PI3K/AKT/mTOR over-activation that drives benign hamartoma formation also confers markedly elevated lifetime risks for malignancies. 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Second-hit somatic mutations or epigenetic silencing of the remaining wild-type PTEN allele accelerate neoplastic progression.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Cowden_Syndrome.html#pathophysiology-increased-cancer-risk","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACowden_Syndrome:pathophysiology:PTEN%20Genome%20Integrity%20Defect","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"PTEN Genome Integrity Defect","description":"Beyond its well-known role as a lipid phosphatase, PTEN performs nuclear functions in maintaining genome integrity, including DNA double-strand break repair and chromosomal stability. Quantitative DNA damage response (DDR) modeling of PHTS patient-derived lymphoblastoid cell lines (n=43) shows that PTEN nonsense variants have less efficient DNA repair (higher residual gamma-H2AX foci 24 h after irradiation) than missense variants, and that DDR dynamics differ between PHTS-ASD/DD and PHTS-cancer phenotypic subgroups. This second molecular axis (genome instability) likely contributes to the pleiotropy of PHTS — explaining why cancer and neurodevelopmental phenotypes can both arise from germline PTEN loss without simply scaling with PI3K/AKT/mTOR over-activation.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Cowden_Syndrome.html#pathophysiology-pten-genome-integrity-defect","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACowden_Syndrome:pathophysiology:PTEN%20Loss%20and%20PI3K%2FAKT%2FmTOR%20Pathway%20Activation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"PTEN Loss and PI3K/AKT/mTOR Pathway Activation","description":"PTEN (phosphatase and tensin homolog) is a tumor suppressor that dephosphorylates phosphatidylinositol-3,4,5-trisphosphate (PIP3) to PIP2, thereby inhibiting the PI3K/AKT/mTOR signaling axis. Germline loss-of-function mutations in PTEN lead to constitutive accumulation of PIP3 and unopposed activation of AKT and downstream mTOR complex 1 (mTORC1), resulting in excessive cell proliferation, survival, and growth that underlies hamartoma formation and elevated cancer risk across multiple organ systems.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Cowden_Syndrome.html#pathophysiology-pten-loss-and-pi3k-akt-mtor-pathway-activation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Cowden_Syndrome.yaml:PTEN-mutant iPSC-derived forebrain organoids","source_id":"model:kb/disorders/Cowden_Syndrome.yaml:PTEN-mutant iPSC-derived forebrain organoids","target_id":"node:disorder%3ACowden_Syndrome:pathophysiology:Neurodevelopmental%20Cortical%20Dysfunction","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"Human germline-PTEN-genotype cells reproduce disrupted neuronal differentiation, radial glial positioning and cortical layering during early forebrain development.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ACowden_Syndrome:4:0","source_id":"node:disorder%3ACowden_Syndrome:pathophysiology:Neurodevelopmental%20Cortical%20Dysfunction","target_id":"node:disorder%3ACowden_Syndrome:pathophysiology:Increased%20Cancer%20Risk","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[4].downstream[0]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ACowden_Syndrome:3:1","source_id":"node:disorder%3ACowden_Syndrome:pathophysiology:PTEN%20Genome%20Integrity%20Defect","target_id":"node:disorder%3ACowden_Syndrome:pathophysiology:Neurodevelopmental%20Cortical%20Dysfunction","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[3].downstream[1]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ACowden_Syndrome:0:2","source_id":"node:disorder%3ACowden_Syndrome:pathophysiology:PTEN%20Loss%20and%20PI3K%2FAKT%2FmTOR%20Pathway%20Activation","target_id":"node:disorder%3ACowden_Syndrome:pathophysiology:Neurodevelopmental%20Cortical%20Dysfunction","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[2]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1}]}},{"target":"PTEN Loss and PI3K/AKT/mTOR Pathway Activation","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Cowden_Syndrome.html#pathophysiology-pten-loss-and-pi3k-akt-mtor-pathway-activation","relationship":"RESCUES","relationship_label":"Rescues","fidelity":"MODERATE","fidelity_label":"Moderate","description":"Pharmacological AKT inhibition with perifosine reduced over-activated AKT and partially corrected the cellular disorganisation in PTEN G132D organoids. This is the entry's only demonstration that the downstream pathway state, rather than PTEN itself, is what produces the cellular phenotype - and it is in human tissue.","limitations":"Correction was partial, not complete, and was shown for the G132D allele only. Perifosine is not a Cowden syndrome treatment and the experiment says nothing about clinical benefit; it is a mechanistic rescue, and the one randomised trial of pathway inhibition in patients missed its primary endpoint.","biological_scale":null,"anatomy":[],"cell_types":[{"id":"CL:0000066","label":"epithelial cell","display_label":"Epithelial cell","url":"http://purl.obolibrary.org/obo/CL_0000066"},{"id":"CL:0000057","label":"fibroblast","display_label":"Fibroblast","url":"http://purl.obolibrary.org/obo/CL_0000057"}],"biological_processes":[{"id":"GO:0043491","label":"phosphatidylinositol 3-kinase/protein kinase B signal transduction","display_label":"PI3K/AKT signaling","url":"http://purl.obolibrary.org/obo/GO_0043491"},{"id":"GO:0031929","label":"TOR signaling","display_label":"TOR signaling","url":"http://purl.obolibrary.org/obo/GO_0031929"},{"id":"GO:0008283","label":"cell population proliferation","display_label":"Cell proliferation","url":"http://purl.obolibrary.org/obo/GO_0008283"},{"id":"GO:0043066","label":"negative regulation of apoptotic process","display_label":"Negative regulation of apoptosis","url":"http://purl.obolibrary.org/obo/GO_0043066"}],"pathways":[],"genes":[{"id":"hgnc:9588","label":"PTEN","display_label":"PTEN","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/9588"},{"id":"hgnc:8975","label":"PIK3CA","display_label":"PIK3CA","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/8975"},{"id":"hgnc:391","label":"AKT1","display_label":"AKT1","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/391"}],"chemicals":[],"readouts":[{"name":"AKT activation and cellular organisation after perifosine","description":null,"target":"PTEN Loss and PI3K/AKT/mTOR Pathway Activation","direction":"RESTORED","interpretation":"Over-activated AKT falls and the disrupted cellular organisation is partially corrected, in the same organoid system that showed the defect.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:38030818","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38030818","reference_title":"Germline PTEN genotype-dependent phenotypic divergence during the early neural developmental process of forebrain organoids.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Perifosine, an AKT inhibitor, reduced over-activated AKT and partially corrected the abnormalities in cellular organization observed in PTENG132D organoids.","explanation":"Reports both measured quantities - AKT activation and cellular organisation - and states the correction was partial."}],"notes":null}],"evidence":[{"reference":"PMID:38030818","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38030818","reference_title":"Germline PTEN genotype-dependent phenotypic divergence during the early neural developmental process of forebrain organoids.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Single cell RNAseq analyses on early-stage organoids revealed that genes related to neural cell fate were decreased in PTENG132D mutant organoids, and AKT inhibition was capable of upregulating gene signatures related to neuronal cell fate and CNS maturation pathways.","explanation":"Establishes the model as informative for the pathway-activation node, on a separate measurement from the readout below: inhibiting AKT moves the transcriptional programme, not only the cellular morphology. The two layers make different claims and now rest on different sentences."},{"reference":"PMID:38030818","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38030818","reference_title":"Germline PTEN genotype-dependent phenotypic divergence during the early neural developmental process of forebrain organoids.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Perifosine, an AKT inhibitor, reduced over-activated AKT and partially corrected the abnormalities in cellular organization observed in PTENG132D organoids.","explanation":"Reports both measured quantities - AKT activation and cellular organisation - and states the correction was partial."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Cowden_Syndrome","model_node_id":"model:kb/disorders/Cowden_Syndrome.yaml:PTEN-mutant iPSC-derived forebrain organoids","focus_node_id":"node:disorder%3ACowden_Syndrome:pathophysiology:PTEN%20Loss%20and%20PI3K%2FAKT%2FmTOR%20Pathway%20Activation","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Cowden_Syndrome.html#pathograph","nodes":[{"id":"model:kb/disorders/Cowden_Syndrome.yaml:PTEN-mutant iPSC-derived forebrain organoids","kind":"experimental_model","kind_label":"NAM model","label":"PTEN-mutant iPSC-derived forebrain organoids","description":"Forebrain organoids differentiated from gene-edited isogenic iPSCs carrying one of two germline PTEN missense alleles - G132D, associated with autism, and M134R, associated with cancer. The entry already cited this work as evidence on the neurodevelopmental node; it is modelled here as a system so the node carries the fidelity and limitations of the evidence, not only its conclusion. Its distinctive value is stage resolution, and the finding that resolution produced: the two alleles do not act at the same point. G132D disrupts neuroectoderm formation within the first several days, while M134R is morphologically normal then and diverges only later. Both converge on disrupted differentiation, radial glia positioning and cortical layering by 72+ days. This is human tissue, which the mouse models are not.","url":"https://dismech.monarchinitiative.org/pages/disorders/Cowden_Syndrome.html#experimental-model-pten-mutant-ipsc-derived-forebrain-organoids","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACowden_Syndrome:pathophysiology:PTEN%20Loss%20and%20PI3K%2FAKT%2FmTOR%20Pathway%20Activation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"PTEN Loss and PI3K/AKT/mTOR Pathway Activation","description":"PTEN (phosphatase and tensin homolog) is a tumor suppressor that dephosphorylates phosphatidylinositol-3,4,5-trisphosphate (PIP3) to PIP2, thereby inhibiting the PI3K/AKT/mTOR signaling axis. Germline loss-of-function mutations in PTEN lead to constitutive accumulation of PIP3 and unopposed activation of AKT and downstream mTOR complex 1 (mTORC1), resulting in excessive cell proliferation, survival, and growth that underlies hamartoma formation and elevated cancer risk across multiple organ systems.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Cowden_Syndrome.html#pathophysiology-pten-loss-and-pi3k-akt-mtor-pathway-activation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACowden_Syndrome:pathophysiology:Hamartoma%20Formation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Hamartoma Formation","description":"Constitutive activation of PI3K/AKT/mTOR signaling in multiple cell lineages drives the abnormal but organized proliferation of tissue elements native to the affected site, producing hamartomas. In Cowden syndrome these manifest as mucocutaneous trichilemmomas, papillomatous papules, acral keratoses, gastrointestinal hamartomatous polyps, and thyroid adenomas. The hamartomas are histologically benign but serve as a marker of systemic PTEN dysfunction and elevated cancer predisposition.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Cowden_Syndrome.html#pathophysiology-hamartoma-formation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACowden_Syndrome:pathophysiology:Increased%20Cancer%20Risk","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Increased Cancer Risk","description":"The same PI3K/AKT/mTOR over-activation that drives benign hamartoma formation also confers markedly elevated lifetime risks for malignancies. The cumulative lifetime risk in PTEN mutation carriers includes breast cancer (~77-85%), follicular/papillary thyroid cancer (~35-38%), endometrial cancer (~28%), renal cell carcinoma (~34%), and colorectal cancer (~9-16%). Second-hit somatic mutations or epigenetic silencing of the remaining wild-type PTEN allele accelerate neoplastic progression.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Cowden_Syndrome.html#pathophysiology-increased-cancer-risk","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACowden_Syndrome:pathophysiology:Neurodevelopmental%20Cortical%20Dysfunction","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Neurodevelopmental Cortical Dysfunction","description":"In addition to its cell-autonomous role in restraining cell growth, PTEN regulates neuronal differentiation, dendritic arborisation, and synaptic homeostasis. Germline PTEN loss causes early-stage neuroectoderm and forebrain organoid abnormalities (disrupted neuronal differentiation, radial glia mispositioning, and altered cortical layering) and contributes to macrocephaly and autism-spectrum neurobehavioral phenotypes through PI3K/AKT/mTOR over-activation in cortical progenitors and neurons. PTEN germline mutations account for ~0.2-1% of all autism spectrum disorder (ASD) cases, ~17% of ASD with macrocephaly, and ~20-23% of PHTS individuals are diagnosed with ASD.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Cowden_Syndrome.html#pathophysiology-neurodevelopmental-cortical-dysfunction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACowden_Syndrome:pathophysiology:Reduced%20Succinate%20Dehydrogenase%20Activity","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced Succinate Dehydrogenase Activity","description":"A proposed convergent node, carried explicitly as a hypothesis. Cowden and Cowden-like syndrome have genetically unrelated causes - PTEN loss, KLLN promoter hypermethylation, and SDHB/SDHD variants - and this node is the only account on offer for why they produce clinically indistinguishable disease. SDHx variants reduce succinate dehydrogenase activity by definition; the claim that PTEN loss does so as well rests on a single study of 21 carriers that measured plasma succinate and inferred the enzyme. Nothing downstream is drawn from this node, because what the accumulated succinate would then do in Cowden syndrome has not been shown.","url":"https://dismech.monarchinitiative.org/pages/disorders/Cowden_Syndrome.html#pathophysiology-reduced-succinate-dehydrogenase-activity","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:1:model:kb/disorders/Cowden_Syndrome.yaml:PTEN-mutant iPSC-derived forebrain organoids","source_id":"model:kb/disorders/Cowden_Syndrome.yaml:PTEN-mutant iPSC-derived forebrain organoids","target_id":"node:disorder%3ACowden_Syndrome:pathophysiology:PTEN%20Loss%20and%20PI3K%2FAKT%2FmTOR%20Pathway%20Activation","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[1]","label":"Rescues","directed":false,"relationship":"RESCUES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"Pharmacological AKT inhibition with perifosine reduced over-activated AKT and partially corrected the cellular disorganisation in PTEN G132D organoids. 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The isogenic design is what makes the genotype, rather than donor background, the variable under study."},{"reference":"PMID:38030818","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38030818","reference_title":"Germline PTEN genotype-dependent phenotypic divergence during the early neural developmental process of forebrain organoids.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"we observed disrupted neuronal differentiation, radial glia positioning, and cortical layering in both PTEN-mutant organoids at the later stage of 72+ days of development.","explanation":"Names the three measured readouts and the differentiation stage at which they diverge."},{"reference":"PMID:38030818","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38030818","reference_title":"Germline PTEN genotype-dependent phenotypic divergence during the early neural developmental process of forebrain organoids.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Single cell RNAseq analyses on early-stage organoids revealed that genes related to neural cell fate were decreased in PTENG132D mutant organoids, and AKT inhibition was capable of upregulating gene signatures related to neuronal cell fate and CNS maturation pathways.","explanation":"Establishes the model as informative for the pathway-activation node, on a separate measurement from the readout below: inhibiting AKT moves the transcriptional programme, not only the cellular morphology. The two layers make different claims and now rest on different sentences."},{"reference":"PMID:38030818","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38030818","reference_title":"Germline PTEN genotype-dependent phenotypic divergence during the early neural developmental process of forebrain organoids.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Perifosine, an AKT inhibitor, reduced over-activated AKT and partially corrected the abnormalities in cellular organization observed in PTENG132D organoids.","explanation":"Reports both measured quantities - AKT activation and cellular organisation - and states the correction was partial."}],"evidence_text":["We generated forebrain organoid cultures from gene-edited isogenic human induced pluripotent stem cells (hiPSCs) harboring a PTENG132D (ASD) or PTENM134R (cancer) mutant allele to model how these mutations interrupt neurodevelopmental processes.","we observed disrupted neuronal differentiation, radial glia positioning, and cortical layering in both PTEN-mutant organoids at the later stage of 72+ days of development.","Single cell RNAseq analyses on early-stage organoids revealed that genes related to neural cell fate were decreased in PTENG132D mutant organoids, and AKT inhibition was capable of upregulating gene signatures related to neuronal cell fate and CNS maturation pathways.","Perifosine, an AKT inhibitor, reduced over-activated AKT and partially corrected the abnormalities in cellular organization observed in PTENG132D organoids.","States what the model is and that it was built to model germline PTEN disruption of neurodevelopment, which is the claim a link-level evidence item should make. The isogenic design is what makes the genotype, rather than donor background, the variable under study.","Names the three measured readouts and the differentiation stage at which they diverge.","Establishes the model as informative for the pathway-activation node, on a separate measurement from the readout below: inhibiting AKT moves the transcriptional programme, not only the cellular morphology. 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In mice, a genetic expression reporter localized Cabp2 to inner and outer hair cells but not spiral ganglion neurons, supporting a presynaptic site of the principal sound-encoding defect.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Recessive_Nonsyndromic_Hearing_Loss_93.html#pathophysiology-loss-of-cabp2-function-at-the-inner-hair-cell-ribbon-synapse","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAutosomal_Recessive_Nonsyndromic_Hearing_Loss_93:pathophysiology:Biallelic%20CABP2%20Loss-of-Function%20Variant","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Biallelic CABP2 Loss-of-Function Variant","description":"Biallelic pathogenic CABP2 variants impair CaBP2 function. Reported alleles include splice-site, nonsense and missense variants. For the recurrent c.637+1G>T allele, exon skipping was demonstrated in a minigene assay and truncation is predicted if the abnormal transcript escapes nonsense-mediated decay; endogenous mutant protein abundance in patient hair cells was not measured.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Recessive_Nonsyndromic_Hearing_Loss_93.html#pathophysiology-biallelic-cabp2-loss-of-function-variant","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAutosomal_Recessive_Nonsyndromic_Hearing_Loss_93:pathophysiology:CABP2%20Exon%206%20Skipping","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"CABP2 Exon 6 Skipping","description":"The recurrent c.637+1G>T allele disrupts splicing in a COS-7 exon-trapping assay. Skipping exon 6 predicts a frameshift, p.Phe164Serfs*4, and loss of the last two EF hands if the RNA escapes degradation. This assay establishes a splice defect, not the abundance or stability of the transcript in human inner hair cells.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Recessive_Nonsyndromic_Hearing_Loss_93.html#pathophysiology-cabp2-exon-6-skipping","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAutosomal_Recessive_Nonsyndromic_Hearing_Loss_93:pathophysiology:Enhanced%20CaV1.3%20Calcium-Channel%20Inactivation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Enhanced CaV1.3 Calcium-Channel Inactivation","description":"Cabp2-deficient mouse inner hair cells show increased CaV1.3 inactivation despite preserved peak calcium-current amplitude and voltage dependence of activation under the tested conditions. At room temperature, the single knockout primarily increases voltage-dependent inactivation; its increase in calcium-dependent inactivation did not reach significance. Removing both CaBP1 and CaBP2 markedly enhances both components. Normal peak current does not directly measure channel number, and double-knockout effects do not establish the magnitude of a CABP2-only human defect.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Recessive_Nonsyndromic_Hearing_Loss_93.html#pathophysiology-enhanced-cav1-3-calcium-channel-inactivation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Autosomal_Recessive_Nonsyndromic_Hearing_Loss_93.yaml:Purified CaBP2 calcium-binding assay","source_id":"model:kb/disorders/Autosomal_Recessive_Nonsyndromic_Hearing_Loss_93.yaml:Purified CaBP2 calcium-binding assay","target_id":"node:disorder%3AAutosomal_Recessive_Nonsyndromic_Hearing_Loss_93:pathophysiology:Loss%20of%20CaBP2%20Function%20at%20the%20Inner%20Hair%20Cell%20Ribbon%20Synapse","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Measures","directed":false,"relationship":"MEASURES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AAutosomal_Recessive_Nonsyndromic_Hearing_Loss_93:0:1","source_id":"node:disorder%3AAutosomal_Recessive_Nonsyndromic_Hearing_Loss_93:pathophysiology:Biallelic%20CABP2%20Loss-of-Function%20Variant","target_id":"node:disorder%3AAutosomal_Recessive_Nonsyndromic_Hearing_Loss_93:pathophysiology:Loss%20of%20CaBP2%20Function%20at%20the%20Inner%20Hair%20Cell%20Ribbon%20Synapse","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[1]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Other pathogenic alleles can impair CaBP2 function through mechanisms that need not involve exon 6 skipping.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3AAutosomal_Recessive_Nonsyndromic_Hearing_Loss_93:1:0","source_id":"node:disorder%3AAutosomal_Recessive_Nonsyndromic_Hearing_Loss_93:pathophysiology:CABP2%20Exon%206%20Skipping","target_id":"node:disorder%3AAutosomal_Recessive_Nonsyndromic_Hearing_Loss_93:pathophysiology:Loss%20of%20CaBP2%20Function%20at%20the%20Inner%20Hair%20Cell%20Ribbon%20Synapse","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"The predicted truncation removes C-terminal EF hands. An engineered p.Phe164Ter proxy has altered calcium binding and weakened, residual CaV1.3 regulation.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3AAutosomal_Recessive_Nonsyndromic_Hearing_Loss_93:2:0","source_id":"node:disorder%3AAutosomal_Recessive_Nonsyndromic_Hearing_Loss_93:pathophysiology:Loss%20of%20CaBP2%20Function%20at%20the%20Inner%20Hair%20Cell%20Ribbon%20Synapse","target_id":"node:disorder%3AAutosomal_Recessive_Nonsyndromic_Hearing_Loss_93:pathophysiology:Enhanced%20CaV1.3%20Calcium-Channel%20Inactivation","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"CaBP2's specific action is to suppress inactivation; without it the suppression is lifted.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0}]}}],"mechanism_names":["Loss of CaBP2 Function at the Inner Hair Cell Ribbon Synapse"],"relationships":["Measures"],"fidelities":["Moderate"],"biological_scales":["Molecular"],"system_context_sources":["Linked mechanism cell type","Linked mechanism biological scale"],"modeled_system_labels":["cochlear inner hair cell","Molecular"],"biological_process_terms":[],"biological_processes":[],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":[],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:22981119","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/22981119","reference_title":"A mutation in CABP2, expressed in cochlear hair cells, causes autosomal-recessive hearing impairment.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Compared with wild-type CaBP2, the truncated CaBP2 showed altered Ca(2+) binding in isothermal titration calorimetry","explanation":"Direct biochemical measurement of the engineered proteins."}],"evidence_text":["Compared with wild-type CaBP2, the truncated CaBP2 showed altered Ca(2+) binding in isothermal titration calorimetry","Direct biochemical measurement of the engineered proteins."],"evidence_status":"Evidence recorded","metadata_completeness":40,"metadata_present":["Model category","Cell type","Modeled mechanism","Evidence"],"metadata_missing":["NAMO class","Organism","Anatomy","Cell source","Culture system","Publication"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Autosomal_Recessive_Nonsyndromic_Hearing_Loss_93.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autosomal_Recessive_Nonsyndromic_Hearing_Loss_93.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Recessive_Nonsyndromic_Hearing_Loss_93.html#experimental-model-purified-cabp2-calcium-binding-assay","source_anchor":"experimental-model-purified-cabp2-calcium-binding-assay"},{"id":"model:kb/disorders/Axial_Spondylometaphyseal_Dysplasia.yaml:Purified CFAP410 C-terminal-domain assembly","name":"Purified CFAP410 C-terminal-domain assembly","description":"Synthetic human, trypanosome and algal C-terminal domains were studied by crystallography, light scattering, size-exclusion chromatography and circular dichroism.","notes":"The p.Leu224Pro variant comes from the broader CFAP410 skeletal-ciliopathy spectrum; 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In NEK1-knockout cells, both wild-type and kinase-dead NEK1 restored CFAP410 abundance, whereas association-defective variants did not; kinase activity and complex-dependent abundance are therefore separable requirements.","url":"https://dismech.monarchinitiative.org/pages/disorders/Axial_Spondylometaphyseal_Dysplasia.html#pathophysiology-disruption-of-the-cfap410-nek1-complex","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAxial_Spondylometaphyseal_Dysplasia:pathophysiology:Biallelic%20CFAP410%20or%20NEK1%20Loss%20of%20Function","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Biallelic CFAP410 or NEK1 Loss of Function","description":"Biallelic CFAP410 variants include missense and splice-altering alleles. 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Complete absence of either protein is not established for every patient genotype.","url":"https://dismech.monarchinitiative.org/pages/disorders/Axial_Spondylometaphyseal_Dysplasia.html#pathophysiology-biallelic-cfap410-or-nek1-loss-of-function","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAxial_Spondylometaphyseal_Dysplasia:pathophysiology:Defective%20Primary%20Ciliogenesis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Defective Primary Ciliogenesis","description":"NEK1 or CFAP410 knockout markedly reduces the proportion of ciliated ARPE-19 cells after serum starvation. Wild-type re-expression rescues ciliogenesis, whereas kinase-dead NEK1 and the association-defective NEK1 p.Asp1277Ala allele do not. These epithelial-cell experiments establish a ciliary function but do not directly assay an axial SMD growth plate or patient photoreceptor.","url":"https://dismech.monarchinitiative.org/pages/disorders/Axial_Spondylometaphyseal_Dysplasia.html#pathophysiology-defective-primary-ciliogenesis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAxial_Spondylometaphyseal_Dysplasia:pathophysiology:Impaired%20Homologous%20Recombination%20Repair","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Homologous Recombination Repair","description":"Depletion of CFAP410 or NEK1 reduces homologous recombination in U2-O-S traffic-light and DR-GFP reporter assays. CFAP410 depletion had little effect on cell-cycle distribution, arguing against a cell-cycle explanation for its repair phenotype. 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Different alleles require their own clinical and functional interpretation; the common p.Tyr131His variant is not treated as a proven cause.","url":"https://dismech.monarchinitiative.org/pages/disorders/ALG6-congenital_disorder_of_glycosylation.html#pathophysiology-biallelic-pathogenic-alg6-variants","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AALG6-Congenital_Disorder_of_Glycosylation:pathophysiology:Incomplete%20Lipid-Linked%20Oligosaccharide%20Glucosylation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Incomplete Lipid-Linked Oligosaccharide Glucosylation","description":"Patient fibroblasts accumulate dolichyl pyrophosphate-Man9GlcNAc2 lacking its normal glucose cap. This is an assembly defect upstream of transfer to protein; residual glucosylation is not excluded.","url":"https://dismech.monarchinitiative.org/pages/disorders/ALG6-congenital_disorder_of_glycosylation.html#pathophysiology-incomplete-lipid-linked-oligosaccharide-glucosylation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/ALG6-Congenital_Disorder_of_Glycosylation.yaml:Purified yeast ALG6 structural and glycosyltransferase assays","source_id":"model:kb/disorders/ALG6-Congenital_Disorder_of_Glycosylation.yaml:Purified yeast ALG6 structural and glycosyltransferase 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precursor.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":2},{"id":"causal:disorder%3AALG6-Congenital_Disorder_of_Glycosylation:0:0","source_id":"node:disorder%3AALG6-Congenital_Disorder_of_Glycosylation:pathophysiology:Biallelic%20Pathogenic%20ALG6%20Variants","target_id":"node:disorder%3AALG6-Congenital_Disorder_of_Glycosylation:pathophysiology:ALG6%20Alpha-1%2C3-Glucosyltransferase%20Deficiency","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"The founding p.Ala333Val allele impairs heterologous complementation while retaining partial function.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":2}]}}],"mechanism_names":["ALG6 Alpha-1,3-Glucosyltransferase Deficiency"],"relationships":["Perturbs"],"fidelities":["Moderate"],"biological_scales":["Molecular"],"system_context_sources":["Linked mechanism biological scale"],"modeled_system_labels":["Molecular"],"biological_process_terms":[],"biological_processes":[],"pathway_terms":[],"pathways":[],"gene_terms":[{"id":"hgnc:23157","label":"ALG6","display_label":"ALG6","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/23157"}],"genes":["ALG6"],"chemical_terms":[],"chemicals":[],"readout_names":["Engineered Asp69 substitution reduces transfer"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:32103179","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/32103179","reference_title":"Structure and mechanism of the ER-based glucosyltransferase ALG6.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The specificity of ALG6 can be demonstrated in vitro, where only glucose, but not mannose, is transferred from a Dol25-P carrier","explanation":"Purified yeast enzyme with synthetic short-chain donor/acceptor substrates, not human patient cells."},{"reference":"PMID:32103179","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/32103179","reference_title":"Structure and mechanism of the ER-based glucosyltransferase ALG6.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Purified ALG6 indeed retains activity in the presence of EDTA","explanation":"Direct biochemical evidence for metal-independent transfer."},{"reference":"PMID:32103179","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/32103179","reference_title":"Structure and mechanism of the ER-based glucosyltransferase ALG6.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Finally, mutating Asp69 to an alanine abolished ALG6 function, and mutating it to an asparagine strongly reduced activity.","explanation":"Engineered active-site perturbation in purified yeast enzyme."}],"evidence_text":["The specificity of ALG6 can be demonstrated in vitro, where only glucose, but not mannose, is transferred from a Dol25-P carrier","Purified ALG6 indeed retains activity in the presence of EDTA","Finally, mutating Asp69 to an alanine abolished ALG6 function, and mutating it to an asparagine strongly reduced activity.","Purified yeast enzyme with synthetic short-chain donor/acceptor substrates, not human patient cells.","Direct biochemical evidence for metal-independent transfer.","Engineered active-site perturbation in purified yeast enzyme."],"evidence_status":"Evidence recorded","metadata_completeness":40,"metadata_present":["Model category","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Organism","Anatomy","Cell type","Cell source","Culture system"],"dataset_context":"None recorded in same 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The donor was ascertained for sporadic ASD rather than as part of a White-Sutton syndrome cohort, so this is an informative human POGZ-neurodevelopmental-disorder model rather than a representative model of the full syndrome or its allelic spectrum.","notes":"The publication describes the donor as an ASD patient with a pathogenic POGZ variant; it does not establish that this single model captures the breadth of clinically diagnosed White-Sutton syndrome.","context_id":"disorder:White-Sutton_Syndrome","context_kind":"Disorder","disease_name":"White-Sutton Syndrome","disease_synonyms":["WHSUS","White-Sutton syndrome","POGZ-related intellectual disability syndrome","POGZ-related neurodevelopmental disorder"],"disease_term":{"id":"MONDO:0014606","label":"intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome","display_label":"White-Sutton 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cell","url":"http://purl.obolibrary.org/obo/CL_0011020"},{"id":"CL:0000540","label":"neuron","display_label":"neuron","url":"http://purl.obolibrary.org/obo/CL_0000540"}],"model_cell_type_labels":["neural progenitor cell","neuron"],"linked_cell_types":[{"id":"CL:0011020","label":"neural progenitor cell","display_label":"neural progenitor cell","url":"http://purl.obolibrary.org/obo/CL_0011020"},{"id":"CL:0010012","label":"cerebral cortex neuron","display_label":"cerebral cortex neuron","url":"http://purl.obolibrary.org/obo/CL_0010012"}],"linked_cell_type_labels":["neural progenitor cell","cerebral cortex neuron"],"cell_types":[{"id":"CL:0011020","label":"neural progenitor cell","display_label":"neural progenitor cell","url":"http://purl.obolibrary.org/obo/CL_0011020"},{"id":"CL:0000540","label":"neuron","display_label":"neuron","url":"http://purl.obolibrary.org/obo/CL_0000540"},{"id":"CL:0010012","label":"cerebral cortex neuron","display_label":"cerebral cortex neuron","url":"http://purl.obolibrary.org/obo/CL_0010012"}],"cell_type_labels":["neural progenitor cell","neuron","cerebral cortex neuron"],"conditions":["patient-derived POGZ p.Gln1042Arg cells","unaffected control-derived cells"],"cell_source":"Immortalized B cells from a person with sporadic ASD and de novo POGZ p.Gln1042Arg, and from an unaffected control, reprogrammed to iPSCs","source_category":"iPSC-derived","culture_system":"iPSC differentiation to neural stem cells, followed by early neuronal differentiation and radial-migration assays","publication":"PMID:32103003","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32103003","mechanisms":[{"target":"Impaired Cortical Neuronal Development","target_url":"https://dismech.monarchinitiative.org/pages/disorders/White-Sutton_Syndrome.html#pathophysiology-impaired-cortical-neuronal-development","relationship":"NOT_SPECIFIED","relationship_label":"Not Specified","fidelity":"NOT_SPECIFIED","fidelity_label":"Not Specified","description":"Models impaired neuronal differentiation and migration in human patient-derived neural cells.","limitations":null,"biological_scale":"CELLULAR","anatomy":[],"cell_types":[{"id":"CL:0011020","label":"neural progenitor cell","display_label":"neural progenitor cell","url":"http://purl.obolibrary.org/obo/CL_0011020"},{"id":"CL:0010012","label":"cerebral cortex neuron","display_label":"cerebral cortex neuron","url":"http://purl.obolibrary.org/obo/CL_0010012"}],"biological_processes":[{"id":"GO:0021895","label":"cerebral cortex neuron differentiation","display_label":"cerebral cortex neuron differentiation","url":"http://purl.obolibrary.org/obo/GO_0021895"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[],"evidence":[{"reference":"PMID:32103003","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/32103003","reference_title":"Pathogenic POGZ mutation causes impaired cortical development and reversible autism-like phenotypes.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The proportion of MAP2+ neurons was significantly lower in the patient-derived NSCs than in the control NSCs, suggesting that neuronal differentiation is impaired in the patient-derived NSCs","explanation":"Directly links the patient-derived neural model to impaired neuronal differentiation."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:White-Sutton_Syndrome","model_node_id":"model:kb/disorders/White-Sutton_Syndrome.yaml:Q1042R POGZ patient-derived iPSC neural model","focus_node_id":"node:disorder%3AWhite-Sutton_Syndrome:pathophysiology:Impaired%20Cortical%20Neuronal%20Development","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/White-Sutton_Syndrome.html#pathograph","nodes":[{"id":"model:kb/disorders/White-Sutton_Syndrome.yaml:Q1042R POGZ patient-derived iPSC neural 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The donor was ascertained for sporadic ASD rather than as part of a White-Sutton syndrome cohort, so this is an informative human POGZ-neurodevelopmental-disorder model rather than a representative model of the full syndrome or its allelic spectrum.","url":"https://dismech.monarchinitiative.org/pages/disorders/White-Sutton_Syndrome.html#experimental-model-q1042r-pogz-patient-derived-ipsc-neural-model","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AWhite-Sutton_Syndrome:pathophysiology:Impaired%20Cortical%20Neuronal%20Development","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Cortical Neuronal Development","description":"Disease-associated de novo POGZ variants impair neuronal development in the developing mouse brain and in induced pluripotent cell lines derived from a patient. The consequence in the mature animal is impaired cortical network function, which is the cellular substrate proposed for the cognitive and behavioural phenotype.","url":"https://dismech.monarchinitiative.org/pages/disorders/White-Sutton_Syndrome.html#pathophysiology-impaired-cortical-neuronal-development","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AWhite-Sutton_Syndrome:phenotype:Abnormal%20Brain%20Morphology","kind":"phenotype","kind_label":"Phenotype","label":"Abnormal Brain Morphology","description":"Abnormal brain morphology encompasses developmental malformations and other imaging abnormalities. Head imaging was abnormal in two-thirds of imaged individuals in one systematically surveyed cohort, with findings including nonspecific white matter changes, abnormal myelination, ventricular enlargement and volume loss; the epilepsy-focused literature adds cortical and cerebellar atrophy, delayed myelination and brainstem hypoplasia.","url":"https://dismech.monarchinitiative.org/pages/disorders/White-Sutton_Syndrome.html#phenotype-abnormal-brain-morphology","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AWhite-Sutton_Syndrome:phenotype:Behavioral%20Problems","kind":"phenotype","kind_label":"Phenotype","label":"Behavioral Problems","description":"Behavioural difficulties beyond autism are a consistent part of the phenotype. Aggressiveness and self-injury appear in the Orphanet-derived MONDO definition of the disorder; that is recorded here as background rather than cited as evidence, because no reference in this entry quantifies them.","url":"https://dismech.monarchinitiative.org/pages/disorders/White-Sutton_Syndrome.html#phenotype-behavioral-problems","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AWhite-Sutton_Syndrome:pathophysiology:Disrupted%20POGZ-Dependent%20Transcriptional%20Regulation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Disrupted POGZ-Dependent Transcriptional Regulation","description":"POGZ is a multidomain nuclear protein that binds chromatin and participates in transcriptional regulation. Loss of normal POGZ function therefore perturbs the transcriptional programs it controls in the developing nervous system, which is the proximate step linking the genetic lesion to abnormal cortical development.","url":"https://dismech.monarchinitiative.org/pages/disorders/White-Sutton_Syndrome.html#pathophysiology-disrupted-pogz-dependent-transcriptional-regulation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AWhite-Sutton_Syndrome:pathophysiology:Elevated%20Neuronal%20Excitability","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Elevated Neuronal Excitability","description":"In the heterozygous Pogz mouse, social deficits can be treated by compensatory inhibition of elevated cell excitability, identifying raised neuronal excitability as a functionally causal and pharmacologically reversible node rather than a fixed developmental endpoint. This is the single most therapeutically interesting finding in the disorder and is the reason a reversibility discussion is recorded. It is currently mouse-only.","url":"https://dismech.monarchinitiative.org/pages/disorders/White-Sutton_Syndrome.html#pathophysiology-elevated-neuronal-excitability","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3AWhite-Sutton_Syndrome:phenotype:Gait%20Abnormality","kind":"phenotype","kind_label":"Phenotype","label":"Gait Abnormality","description":"Gait abnormalities are a common problem in systematically assessed series.","url":"https://dismech.monarchinitiative.org/pages/disorders/White-Sutton_Syndrome.html#phenotype-gait-abnormality","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AWhite-Sutton_Syndrome:phenotype:Global%20Developmental%20Delay","kind":"phenotype","kind_label":"Phenotype","label":"Global Developmental Delay","description":"Developmental delay is near-universal and is disproportionately marked in speech and language acquisition.","url":"https://dismech.monarchinitiative.org/pages/disorders/White-Sutton_Syndrome.html#phenotype-global-developmental-delay","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AWhite-Sutton_Syndrome:phenotype:Hypotonia","kind":"phenotype","kind_label":"Phenotype","label":"Hypotonia","description":"Hypotonia is a commonly reported feature and contributes to the early motor delay.","url":"https://dismech.monarchinitiative.org/pages/disorders/White-Sutton_Syndrome.html#phenotype-hypotonia","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AWhite-Sutton_Syndrome:phenotype:Intellectual%20Disability","kind":"phenotype","kind_label":"Phenotype","label":"Intellectual Disability","description":"Cognitive impairment spans a wide range. In an unbiased national cohort of 19 individuals, 14 had frank intellectual disability (6 mild, 5 moderate, 3 severe) and the remaining 5 had learning disabilities with a shared neurocognitive profile of language difficulties, dysexecutive syndrome, attention disorders, slowness and social difficulties. Milder presentations are therefore likely to be under-ascertained.","url":"https://dismech.monarchinitiative.org/pages/disorders/White-Sutton_Syndrome.html#phenotype-intellectual-disability","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AWhite-Sutton_Syndrome:phenotype:Motor%20Delay","kind":"phenotype","kind_label":"Phenotype","label":"Motor Delay","description":"Motor development is delayed in most affected individuals; one systematically phenotyped series reported some degree of motor delay in 19 of 22 people.","url":"https://dismech.monarchinitiative.org/pages/disorders/White-Sutton_Syndrome.html#phenotype-motor-delay","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AWhite-Sutton_Syndrome:pathophysiology:Premature%20Cell-Cycle%20Exit%20in%20Cortical%20Progenitors","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Premature Cell-Cycle Exit in Cortical Progenitors","description":"In the embryonic (E15.5) cerebral cortex of Pogz-deficient mice the number of pHH3-positive mitotic cells is significantly reduced and the Tbr2-positive intermediate-progenitor layer is correspondingly expanded, while the Pax6-positive apical-progenitor layer is unchanged. 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Because feedback inhibition is the enzyme's sole regulatory brake and does not affect the ManNAc kinase activity, its loss leaves a constitutively active, rate-limiting enzyme even in the heterozygous state — the biochemical basis of the dominant inheritance.","url":"https://dismech.monarchinitiative.org/pages/disorders/Sialuria.html#pathophysiology-loss-of-cmp-neu5ac-feedback-inhibition-of-udp-glcnac-2-epimerase","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ASialuria:pathophysiology:GNE%20Allosteric-Site%20Missense%20Variant","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"GNE Allosteric-Site Missense Variant","description":"A single heterozygous missense variant in GNE at the allosteric CMP-Neu5Ac binding (feedback) site of the UDP-GlcNAc 2-epimerase domain. 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The resultant loss of feedback inhibition of GNE-epimerase activity by CMP-sialic acid causes excessive production of free sialic acid.","explanation":"States the causal chain from allosteric-site mutation through lost feedback to overproduction, which the rescue reverses."},{"reference":"PMID:18653764","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/18653764","reference_title":"Allele-specific silencing of the dominant disease allele in sialuria by RNA interference.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"mutant allele-specific silencing resulted in a significant decrease of free sialic acid, to within the normal range.","explanation":"Direct readout of reduced free sialic acid on mutant-allele knockdown."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Sialuria","model_node_id":"model:kb/disorders/Sialuria.yaml:R266Q sialuria patient fibroblasts with allele-specific siRNA silencing","focus_node_id":"node:disorder%3ASialuria:pathophysiology:Unregulated%20Overproduction%20of%20Free%20N-Acetylneuraminic%20Acid","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Sialuria.html#pathograph","nodes":[{"id":"model:kb/disorders/Sialuria.yaml:R266Q sialuria patient fibroblasts with allele-specific siRNA silencing","kind":"experimental_model","kind_label":"NAM model","label":"R266Q sialuria patient fibroblasts with allele-specific siRNA silencing","description":"Primary fibroblasts from an R266Q sialuria patient, used to test allele-specific knockdown. 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Because feedback inhibition is the enzyme's sole regulatory brake and does not affect the ManNAc kinase activity, its loss leaves a constitutively active, rate-limiting enzyme even in the heterozygous state — the biochemical basis of the dominant inheritance.","url":"https://dismech.monarchinitiative.org/pages/disorders/Sialuria.html#pathophysiology-loss-of-cmp-neu5ac-feedback-inhibition-of-udp-glcnac-2-epimerase","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ASialuria:pathophysiology:Massive%20Urinary%20Free%20Sialic%20Acid%20Excretion","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Massive Urinary Free Sialic Acid Excretion","description":"The overproduced free sialic acid is excreted in the urine in gram quantities (greater than 1 g/day), the biochemical hallmark of the disorder and the basis of its name. 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LARS2's editing domain is present but not functional, so the allele's effect is on aminoacylation.","context_id":"disorder:Hydrops-Lactic_Acidosis-Sideroblastic_Anemia-Multisystemic_Failure_Syndrome","context_kind":"Disorder","disease_name":"Hydrops-Lactic Acidosis-Sideroblastic Anemia-Multisystemic Failure Syndrome","disease_synonyms":["HLASA","hydrops, lactic acidosis, and sideroblastic anemia","hydrops, lactic acidosis, and sideroblastic anaemia","LARS2-related hydrops-lactic acidosis-sideroblastic anemia"],"disease_term":{"id":"MONDO:0014869","label":"hydrops-lactic acidosis-sideroblastic anemia-multisystemic failure syndrome","display_label":"hydrops-lactic acidosis-sideroblastic anemia-multisystemic failure syndrome","url":"http://purl.obolibrary.org/obo/MONDO_0014869"},"experimental_model_type":"OTHER","experimental_model_type_label":"Other","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":null,"source_category":null,"culture_system":null,"publication":null,"publication_url":null,"mechanisms":[{"target":"Reduced Leucyl-tRNA Aminoacylation","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Hydrops-Lactic_Acidosis-Sideroblastic_Anemia-Multisystemic_Failure_Syndrome.html#pathophysiology-reduced-leucyl-trna-aminoacylation","relationship":"MEASURES","relationship_label":"Measures","fidelity":"MODERATE","fidelity_label":"Moderate","description":"Quantifies the catalytic consequence of each allele: 18-fold and 9-fold losses of efficiency, driven by k-cat rather than K-m.","limitations":"The tRNA substrate is bacterial, not human mitochondrial tRNA-Leu, and the authors note that their wild-type kinetic values differ from previously published ones for exactly this reason — a different tRNA substrate was used. 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The assay also tests each variant enzyme alone, where the patient is compound heterozygous and carries both.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0006429","label":"leucyl-tRNA aminoacylation","display_label":"leucyl-tRNA aminoacylation","url":"http://purl.obolibrary.org/obo/GO_0006429"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Catalytic efficiency of leucylation","description":null,"target":"Reduced Leucyl-tRNA Aminoacylation","direction":"DECREASED","interpretation":"Both patient alleles retain measurable activity, which is the observation that makes this a hypomorphic rather than a null genotype.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:26537577","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/26537577","reference_title":"LARS2 Variants Associated with Hydrops, Lactic Acidosis, Sideroblastic Anemia, and Multisystem Failure.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"LARS2 p.Ala430Val demonstrated an 18-fold loss of catalytic efficiency and LARS2 p.Thr522Asn showed a 9-fold reduction compared to WT LARS2, essentially due to decreased catalytic rates","explanation":"The two fold-changes and the kinetic parameter they come from, which is what distinguishes a slow enzyme from one that cannot find its substrate."}],"notes":null}],"evidence":[{"reference":"PMID:26537577","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/26537577","reference_title":"LARS2 Variants Associated with Hydrops, Lactic Acidosis, Sideroblastic Anemia, and Multisystem Failure.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Kinetic parameters were determined from Lineweaver–Burk plots in the presence of 3–30 nM WT or variant LARS2 and concentrations of E. coli tRNALeu transcript ranging from 0.3 to 5.6 μM.","explanation":"The assay design, quoted so a reader can see what the model does and does not contain."},{"reference":"PMID:26537577","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/26537577","reference_title":"LARS2 Variants Associated with Hydrops, Lactic Acidosis, Sideroblastic Anemia, and Multisystem Failure.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"LARS2 p.Ala430Val demonstrated an 18-fold loss of catalytic efficiency and LARS2 p.Thr522Asn showed a 9-fold reduction compared to WT LARS2, essentially due to decreased catalytic rates","explanation":"The two fold-changes and the kinetic parameter they come from, which is what distinguishes a slow enzyme from one that cannot find its substrate."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Hydrops-Lactic_Acidosis-Sideroblastic_Anemia-Multisystemic_Failure_Syndrome","model_node_id":"model:kb/disorders/Hydrops-Lactic_Acidosis-Sideroblastic_Anemia-Multisystemic_Failure_Syndrome.yaml:Recombinant LARS2 aminoacylation assay","focus_node_id":"node:disorder%3AHydrops-Lactic_Acidosis-Sideroblastic_Anemia-Multisystemic_Failure_Syndrome:pathophysiology:Reduced%20Leucyl-tRNA%20Aminoacylation","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Hydrops-Lactic_Acidosis-Sideroblastic_Anemia-Multisystemic_Failure_Syndrome.html#pathograph","nodes":[{"id":"model:kb/disorders/Hydrops-Lactic_Acidosis-Sideroblastic_Anemia-Multisystemic_Failure_Syndrome.yaml:Recombinant LARS2 aminoacylation assay","kind":"experimental_model","kind_label":"NAM model","label":"Recombinant LARS2 aminoacylation assay","description":"Purified recombinant human LARS2, wild-type and each patient variant, assayed for leucylation of an E. coli tRNA-Leu transcript with carbon-14 leucine, with kinetic parameters from Lineweaver-Burk plots. Deacylation and misacylation controls were run in the same system.\nThis is the only functional model of the disease that exists, and it is a purified-enzyme assay rather than a cell or animal model.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hydrops-Lactic_Acidosis-Sideroblastic_Anemia-Multisystemic_Failure_Syndrome.html#experimental-model-recombinant-lars2-aminoacylation-assay","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHydrops-Lactic_Acidosis-Sideroblastic_Anemia-Multisystemic_Failure_Syndrome:pathophysiology:Reduced%20Leucyl-tRNA%20Aminoacylation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced Leucyl-tRNA Aminoacylation","description":"Less charged mitochondrial tRNA-Leu is available to the mitoribosome. The kinetics show the loss is in catalytic rate rather than in substrate affinity: k-cat falls roughly fourteen-fold for p.Ala430Val and ninefold for p.Thr522Asn while K-m barely moves. An enzyme that binds its substrate normally and turns it over slowly is a hypomorph whose output scales with how much of it there is, which is the basis for expecting tissue-dependent severity.\nAcross the 2020 series the HLASA alleles were the most severely impaired of all LARS2 variants assayed, which extends the relationship from one family to the spectrum.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hydrops-Lactic_Acidosis-Sideroblastic_Anemia-Multisystemic_Failure_Syndrome.html#pathophysiology-reduced-leucyl-trna-aminoacylation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3AHydrops-Lactic_Acidosis-Sideroblastic_Anemia-Multisystemic_Failure_Syndrome:pathophysiology:Biallelic%20Hypomorphic%20LARS2%20Variants","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Biallelic Hypomorphic LARS2 Variants","description":"The index proband carries c.1289C>T, p.Ala430Val in trans with c.1565C>A, p.Thr522Asn. The second allele is the same one reported homozygously in Perrault syndrome, which is the single most informative fact about this entity: the severe and the mild phenotype share an allele, so severity is a property of the allele combination rather than of the variant.\nThe two residues sit in different parts of the enzyme. Thr522 is in the catalytic domain where the 3-prime end of the tRNA binds, and Ala430 is in the CP1 connective-peptide domain, which in cytosolic synthetases is an editing domain. LARS2's editing domain is present but not functional, and the authors tested that directly — no mischarging with isoleucine was detectable for wild-type or variant enzyme. So the Ala430Val effect is on aminoacylation rather than on proofreading, which is worth recording because the domain's name invites the opposite inference.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hydrops-Lactic_Acidosis-Sideroblastic_Anemia-Multisystemic_Failure_Syndrome.html#pathophysiology-biallelic-hypomorphic-lars2-variants","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3AHydrops-Lactic_Acidosis-Sideroblastic_Anemia-Multisystemic_Failure_Syndrome:pathophysiology:Impaired%20Mitochondrial%20Translation%20in%20High-Demand%20Tissues","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Mitochondrial Translation in High-Demand Tissues","description":"Translation of the thirteen mtDNA-encoded respiratory-chain subunits depends on a supply of charged tRNA-Leu, and a hypomorphic synthetase restricts it. The tissue qualifier is not decoration: in the index proband's fibroblasts and induced myotubes, LARS2 protein was normal, respiratory-chain proteins were normal, and an in vitro mitochondrial protein synthesis assay found no defect at all. The authors conclude the variants affect only tissues with higher energy demands.\nGraded PROVISIONAL because the translation defect itself was never demonstrated in an affected tissue. What was demonstrated in liver and muscle is reduced LARS2 protein and reduced complex I protein; the translation step between them is inferred from the enzyme's known function. The one assay that could have shown it was run in the tissue where the disease is absent.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hydrops-Lactic_Acidosis-Sideroblastic_Anemia-Multisystemic_Failure_Syndrome.html#pathophysiology-impaired-mitochondrial-translation-in-high-demand-tissues","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"}],"edges":[{"id":"model-link:0:model:kb/disorders/Hydrops-Lactic_Acidosis-Sideroblastic_Anemia-Multisystemic_Failure_Syndrome.yaml:Recombinant LARS2 aminoacylation assay","source_id":"model:kb/disorders/Hydrops-Lactic_Acidosis-Sideroblastic_Anemia-Multisystemic_Failure_Syndrome.yaml:Recombinant LARS2 aminoacylation 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Engineered interface substitutions can impair complex formation; this does not directly establish the effect of each patient allele.","notes":null,"context_id":"disorder:Bone_Fragility_With_Contractures_Arterial_Rupture_And_Deafness","context_kind":"Disorder","disease_name":"Bone Fragility With Contractures Arterial Rupture And Deafness","disease_synonyms":["BCARD syndrome","lysyl hydroxylase 3 deficiency","LH3 deficiency","PLOD3-related connective tissue disorder"],"disease_term":{"id":"MONDO:0012892","label":"bone fragility with contractures, arterial rupture, and deafness","display_label":"bone fragility with contractures, arterial rupture, and deafness","url":"http://purl.obolibrary.org/obo/MONDO_0012892"},"experimental_model_type":"OTHER","experimental_model_type_label":"Other","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"Homo sapiens","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},"organism_label":"Homo sapiens","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":null,"source_category":null,"culture_system":null,"publication":"PMID:40069201","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40069201","mechanisms":[{"target":"Reduced Collagen Hydroxylysine Glucosylation","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Bone_Fragility_With_Contractures_Arterial_Rupture_And_Deafness.html#pathophysiology-reduced-collagen-hydroxylysine-glucosylation","relationship":"MEASURES","relationship_label":"Measures","fidelity":"NOT_SPECIFIED","fidelity_label":"Not Specified","description":null,"limitations":"Wild-type and engineered recombinant systems define the normal machinery; variant-specific effects require direct testing.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0180062","label":"protein O-linked glycosylation via galactose","display_label":"Hydroxylysine-linked collagen glycosylation","url":"http://purl.obolibrary.org/obo/GO_0180062"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[],"evidence":[{"reference":"PMID:40069201","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40069201","reference_title":"The structural basis for the human procollagen lysine hydroxylation and dual-glycosylation.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The structures reveal a stoichiometry of 2:2 between the two enzymes in the LH3-ColGalT1 quaternary complex","explanation":"Cryo-EM and recombinant complex assays support coordinated modification by distinct enzymes."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Bone_Fragility_With_Contractures_Arterial_Rupture_And_Deafness","model_node_id":"model:kb/disorders/Bone_Fragility_With_Contractures_Arterial_Rupture_And_Deafness.yaml:Recombinant LH3-COLGALT1 Complex","focus_node_id":"node:disorder%3ABone_Fragility_With_Contractures_Arterial_Rupture_And_Deafness:pathophysiology:Reduced%20Collagen%20Hydroxylysine%20Glucosylation","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Bone_Fragility_With_Contractures_Arterial_Rupture_And_Deafness.html#pathograph","nodes":[{"id":"model:kb/disorders/Bone_Fragility_With_Contractures_Arterial_Rupture_And_Deafness.yaml:Recombinant LH3-COLGALT1 Complex","kind":"experimental_model","kind_label":"NAM model","label":"Recombinant LH3-COLGALT1 Complex","description":"Purified recombinant proteins, cryo-EM and enzymatic assays define a 2:2 LH3-COLGALT1 complex and separate hydroxylase, galactosyltransferase and glucosyltransferase functions. 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These enzymes form a 2:2 complex. Abnormal collagen glycosylation is supported by patient urinary products and by collagen analyses in knockout cells; it is not equivalent to loss of every sugar from every collagen. The process term includes elongation of a galactose-linked glycan; it does not assign the preceding galactose-transfer reaction to LH3.","url":"https://dismech.monarchinitiative.org/pages/disorders/Bone_Fragility_With_Contractures_Arterial_Rupture_And_Deafness.html#pathophysiology-reduced-collagen-hydroxylysine-glucosylation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ABone_Fragility_With_Contractures_Arterial_Rupture_And_Deafness:pathophysiology:Abnormal%20Type%20IV%20Collagen%20Triple%20Helix","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Abnormal Type IV Collagen Triple Helix","description":"Type IV collagen isolated from LH3-knockout PFHR9 cells lacked a stable normal triple helix, showed altered HSP47 binding and failed to form normal higher-order assemblies. HSP47 binding was reduced or altered, rather than absent.","url":"https://dismech.monarchinitiative.org/pages/disorders/Bone_Fragility_With_Contractures_Arterial_Rupture_And_Deafness.html#pathophysiology-abnormal-type-iv-collagen-triple-helix","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ABone_Fragility_With_Contractures_Arterial_Rupture_And_Deafness:pathophysiology:Altered%20Extracellular%20Collagen%20Fibril%20Organization","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Altered Extracellular Collagen Fibril Organization","description":"Selective hydroxylase-deficient mice show disorganized fibrils, and mutant zebrafish cartilage has sparse extracellular collagen fibrils. These findings support a matrix-organization defect, while the contribution of individual collagen substrates to human bone fragility remains unresolved.","url":"https://dismech.monarchinitiative.org/pages/disorders/Bone_Fragility_With_Contractures_Arterial_Rupture_And_Deafness.html#pathophysiology-altered-extracellular-collagen-fibril-organization","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ABone_Fragility_With_Contractures_Arterial_Rupture_And_Deafness:pathophysiology:Impaired%20Type%20VI%20Collagen%20Tetramerization","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Type VI Collagen Tetramerization","description":"In LH3-null embryos and cultured cells, deficient hydroxylysine glycosylation impairs intracellular type VI collagen tetramerization. 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The energy cost of contraction rises and diastolic filling is impaired, the proximate driver of the hypertrophic response.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_7.html#pathophysiology-myofilament-calcium-hypersensitization-and-impaired-relaxation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Hypertrophic_Cardiomyopathy_7.yaml:Reconstituted human cardiac thin filament with mutant troponin I","source_id":"model:kb/disorders/Hypertrophic_Cardiomyopathy_7.yaml:Reconstituted human cardiac thin filament with mutant troponin 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cardiac muscle","url":"http://purl.obolibrary.org/obo/GO_0055119"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[],"evidence":[],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Hypertrophic_Cardiomyopathy_7","model_node_id":"model:kb/disorders/Hypertrophic_Cardiomyopathy_7.yaml:Reconstituted human cardiac thin filament with mutant troponin I","focus_node_id":"node:disorder%3AHypertrophic_Cardiomyopathy_7:pathophysiology:Myofilament%20Calcium%20Hypersensitization%20and%20Impaired%20Relaxation","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_7.html#pathograph","nodes":[{"id":"model:kb/disorders/Hypertrophic_Cardiomyopathy_7.yaml:Reconstituted human cardiac thin filament with mutant troponin I","kind":"experimental_model","kind_label":"NAM model","label":"Reconstituted human cardiac thin filament with mutant troponin I","description":"Biochemical reconstitution comparing wild-type human troponin complex with the HCM-associated K206I cardiac troponin I variant in a regulated actomyosin system, plus troponin exchange into detergent-extracted cardiac fibers for force measurement. Isolates the effect of the variant on calcium sensitivity and on the inhibitory function of troponin I independent of remodeling.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_7.html#experimental-model-reconstituted-human-cardiac-thin-filament-with-mutant-troponin-i","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_7:pathophysiology:Myofilament%20Calcium%20Hypersensitization%20and%20Impaired%20Relaxation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Myofilament Calcium Hypersensitization and Impaired Relaxation","description":"Loss of troponin I inhibition shifts the force-calcium relationship leftward: the thin filament activates at lower calcium concentrations, cross-bridges are recruited inappropriately during diastole, and relaxation is slowed. In human hypertrophic cardiomyopathy myocardium this hypersensitivity is accompanied by hypophosphorylation of protein kinase A targets and by blunted length-dependent activation — the myofilament basis of the Frank-Starling response — and in TNNI3-mutant samples replacing the mutant troponin with wild-type protein restores length-dependent activation, establishing the troponin lesion as causal rather than secondary. The energy cost of contraction rises and diastolic filling is impaired, the proximate driver of the hypertrophic response.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_7.html#pathophysiology-myofilament-calcium-hypersensitization-and-impaired-relaxation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_7:pathophysiology:Cardiac%20Troponin%20I%20Inhibitory%20Dysfunction","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Cardiac Troponin I Inhibitory Dysfunction","description":"TNNI3 encodes cardiac troponin I, the inhibitory subunit of the cardiac troponin complex on the thin filament. In diastole it anchors actin-tropomyosin in the blocked state; on systolic calcium binding to troponin C the inhibitory and switch peptides release actin, permitting cross-bridge cycling. CMH7-associated variants are predominantly heterozygous missense changes distributed across the N-terminal PKA-phosphorylation extension, the troponin T/troponin C binding region, the inhibitory peptide, and the C-terminal actin-binding region. They do not abolish the protein; they degrade its inhibitory capacity and its interactions with troponin C and troponin T, which is the primary lesion of this disorder. The distribution is not uniform across the gene: approximately 80% of reported pathogenic TNNI3 variants fall in exons 7 and 8, which encode the actin- and troponin-C-interacting domains - so the mutational hotspot coincides with the functional interfaces this node describes, which is why variant position carries interpretive weight in this gene.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_7.html#pathophysiology-cardiac-troponin-i-inhibitory-dysfunction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_7:pathophysiology:Cardiomyocyte%20Hypertrophy%2C%20Myocyte%20Disarray%20and%20Interstitial%20Fibrosis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Cardiomyocyte Hypertrophy, Myocyte Disarray and Interstitial Fibrosis","description":"The remodeling myocardium of hypertrophic cardiomyopathy is defined histologically by three co-occurring features: cardiomyocyte hypertrophy, myocyte and myofibrillar disarray, and interstitial fibrosis from activated cardiac fibroblasts depositing excess collagen. In TNNI3 disease this triad is reproduced in the cTnI-G203S transgenic mouse and is seen in autopsy myocardium from carriers of the malignant p.Arg21Cys founder allele. The fibrotic and disarrayed myocardium is both the substrate of diastolic stiffening and the electrical substrate for re-entrant arrhythmia; in surgical series the degree of disarray and fibrosis tracks with defibrillator implantation and atrial fibrillation.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_7.html#pathophysiology-cardiomyocyte-hypertrophy-myocyte-disarray-and-interstitial-fibrosis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AHypertrophic_Cardiomyopathy_7:pathophysiology:Left%20Ventricular%20Hypertrophy%20with%20Diastolic%20Dysfunction","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Left Ventricular Hypertrophy with Diastolic Dysfunction","description":"The organ-level result is a thickened, stiff, hypercontractile left ventricle with a small cavity and impaired filling. Diastolic dysfunction rather than reduced ejection fraction dominates the physiology, and dynamic left ventricular outflow tract obstruction develops when a hypertrophied septum and systolic anterior motion of the mitral valve narrow the outflow tract during systole. In thin-filament genotypes such as TNNI3 the maximal wall thickness is on average lower than in thick-filament disease, so the diagnosis can be missed if wall thickness alone is used, while progression to advanced heart failure may be faster.","url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_7.html#pathophysiology-left-ventricular-hypertrophy-with-diastolic-dysfunction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:1:model:kb/disorders/Hypertrophic_Cardiomyopathy_7.yaml:Reconstituted human cardiac thin filament with mutant troponin I","source_id":"model:kb/disorders/Hypertrophic_Cardiomyopathy_7.yaml:Reconstituted human cardiac thin filament with mutant troponin 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Troponin I Inhibitory Dysfunction","Myofilament Calcium Hypersensitization and Impaired Relaxation"],"relationships":["Not Specified"],"fidelities":["Not Specified"],"biological_scales":["Molecular"],"system_context_sources":["Linked mechanism anatomy","Linked mechanism cell type","Linked mechanism biological scale"],"modeled_system_labels":["myocardium","cardiac muscle cell","Molecular"],"biological_process_terms":[{"id":"GO:0055117","label":"regulation of cardiac muscle contraction","display_label":"Regulation of cardiac muscle contraction","url":"http://purl.obolibrary.org/obo/GO_0055117"},{"id":"GO:0045214","label":"sarcomere organization","display_label":"Sarcomere organization","url":"http://purl.obolibrary.org/obo/GO_0045214"},{"id":"GO:0086004","label":"regulation of cardiac muscle cell contraction","display_label":"Regulation of cardiac muscle cell contraction","url":"http://purl.obolibrary.org/obo/GO_0086004"},{"id":"GO:0055119","label":"relaxation of cardiac muscle","display_label":"Relaxation of cardiac muscle","url":"http://purl.obolibrary.org/obo/GO_0055119"}],"biological_processes":["regulation of cardiac muscle contraction","sarcomere organization","regulation of cardiac muscle cell contraction","relaxation of cardiac muscle"],"pathway_terms":[],"pathways":[],"gene_terms":[{"id":"hgnc:11947","label":"TNNI3","display_label":"TNNI3","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/11947"}],"genes":["TNNI3"],"chemical_terms":[],"chemicals":[],"readout_names":[],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:26553696","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/26553696","reference_title":"Green Tea Catechin Normalizes the Enhanced Ca2+ Sensitivity of Myofilaments Regulated by a Hypertrophic Cardiomyopathy-Associated Mutation in Human Cardiac Troponin I (K206I).","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"To determine molecular mechanism(s) of the mutant human cardiac troponin I (K206I), we tested the Ca(2+) dependence of thin filament-activated myosin-S1-ATPase activity in a reconstituted, regulated, actomyosin system","explanation":"Describes the reconstituted system and its readout as applied to an HCM-associated TNNI3 variant."}],"evidence_text":["To determine molecular mechanism(s) of the mutant human cardiac troponin I (K206I), we tested the Ca(2+) dependence of thin filament-activated myosin-S1-ATPase activity in a reconstituted, regulated, actomyosin system","Describes the reconstituted system and its readout as applied to an HCM-associated TNNI3 variant."],"evidence_status":"Evidence recorded","metadata_completeness":70,"metadata_present":["Model category","Organism","Anatomy","Cell type","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Cell source","Culture system"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Hypertrophic_Cardiomyopathy_7.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hypertrophic_Cardiomyopathy_7.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_7.html#experimental-model-reconstituted-human-cardiac-thin-filament-with-mutant-troponin-i","source_anchor":"experimental-model-reconstituted-human-cardiac-thin-filament-with-mutant-troponin-i"},{"id":"model:kb/disorders/VAMP2-Related_Disorder.yaml:Reconstituted SNARE liposome lipid-mixing (fusion) assay","name":"Reconstituted SNARE liposome lipid-mixing (fusion) assay","description":"Cell-free reconstitution in which purified wild-type or variant VAMP2 is incorporated into fluorescent donor liposomes and the syntaxin-1/SNAP-25 t-SNARE complex into acceptor liposomes; fusion is read out as NBD-to-rhodamine dequenching. Run with and without Munc18-1, and with 50:50 wild-type:mutant donor liposomes to emulate the heterozygous state. This is the assay behind the entry's fusion claims, and behind their variant-specific limits.","notes":null,"context_id":"disorder:VAMP2-Related_Disorder","context_kind":"Disorder","disease_name":"VAMP2-Related Neurodevelopmental Disorder","disease_synonyms":[],"disease_term":{"id":"MONDO:0032900","label":"neurodevelopmental disorder with hypotonia and autistic features with or without hyperkinetic movements","display_label":"VAMP2-related neurodevelopmental disorder with hypotonia and autistic features","url":"http://purl.obolibrary.org/obo/MONDO_0032900"},"experimental_model_type":"OTHER","experimental_model_type_label":"Other","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[{"id":"CL:0000540","label":"neuron","display_label":"neuron","url":"http://purl.obolibrary.org/obo/CL_0000540"}],"linked_cell_type_labels":["neuron"],"cell_types":[{"id":"CL:0000540","label":"neuron","display_label":"neuron","url":"http://purl.obolibrary.org/obo/CL_0000540"}],"cell_type_labels":["neuron"],"conditions":[],"cell_source":null,"source_category":null,"culture_system":null,"publication":"PMID:30929742","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/30929742","mechanisms":[{"target":"Impaired SNARE-Mediated Vesicle Fusion","target_url":"https://dismech.monarchinitiative.org/pages/disorders/VAMP2-Related_Neurodevelopmental_Disorder.html#pathophysiology-impaired-snare-mediated-vesicle-fusion","relationship":"MEASURES","relationship_label":"Measures","fidelity":"MODERATE","fidelity_label":"Moderate","description":"Isolates the SNARE fusion step from all other presynaptic biology, which is what makes it decisive for p.Ser75Pro and uninformative for variants whose defect lies in regulatory-protein interaction.","limitations":"Contains only the core SNAREs (plus Munc18-1 where added) — synaptotagmin-1, complexin, and Munc13 are absent, so a variant that acts through those regulators scores as normal. p.Glu78Ala is the worked example: pathogenic in patients, indistinguishable from wild-type here. p.Phe77Ser could not be purified and was never tested.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[{"id":"CL:0000540","label":"neuron","display_label":"neuron","url":"http://purl.obolibrary.org/obo/CL_0000540"}],"biological_processes":[{"id":"GO:0099502","label":"calcium-dependent activation of synaptic vesicle fusion","display_label":"calcium-dependent activation of synaptic vesicle fusion","url":"http://purl.obolibrary.org/obo/GO_0099502"},{"id":"GO:0016079","label":"synaptic vesicle exocytosis","display_label":"synaptic vesicle exocytosis","url":"http://purl.obolibrary.org/obo/GO_0016079"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Endpoint liposome fusion normalized to wild-type VAMP2","description":null,"target":"Impaired SNARE-Mediated Vesicle Fusion","direction":"DECREASED","interpretation":"Fell to ~25% of wild-type for p.Ser75Pro; unchanged for p.Glu78Ala.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:30929742","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30929742","reference_title":"Mutations in the Neuronal Vesicular SNARE VAMP2 Affect Synaptic Membrane Fusion and Impair Human Neurodevelopment.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"the VAMP2 disease-associated variant p.Ser75Pro reduced the rate and extent of fusion compared to that seen with VAMP2 WT, whereas the p.Glu78Ala variant had little to no effect","explanation":"The primary readout, reported for both variants, including the negative result."}],"notes":null}],"evidence":[{"reference":"PMID:30929742","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30929742","reference_title":"Mutations in the Neuronal Vesicular SNARE VAMP2 Affect Synaptic Membrane Fusion and Impair Human Neurodevelopment.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"To evaluate the functional consequence of VAMP2 variants, we employed the reconstituted, lipid-mixing assay based on NBD","explanation":"Establishes the assay as the functional test applied to the disease variants."},{"reference":"PMID:30929742","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30929742","reference_title":"Mutations in the Neuronal Vesicular SNARE VAMP2 Affect Synaptic Membrane Fusion and Impair Human Neurodevelopment.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"the VAMP2 disease-associated variant p.Ser75Pro reduced the rate and extent of fusion compared to that seen with VAMP2 WT, whereas the p.Glu78Ala variant had little to no effect","explanation":"The primary readout, reported for both variants, including the negative result."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:VAMP2-Related_Disorder","model_node_id":"model:kb/disorders/VAMP2-Related_Disorder.yaml:Reconstituted SNARE liposome lipid-mixing (fusion) assay","focus_node_id":"node:disorder%3AVAMP2-Related_Disorder:pathophysiology:Impaired%20SNARE-Mediated%20Vesicle%20Fusion","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/VAMP2-Related_Neurodevelopmental_Disorder.html#pathograph","nodes":[{"id":"model:kb/disorders/VAMP2-Related_Disorder.yaml:Reconstituted SNARE liposome lipid-mixing (fusion) assay","kind":"experimental_model","kind_label":"NAM model","label":"Reconstituted SNARE liposome lipid-mixing (fusion) assay","description":"Cell-free reconstitution in which purified wild-type or variant VAMP2 is incorporated into fluorescent donor liposomes and the syntaxin-1/SNAP-25 t-SNARE complex into acceptor liposomes; fusion is read out as NBD-to-rhodamine dequenching. Run with and without Munc18-1, and with 50:50 wild-type:mutant donor liposomes to emulate the heterozygous state. This is the assay behind the entry's fusion claims, and behind their variant-specific limits.","url":"https://dismech.monarchinitiative.org/pages/disorders/VAMP2-Related_Neurodevelopmental_Disorder.html#experimental-model-reconstituted-snare-liposome-lipid-mixing-fusion-assay","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AVAMP2-Related_Disorder:pathophysiology:Impaired%20SNARE-Mediated%20Vesicle%20Fusion","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired SNARE-Mediated Vesicle Fusion","description":"VAMP2 is one of the three core neuronal SNAREs whose zippering, triggered by the calcium sensor synaptotagmin-1, fuses the synaptic vesicle with the presynaptic membrane. The fusion defect is variant-specific rather than uniform across the allelic series: in the reconstituted lipid-mixing assay p.Ser75Pro reduced fusion to roughly 25% of wild-type and could not be activated by Munc18-1 (a >90% loss-of-function under Munc18-activated conditions), whereas p.Glu78Ala was indistinguishable from wild-type and p.Phe77Ser could not be purified for testing. In cultured neurons, two of three variants tested reduced both the rate of exocytosis and the size of the released recycling pool. The authors therefore frame impaired fusion as one of the possible mechanisms and explicitly invoke mutation-specific mechanisms; for variants without a reconstituted fusion defect, disrupted interaction with regulatory proteins absent from the assay is the proposed alternative. This is the module's key conformance target — the fusion-machinery arm.","url":"https://dismech.monarchinitiative.org/pages/disorders/VAMP2-Related_Neurodevelopmental_Disorder.html#pathophysiology-impaired-snare-mediated-vesicle-fusion","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AVAMP2-Related_Disorder:pathophysiology:Disrupted%20Neurotransmission%20and%20Impaired%20Neurodevelopment","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Disrupted Neurotransmission and Impaired Neurodevelopment","description":"Impaired SNARE-mediated fusion reduces activity-dependent neurotransmitter release, disturbing cortical synaptic transmission and activity-dependent brain development. This produces axial hypotonia from birth, intellectual disability, and autistic features with motor stereotypies. Within the index cohort the three C-terminal missense carriers were additionally the ones with central visual impairment and a hyperkinetic movement disorder, but neither is curated as holding across all reported patients: a p.Ala67Pro carrier developed a hyperkinetic movement disorder, and for central visual impairment it is the preceding poor visual fixation that is documented outside the cluster. Seizures occur across allelic classes and are likewise not curated as a genotype-specific consequence.","url":"https://dismech.monarchinitiative.org/pages/disorders/VAMP2-Related_Neurodevelopmental_Disorder.html#pathophysiology-disrupted-neurotransmission-and-impaired-neurodevelopment","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AVAMP2-Related_Disorder:pathophysiology:Dominant-Negative%20Interference%20with%20Wild-Type%20VAMP2","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Dominant-Negative Interference with Wild-Type VAMP2","description":"SNARE-motif missense variants produce a protein that is still incorporated into the SNARE complex but assembles or zippers defectively, so the mutant poisons complexes that also contain wild-type VAMP2. 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Two caveats keep this arm weaker than the dominant-negative one: nonsense-mediated decay is predicted rather than measured, and the authors attribute the absent dominant-negative effect possibly to their construct lacking the transmembrane domain, noting it was not directly tested.","url":"https://dismech.monarchinitiative.org/pages/disorders/VAMP2-Related_Neurodevelopmental_Disorder.html#pathophysiology-vamp2-haploinsufficiency","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/VAMP2-Related_Disorder.yaml:Reconstituted SNARE liposome lipid-mixing (fusion) assay","source_id":"model:kb/disorders/VAMP2-Related_Disorder.yaml:Reconstituted SNARE liposome lipid-mixing (fusion) 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no isogenic correction isolates the causal mediator.","A 24-hour scratch assay measures reduced wound closure in the patient-derived cultures; it does not measure migration into human pharyngeal arches."],"evidence_status":"Evidence recorded","metadata_completeness":60,"metadata_present":["Model category","Cell type","Cell source","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Organism","Anatomy","Culture system"],"dataset_context":"Available in same entry","context_dataset_ids":["dataset:dbgap:phs000437"],"candidate_dataset_ids":[],"source_path":"kb/disorders/Auriculocondylar_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Auriculocondylar_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Auriculocondylar_Syndrome.html#experimental-model-regulatory-duplication-patient-ipsc-neural-crest-cultures","source_anchor":"experimental-model-regulatory-duplication-patient-ipsc-neural-crest-cultures"},{"id":"model:kb/disorders/Neurodevelopmental_Disorder_with_or_without_Anomalies_of_the_Brain_Eye_or_Heart.yaml:ReMut CRISPR/Cas9 RERE frameshift knock-in cell line","name":"ReMut CRISPR/Cas9 RERE frameshift knock-in cell line","description":"A cell line carrying the patient's RERE frameshift variant (c.3732delC, p.Tyr1245Thrfs*12), generated by CRISPR/Cas9 genome editing and profiled by RNA sequencing and mass spectrometry. 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It also carries one frameshift allele, so it speaks only to the loss-of-function class. No independent replication of these omics findings has been reported.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0007224","label":"smoothened signaling pathway","display_label":"smoothened signaling pathway","url":"http://purl.obolibrary.org/obo/GO_0007224"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"HDAC1 and HDAC2 abundance","description":null,"target":"Deregulated Developmental Morphogen Signaling","direction":"ALTERED","interpretation":"Perturbation of the two histone deacetylase subunits of the WHHERE complex, the complex through which RERE regulates retinoic acid targets.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:38018232","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38018232","reference_title":"A de novo variant in RERE causes autistic behavior by disrupting related genes and signaling pathway.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"we noted alterations in HDAC1 and HDAC2, which are members of the WHHERE complex, suggesting their role in the pathogenesis of this patient","explanation":"The measured change in WHHERE complex components grounding this readout."}],"notes":null}],"evidence":[{"reference":"PMID:38018232","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38018232","reference_title":"A de novo variant in RERE causes autistic behavior by disrupting related genes and signaling pathway.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We identified 3790 differentially expressed genes and 684 differentially expressed proteins.","explanation":"Establishes that the line yields genome-wide molecular readouts. Marked PARTIAL because a differential-expression count supports that the model measures something, not that it faithfully represents the human mechanism — hence the LOW fidelity."},{"reference":"PMID:38018232","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38018232","reference_title":"A de novo variant in RERE causes autistic behavior by disrupting related genes and signaling pathway.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"we noted alterations in HDAC1 and HDAC2, which are members of the WHHERE complex, suggesting their role in the pathogenesis of this patient","explanation":"The measured change in WHHERE complex components grounding this readout."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Neurodevelopmental_Disorder_with_or_without_Anomalies_of_the_Brain_Eye_or_Heart","model_node_id":"model:kb/disorders/Neurodevelopmental_Disorder_with_or_without_Anomalies_of_the_Brain_Eye_or_Heart.yaml:ReMut CRISPR/Cas9 RERE frameshift knock-in cell line","focus_node_id":"node:disorder%3ANeurodevelopmental_Disorder_with_or_without_Anomalies_of_the_Brain_Eye_or_Heart:pathophysiology:Deregulated%20Developmental%20Morphogen%20Signaling","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Neurodevelopmental_Disorder_with_or_without_Anomalies_of_the_Brain,_Eye,_or_Heart.html#pathograph","nodes":[{"id":"model:kb/disorders/Neurodevelopmental_Disorder_with_or_without_Anomalies_of_the_Brain_Eye_or_Heart.yaml:ReMut CRISPR/Cas9 RERE frameshift knock-in cell line","kind":"experimental_model","kind_label":"NAM model","label":"ReMut CRISPR/Cas9 RERE frameshift knock-in cell line","description":"A cell line carrying the patient's RERE frameshift variant (c.3732delC, p.Tyr1245Thrfs*12), generated by CRISPR/Cas9 genome editing and profiled by RNA sequencing and mass spectrometry. The line showed 3,790 differentially expressed genes and 684 differentially expressed proteins, with SHH signaling downregulated and Hippo signaling upregulated, plus altered HDAC1 and HDAC2 — the two histone deacetylase members of the WHHERE complex through which RERE acts. It is the only patient-variant-matched cellular model in this entry.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Neurodevelopmental_Disorder_with_or_without_Anomalies_of_the_Brain,_Eye,_or_Heart.html#experimental-model-remut-crispr-cas9-rere-frameshift-knock-in-cell-line","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ANeurodevelopmental_Disorder_with_or_without_Anomalies_of_the_Brain_Eye_or_Heart:pathophysiology:Deregulated%20Developmental%20Morphogen%20Signaling","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Deregulated Developmental Morphogen Signaling","description":"RERE normally restrains sonic hedgehog (shh) and fgf8 signaling during patterning. NEDBEH-associated human RERE variants behave as hypomorphs in their ability to repress shh signaling, and some show abnormal nuclear localization. In the zebrafish rerea mutant this manifests as expanded fgf8 and pax2a expression domains in the optic stalk with reduced vax1, and in a patient-derived CRISPR knock-in cell line as downregulated SHH signaling with reciprocal upregulation of the Hippo pathway. The direction of the shh change differs between these systems, which is recorded as an open question rather than resolved here.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Neurodevelopmental_Disorder_with_or_without_Anomalies_of_the_Brain,_Eye,_or_Heart.html#pathophysiology-deregulated-developmental-morphogen-signaling","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ANeurodevelopmental_Disorder_with_or_without_Anomalies_of_the_Brain_Eye_or_Heart:pathophysiology:Disrupted%20Ocular%20Morphogenesis%20and%20Retinal%20Cell%20Loss","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Disrupted Ocular Morphogenesis and Retinal Cell Loss","description":"Two separable ocular mechanisms operate. First, a patterning defect: the zebrafish rerea (babyface) mutant recapitulates the optic fissure closure defect seen in humans, arising from expansion of the proximal retinal optic stalk and reduced expression of ventral retinal fate genes; inhibiting shh signaling with HPI-1 rescues the coloboma, establishing deregulated shh as causal in that model. Second, a cell-survival defect: RERE is expressed in a subset of retinal ganglion cells, the lens epithelium, and the ciliary body, and RERE-deficient mice show apoptosis of retinal cells in the ganglion cell layer from E17.5, reduced retinal ganglion cell numbers, and consequent retinal and optic nerve atrophy. Together these account for the coloboma, microphthalmia, and optic nerve findings of NEDBEH.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Neurodevelopmental_Disorder_with_or_without_Anomalies_of_the_Brain,_Eye,_or_Heart.html#pathophysiology-disrupted-ocular-morphogenesis-and-retinal-cell-loss","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ANeurodevelopmental_Disorder_with_or_without_Anomalies_of_the_Brain_Eye_or_Heart:pathophysiology:Impaired%20RERE-Dependent%20Retinoic%20Acid%20Signaling","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired RERE-Dependent Retinoic Acid Signaling","description":"RERE is a positive regulator of retinoic acid (RA) signaling. It forms a complex with NR2F2, p300, and a retinoic acid receptor that is recruited to the retinoic acid response elements of RA target genes such as the Rarb promoter, and knockdown of NR2F2 and/or RERE decreases RA signaling. RERE is also the co-repressor-recruiting subunit of the WHHERE complex (Wdr5, Hdac1, Hdac2, Rere), which together with the RERE-binding histone methyltransferase Ehmt2/G9a becomes enriched at RA target genes upon RA treatment to promote RNA polymerase II recruitment. Loss of this activity blunts the RA-dependent transcriptional programs that pattern the embryo. Because RA acts as a morphogen across hindbrain, eye, heart, otic, and renal development, a single lesion here propagates into anomalies of several organs at once.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Neurodevelopmental_Disorder_with_or_without_Anomalies_of_the_Brain,_Eye,_or_Heart.html#pathophysiology-impaired-rere-dependent-retinoic-acid-signaling","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Neurodevelopmental_Disorder_with_or_without_Anomalies_of_the_Brain_Eye_or_Heart.yaml:ReMut CRISPR/Cas9 RERE frameshift knock-in cell line","source_id":"model:kb/disorders/Neurodevelopmental_Disorder_with_or_without_Anomalies_of_the_Brain_Eye_or_Heart.yaml:ReMut CRISPR/Cas9 RERE frameshift knock-in cell line","target_id":"node:disorder%3ANeurodevelopmental_Disorder_with_or_without_Anomalies_of_the_Brain_Eye_or_Heart:pathophysiology:Deregulated%20Developmental%20Morphogen%20Signaling","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Measures","directed":false,"relationship":"MEASURES","fidelity":"LOW","causal_link_type":null,"causal_link_type_label":null,"description":"The line measures transcriptomic and proteomic consequences of a patient RERE frameshift allele, including the direction of SHH pathway change and perturbation of the WHHERE complex deacetylases.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ANeurodevelopmental_Disorder_with_or_without_Anomalies_of_the_Brain_Eye_or_Heart:2:0","source_id":"node:disorder%3ANeurodevelopmental_Disorder_with_or_without_Anomalies_of_the_Brain_Eye_or_Heart:pathophysiology:Deregulated%20Developmental%20Morphogen%20Signaling","target_id":"node:disorder%3ANeurodevelopmental_Disorder_with_or_without_Anomalies_of_the_Brain_Eye_or_Heart:pathophysiology:Disrupted%20Ocular%20Morphogenesis%20and%20Retinal%20Cell%20Loss","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Deregulated shh/fgf8 signaling expands the optic stalk and prevents the optic fissure margins from apposing.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ANeurodevelopmental_Disorder_with_or_without_Anomalies_of_the_Brain_Eye_or_Heart:1:0","source_id":"node:disorder%3ANeurodevelopmental_Disorder_with_or_without_Anomalies_of_the_Brain_Eye_or_Heart:pathophysiology:Impaired%20RERE-Dependent%20Retinoic%20Acid%20Signaling","target_id":"node:disorder%3ANeurodevelopmental_Disorder_with_or_without_Anomalies_of_the_Brain_Eye_or_Heart:pathophysiology:Deregulated%20Developmental%20Morphogen%20Signaling","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"RA-dependent transcriptional programs constrain SHH and FGF8 signaling during patterning; losing that constraint deregulates them.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0}]}}],"mechanism_names":["Deregulated Developmental Morphogen Signaling"],"relationships":["Measures"],"fidelities":["Low"],"biological_scales":["Cellular"],"system_context_sources":["Linked mechanism biological scale"],"modeled_system_labels":["Cellular"],"biological_process_terms":[{"id":"GO:0007224","label":"smoothened signaling pathway","display_label":"smoothened signaling pathway","url":"http://purl.obolibrary.org/obo/GO_0007224"}],"biological_processes":["smoothened signaling pathway"],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":["HDAC1 and HDAC2 abundance"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:38018232","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38018232","reference_title":"A de novo variant in RERE causes autistic behavior by disrupting related genes and signaling pathway.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"we generated an RERE point mutation cell line (ReMut) using CRISPR/Cas9 Targeted Genome Editing","explanation":"Establishes the existence and construction of the patient-variant-matched cell line."},{"reference":"PMID:38018232","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38018232","reference_title":"A de novo variant in RERE causes autistic behavior by disrupting related genes and signaling pathway.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We identified 3790 differentially expressed genes and 684 differentially expressed proteins.","explanation":"Establishes that the line yields genome-wide molecular readouts. Marked PARTIAL because a differential-expression count supports that the model measures something, not that it faithfully represents the human mechanism — hence the LOW fidelity."},{"reference":"PMID:38018232","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38018232","reference_title":"A de novo variant in RERE causes autistic behavior by disrupting related genes and signaling pathway.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"we noted alterations in HDAC1 and HDAC2, which are members of the WHHERE complex, suggesting their role in the pathogenesis of this patient","explanation":"The measured change in WHHERE complex components grounding this readout."}],"evidence_text":["we generated an RERE point mutation cell line (ReMut) using CRISPR/Cas9 Targeted Genome Editing","We identified 3790 differentially expressed genes and 684 differentially expressed proteins.","we noted alterations in HDAC1 and HDAC2, which are members of the WHHERE complex, suggesting their role in the pathogenesis of this patient","Establishes the existence and construction of the patient-variant-matched cell line.","Establishes that the line yields genome-wide molecular readouts. 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transduction"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:24901367","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/24901367","reference_title":"Defective i6A37 modification of mitochondrial and cytosolic tRNAs results from pathogenic mutations in TRIT1 and its substrate tRNA.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Complete complementation of the i6A37 deficiency of both cytosolic and mitochondrial tRNAs was achieved by transduction of patient fibroblasts with wild-type TRIT1.","explanation":"Shows this system is informative for the modification node."},{"reference":"PMID:24901367","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/24901367","reference_title":"Defective i6A37 modification of mitochondrial and cytosolic tRNAs results from pathogenic mutations in TRIT1 and its substrate 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Cells are generated by ex vivo differentiation rather than surviving in a circulation, so red cell lifespan itself cannot be measured.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[{"id":"CL:0000232","label":"erythrocyte","display_label":"erythrocyte","url":"http://purl.obolibrary.org/obo/CL_0000232"}],"biological_processes":[{"id":"GO:0072488","label":"ammonium transmembrane transport","display_label":"ammonium transmembrane transport by the Rh complex","url":"http://purl.obolibrary.org/obo/GO_0072488"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[],"evidence":[{"reference":"PMID:23417980","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/23417980","reference_title":"In vitro generated Rh(null) red cells recapitulate the in vivo deficiency: a model for rare blood group phenotypes and erythroid membrane disorders.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"we were able to reveal for the first time that RhAG extinction alone is sufficient to explain ICAM-4 and CD47 loss observed on native Rh(null) RBCs","explanation":"The sufficiency claim this model establishes, which is what makes it informative for the complex-assembly node rather than merely consistent with it."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Rh_Deficiency_Syndrome","model_node_id":"model:kb/disorders/Rh_Deficiency_Syndrome.yaml:RhAG-knockdown ex vivo erythroid model","focus_node_id":"node:disorder%3ARh_Deficiency_Syndrome:pathophysiology:Absent%20or%20Severely%20Reduced%20Rh%20Membrane%20Complex","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Rh_Deficiency_Syndrome.html#pathograph","nodes":[{"id":"model:kb/disorders/Rh_Deficiency_Syndrome.yaml:RhAG-knockdown ex vivo erythroid model","kind":"experimental_model","kind_label":"NAM model","label":"RhAG-knockdown ex vivo erythroid model","description":"Lentiviral knockdown of RhAG in cells undergoing ex vivo erythroid differentiation, generating red cells that reproduce the native Rh-null phenotype. 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The magnitude of residual rRNA cleavage tracks skeletal severity across the CHH-AD spectrum, and CHH sits where enough activity is retained to avoid the anauxetic skeleton but not enough to build a normal growth plate.","url":"https://dismech.monarchinitiative.org/pages/disorders/Cartilage-hair_hypoplasia.html#pathophysiology-impaired-pre-rrna-processing-and-ribosome-biogenesis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACartilage-Hair_Hypoplasia:phenotype:Joint%20hypermobility","kind":"phenotype","kind_label":"Phenotype","label":"Joint hypermobility","description":"Generalized ligamentous laxity, present in the large majority of patients and coexisting paradoxically with restricted elbow extension.","url":"https://dismech.monarchinitiative.org/pages/disorders/Cartilage-hair_hypoplasia.html#phenotype-joint-hypermobility","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACartilage-Hair_Hypoplasia:phenotype:Limited%20elbow%20extension","kind":"phenotype","kind_label":"Phenotype","label":"Limited elbow extension","description":"Incomplete extension of the elbows, present in the great majority of patients despite generalized laxity elsewhere.","url":"https://dismech.monarchinitiative.org/pages/disorders/Cartilage-hair_hypoplasia.html#phenotype-limited-elbow-extension","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACartilage-Hair_Hypoplasia:pathophysiology:Loss%20of%20RMRP-Derived%20Small%20RNA%20Gene%20Silencing","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Loss of RMRP-Derived Small RNA Gene Silencing","description":"A fourth arm that is easy to overlook and is the best available explanation for the hair phenotype specifically, which the ribosome arm accounts for poorly. 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Their regulatory targets are enriched for skeletal development, hair development and haematopoietic differentiation programmes, naming PTCH2 and SOX4 among others, so the disease may be as much a disorder of lost small-RNA regulation as of lost cleavage activity.","url":"https://dismech.monarchinitiative.org/pages/disorders/Cartilage-hair_hypoplasia.html#pathophysiology-loss-of-rmrp-derived-small-rna-gene-silencing","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACartilage-Hair_Hypoplasia:phenotype:Lumbar%20hyperlordosis","kind":"phenotype","kind_label":"Phenotype","label":"Lumbar hyperlordosis","description":"Exaggerated lumbar lordosis, part of the characteristic skeletal habitus.","url":"https://dismech.monarchinitiative.org/pages/disorders/Cartilage-hair_hypoplasia.html#phenotype-lumbar-hyperlordosis","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACartilage-Hair_Hypoplasia:phenotype:Metaphyseal%20chondrodysplasia","kind":"phenotype","kind_label":"Phenotype","label":"Metaphyseal chondrodysplasia","description":"Metaphyseal dysplasia with flaring, cupping, widening, cysts, fragmentation and scalloping of the metaphyses, most marked at the knee. 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This is a variant-function assay rather than a disease model: it measures the molecular node, and does not reproduce any neurodevelopmental phenotype.","url":"https://dismech.monarchinitiative.org/pages/disorders/ReNU_Syndrome.html#experimental-model-saturation-genome-editing-of-rnu4-2-in-hap1-cells","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AReNU_Syndrome:pathophysiology:RNU4-2%20Critical-Region%20Variant%20Disrupts%20U4%20snRNA%20%2F%20Spliceosome%20Function","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"RNU4-2 Critical-Region Variant Disrupts U4 snRNA / Spliceosome Function","description":"RNU4-2 encodes the U4 small nuclear RNA, which base-pairs extensively with U6 snRNA within the U4/U6.U5 tri-snRNP of the major spliceosome. 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Note that this is not a loss-of-function mechanism: biallelic variants elsewhere in RNU4-2 reduce transcript levels and cause a separate recessive disorder, which is what distinguishes ReNU syndrome mechanistically from simple haploinsufficiency.","url":"https://dismech.monarchinitiative.org/pages/disorders/ReNU_Syndrome.html#pathophysiology-rnu4-2-critical-region-variant-disrupts-u4-snrna-spliceosome-function","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AReNU_Syndrome:pathophysiology:Systematic%20Disruption%20of%205%27%20Splice-Site%20Usage","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Systematic Disruption of 5' Splice-Site Usage","description":"RNA sequencing of individuals with RNU4-2 variants shows systematically disrupted 5' splice-site usage — notably increased use of unannotated 5' splice sites — consistent with the known role of the affected region during spliceosome activation. This global splicing dysregulation during neurodevelopment is the proposed convergence point linking the RNA-level defect to the neurodevelopmental phenotype, placing ReNU syndrome among the spliceosomopathies. Because the spliceosome is used by essentially every transcript, the downstream consequences are not confined to brain: skeletal and, in at least one report, glomerular involvement are part of the phenotype. Which downstream transcripts actually mediate each organ phenotype is not known, so the edges below are curated as indirect with unknown intermediates.","url":"https://dismech.monarchinitiative.org/pages/disorders/ReNU_Syndrome.html#pathophysiology-systematic-disruption-of-5-splice-site-usage","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/ReNU_Syndrome.yaml:Saturation genome editing of RNU4-2 in HAP1 cells","source_id":"model:kb/disorders/ReNU_Syndrome.yaml:Saturation genome editing of RNU4-2 in HAP1 cells","target_id":"node:disorder%3AReNU_Syndrome:pathophysiology:RNU4-2%20Critical-Region%20Variant%20Disrupts%20U4%20snRNA%20%2F%20Spliceosome%20Function","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Measures","directed":false,"relationship":"MEASURES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"Quantifies the functional consequence of each RNU4-2 variant, resolving the critical region to single-nucleotide resolution and reclassifying variants of uncertain 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fitness)"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:41951737","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41951737","reference_title":"Saturation editing of RNU4-2 reveals distinct dominant and recessive disorders.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Here we performed saturation genome editing (SGE) of RNU4-2 to identify the functional and clinical impact of variants across the entire gene.","explanation":"Establishes the existence and purpose of the model system curated here."},{"reference":"PMID:41951737","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41951737","reference_title":"Saturation editing of RNU4-2 reveals distinct dominant and recessive disorders.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Lacking established models for assaying RNU4-2 variants, we chose to perform SGE in HAP1 cells, a haploid human line in which growth effects have accurately distinguished pathogenic variants across several protein-coding genes","explanation":"States both the rationale for the model and, by naming the absence of established models, why it is informative for this node."},{"reference":"PMID:41951737","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41951737","reference_title":"Saturation editing of RNU4-2 reveals distinct dominant and recessive disorders.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The resulting SGE function scores, derived from variants' effects on cell fitness, discriminate ReNU syndrome variants from those observed in the population and markedly outperform in silico variant effect prediction","explanation":"Defines the readout and establishes that it discriminates pathogenic from population variation better than computational prediction."}],"evidence_text":["Here we performed saturation genome editing (SGE) of RNU4-2 to identify the functional and clinical impact of variants across the entire gene.","Lacking established models for assaying RNU4-2 variants, we chose to perform SGE in HAP1 cells, a haploid human line in which growth effects have accurately distinguished pathogenic variants across several protein-coding genes","The resulting SGE function scores, derived from variants' effects on cell fitness, discriminate ReNU syndrome variants from those observed in the population and markedly outperform in silico variant effect prediction","Establishes the existence and purpose of the model system curated here.","States both the rationale for the model and, by naming the absence of established models, why it is informative for this node.","Defines the readout and establishes that it discriminates pathogenic from population variation better than computational prediction."],"evidence_status":"Evidence recorded","metadata_completeness":80,"metadata_present":["Model category","NAMO 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Examples: HepG2, A549, Caco-2, etc.","namo_docs_url":"https://monarch-initiative.github.io/namo/elements/CellLineModel/","namo_ontology_url":"https://w3id.org/monarch-initiative/namo/CellLineModel","namo_mapping_basis":"Safe mapping from DisMech category","namo_class_in_schema":true,"namo_schema_status":"Defined in NAMO schema used for this build","modality":"Cellular system","organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":null,"source_category":"Immortalized / cell line","culture_system":null,"publication":"PMID:39262789","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39262789","mechanisms":[{"target":"Lathosterol Accumulation","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Lathosterolosis.html#pathophysiology-lathosterol-accumulation","relationship":"RECAPITULATES","relationship_label":"Recapitulates","fidelity":"MODERATE","fidelity_label":"Moderate","description":"Reproduces lathosterol accumulation in a hepatocyte background and shows it produces a distinct transcriptional response from the accumulation of other sterols in the same pathway.","limitations":"A transformed hepatoma line with a complete knockout, so it models neither the hypomorphic alleles patients carry nor the developmental context in which the malformations arise.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[],"biological_processes":[],"pathways":[],"genes":[],"chemicals":[],"readouts":[],"evidence":[{"reference":"PMID:39262789","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39262789","reference_title":"Knockouts of CYP51A1, DHCR24, or SC5D from cholesterol synthesis reveal pathways modulated by sterol intermediates.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Surprisingly, KOs of CYP51, DHCR24, and SC5D shared only 9% of differentially expressed genes.","explanation":"Shows that which sterol accumulates, not merely that cholesterol synthesis is blocked, determines the cellular response - the point the model exists to make."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Lathosterolosis","model_node_id":"model:kb/disorders/Lathosterolosis.yaml:SC5D-knockout HepG2 cell line","focus_node_id":"node:disorder%3ALathosterolosis:pathophysiology:Lathosterol%20Accumulation","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Lathosterolosis.html#pathograph","nodes":[{"id":"model:kb/disorders/Lathosterolosis.yaml:SC5D-knockout HepG2 cell line","kind":"experimental_model","kind_label":"NAM model","label":"SC5D-knockout HepG2 cell line","description":"One of three cholesterol-synthesis enzyme knockouts made in the same hepatocyte background, which allows the consequences of accumulating different sterols to be compared while holding the pathway and cell type constant.","url":"https://dismech.monarchinitiative.org/pages/disorders/Lathosterolosis.html#experimental-model-sc5d-knockout-hepg2-cell-line","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALathosterolosis:pathophysiology:Lathosterol%20Accumulation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Lathosterol Accumulation","description":"Plasma and tissue lathosterol rise, in the reported mild case to more than tenfold above the upper limit of the control range. Accumulation is the diagnostic signature and appears to drive the storage arm of the disease specifically.","url":"https://dismech.monarchinitiative.org/pages/disorders/Lathosterolosis.html#pathophysiology-lathosterol-accumulation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALathosterolosis:pathophysiology:Deficient%20Sterol%20C5-Desaturase%20Activity","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Deficient Sterol C5-Desaturase Activity","description":"The conversion of lathosterol to 7-dehydrocholesterol, the penultimate step of cholesterol synthesis, is blocked.","url":"https://dismech.monarchinitiative.org/pages/disorders/Lathosterolosis.html#pathophysiology-deficient-sterol-c5-desaturase-activity","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALathosterolosis:pathophysiology:Lysosomal%20Lamellar%20Inclusion%20Formation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Lysosomal Lamellar Inclusion Formation","description":"Lamellar inclusions on electron microscopy, with a mucolipidosis-like appearance on light microscopy in the most severely affected. This storage component is what makes lathosterolosis unusual among the cholesterol biosynthesis defects.","url":"https://dismech.monarchinitiative.org/pages/disorders/Lathosterolosis.html#pathophysiology-lysosomal-lamellar-inclusion-formation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALathosterolosis:pathophysiology:Progressive%20Liver%20Disease","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Progressive Liver Disease","description":"Ranges from normal liver function tests through transaminitis to portal fibrosis and cirrhosis. 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alpha-SMA does not separate from unstimulated control until day 8, the caveat recorded in this link's limitations."},{"reference":"PMID:33521022","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33521022","reference_title":"Macromolecular Crowding as a Tool to Screen Anti-fibrotic Drugs: The Scar-in-a-Jar System Revisited.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"a significant increase is seen in mRNA levels of genes encoding COL1A1, COL5A1, and FN1EDA (extracellular matrix proteins), SERPINH1 and PLOD2 (collagen-processing proteins), ACTA2 (a marker for myofibroblasts) and XBP1","explanation":"Reports a significant rise in ACTA2, the myofibroblast marker gene, in primary adult human dermal fibroblasts under TGF-beta 1, which is the direction this readout records."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"module:fibrotic_response","model_node_id":"model:kb/modules/fibrotic_response.yaml:Scar-in-a-Jar macromolecular-crowding fibroblast fibrosis assay","focus_node_id":"node:module%3Afibrotic_response:pathophysiology:Mesenchymal%20Cell%20Activation","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/modules/fibrotic_response.html#pathograph","nodes":[{"id":"model:kb/modules/fibrotic_response.yaml:Scar-in-a-Jar macromolecular-crowding fibroblast fibrosis assay","kind":"experimental_model","kind_label":"NAM model","label":"Scar-in-a-Jar macromolecular-crowding fibroblast fibrosis assay","description":"A macromolecular-crowding culture system in which an inert crowder added to the medium excludes volume and thereby accelerates procollagen processing and extracellular deposition, producing a quantifiable collagen matrix in days rather than weeks. 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The same platform has been run with embryonic and adult lung fibroblasts, embryonic and adult dermal fibroblasts, corneal keratocytes and vocal fold fibroblasts, so the two nodes it is linked to here are exercised without committing to an organ.","url":"https://dismech.monarchinitiative.org/pages/modules/fibrotic_response.html#experimental-models","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:module%3Afibrotic_response:pathophysiology:Mesenchymal%20Cell%20Activation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Mesenchymal Cell Activation","description":"Resident mesenchymal cells (fibroblasts, hepatic stellate cells, pericytes, or mesangial cells depending on organ) are activated by TGF-beta and other pro-fibrotic signals to transdifferentiate into alpha-SMA-positive myofibroblasts. 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This inflammatory phase bridges tissue injury to mesenchymal cell activation and is a key amplification step in the fibrotic cascade.","url":"https://dismech.monarchinitiative.org/pages/modules/fibrotic_response.html#module-pathophysiology-inflammatory-recruitment-and-amplification","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/modules/fibrotic_response.yaml:Scar-in-a-Jar macromolecular-crowding fibroblast fibrosis assay","source_id":"model:kb/modules/fibrotic_response.yaml:Scar-in-a-Jar macromolecular-crowding fibroblast fibrosis assay","target_id":"node:module%3Afibrotic_response:pathophysiology:Mesenchymal%20Cell%20Activation","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"Recombinant TGF-beta 1 drives resident fibroblasts through the defining transition of this node - conversion to an alpha-smooth-muscle-actin positive myofibroblast - and the conversion is measured directly by alpha-SMA staining or ELISA rather than inferred from downstream matrix.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:module%3Afibrotic_response:1:0","source_id":"node:module%3Afibrotic_response:pathophysiology:Inflammatory%20Recruitment%20and%20Amplification","target_id":"node:module%3Afibrotic_response:pathophysiology:Mesenchymal%20Cell%20Activation","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[0]","label":"Causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":null,"causal_link_type_label":null,"description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:module%3Afibrotic_response:2:0","source_id":"node:module%3Afibrotic_response:pathophysiology:Mesenchymal%20Cell%20Activation","target_id":"node:module%3Afibrotic_response:pathophysiology:Excessive%20ECM%20Deposition","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[0]","label":"Causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":null,"causal_link_type_label":null,"description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0}]}},{"target":"Excessive ECM Deposition","target_url":"https://dismech.monarchinitiative.org/pages/modules/fibrotic_response.html#pathophysiology-excessive-ecm-deposition","relationship":"RECAPITULATES","relationship_label":"Recapitulates","fidelity":"MODERATE","fidelity_label":"Moderate","description":"The point of the crowding step is to make deposited matrix the net read-out. 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The degradation arm is only partly covered: collagenolytic enzyme transcripts (MMP1, CTSK) are measured and fall, but TIMP-mediated blockade of matrix turnover is not measured, and no readout captures net matrix turnover directly.","biological_scale":"TISSUE","anatomy":[],"cell_types":[{"id":"CL:0000186","label":"myofibroblast cell","display_label":"Myofibroblast","url":"http://purl.obolibrary.org/obo/CL_0000186"}],"biological_processes":[{"id":"GO:0030198","label":"extracellular matrix organization","display_label":"ECM Organization","url":"http://purl.obolibrary.org/obo/GO_0030198"},{"id":"GO:0032964","label":"collagen biosynthetic process","display_label":"Collagen Biosynthesis","url":"http://purl.obolibrary.org/obo/GO_0032964"},{"id":"GO:0030199","label":"collagen fibril organization","display_label":"Collagen Fibril Organization","url":"http://purl.obolibrary.org/obo/GO_0030199"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Type I and type VI collagen formation (PRO-C1, PRO-C6)","description":null,"target":"Excessive ECM Deposition","direction":"INCREASED","interpretation":"Elevated collagen formation biomarkers are the direct measurement of the excessive matrix production this node names.","biological_processes":[{"id":"GO:0032964","label":"collagen biosynthetic process","display_label":"Collagen Biosynthesis","url":"http://purl.obolibrary.org/obo/GO_0032964"}],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:32381012","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/32381012","reference_title":"Prolonged Scar-in-a-Jar: an in vitro screening tool for anti-fibrotic therapies using biomarkers of extracellular matrix synthesis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Biomarkers of ECM synthesis were evaluated over time in cell supernatants using ELISAs to assess type I, III, IV, V and VI collagen formation (PRO-C1, PRO-C3, PRO-C4, PRO-C5, PRO-C6), fibronectin (FBN-C) deposition and α-smooth muscle actin (α-SMA) expression.","explanation":"Establishes the ELISA modality and the supernatant compartment these markers are measured in, which this readout's interpretation depends on. It does not by itself establish the direction."},{"reference":"PMID:32381012","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/32381012","reference_title":"Prolonged Scar-in-a-Jar: an in vitro screening tool for anti-fibrotic therapies using biomarkers of extracellular matrix synthesis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"TGF-β1 induced synthesis of PRO-C1, PRO-C6 and FBN-C as compared with unstimulated fibroblasts at all timepoints","explanation":"Reports PRO-C1 and PRO-C6 rising against unstimulated fibroblasts at every timepoint measured, which is the direction this readout records."}],"notes":null},{"name":"Fibronectin deposition (FBN-C)","description":null,"target":"Excessive ECM Deposition","direction":"INCREASED","interpretation":"Fibronectin rises alongside collagen under TGF-beta 1, showing the node is exercised beyond a single matrix protein.","biological_processes":[{"id":"GO:0030198","label":"extracellular matrix organization","display_label":"ECM Organization","url":"http://purl.obolibrary.org/obo/GO_0030198"}],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:32381012","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/32381012","reference_title":"Prolonged Scar-in-a-Jar: an in vitro screening tool for anti-fibrotic therapies using biomarkers of extracellular matrix synthesis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"TGF-β1 induced synthesis of PRO-C1, PRO-C6 and FBN-C as compared with unstimulated fibroblasts at all timepoints","explanation":"Reports fibronectin deposition rising under TGF-beta 1 relative to unstimulated fibroblasts at every timepoint measured."}],"notes":null},{"name":"Collagen-degrading enzyme transcripts (MMP1, CTSK)","description":null,"target":"Excessive ECM Deposition","direction":"DECREASED","interpretation":"MMP1 and CTSK fall under TGF-beta 1 while the matrix genes rise, so the system reproduces part of the production-versus-degradation imbalance the node names rather than production alone.","biological_processes":[{"id":"GO:0030198","label":"extracellular matrix organization","display_label":"ECM Organization","url":"http://purl.obolibrary.org/obo/GO_0030198"}],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:33521022","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33521022","reference_title":"Macromolecular Crowding as a Tool to Screen Anti-fibrotic Drugs: The Scar-in-a-Jar System Revisited.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"whereas a significant decrease was seen in mRNA levels of genes encoding for MMP1 and CTSK (enzymes that are able to degrade collagen)","explanation":"Reports the direction of change in two collagen-degrading enzymes in the same dermal fibroblast experiment that shows the matrix genes rise."}],"notes":null}],"evidence":[{"reference":"PMID:34028741","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/34028741","reference_title":"The Scar-in-a-Jar: In Vitro Fibrosis Model for Anti-Fibrotic Drug Testing.","supports":"SUPPORT","evidence_source":"OTHER","snippet":"an in vitro fibrosis model for anti-fibrotic drug testing that benefits from a substantially accelerated extracellular matrix deposition employing macromolecular crowding","explanation":"Establishes that accelerated extracellular matrix deposition is what the assay is built to produce and measure, which is this node."},{"reference":"PMID:32381012","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/32381012","reference_title":"Prolonged Scar-in-a-Jar: an in vitro screening tool for anti-fibrotic therapies using biomarkers of extracellular matrix synthesis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Biomarkers of ECM synthesis were evaluated over time in cell supernatants using ELISAs to assess type I, III, IV, V and VI collagen formation (PRO-C1, PRO-C3, PRO-C4, PRO-C5, PRO-C6), fibronectin (FBN-C) deposition and α-smooth muscle actin (α-SMA) expression.","explanation":"Establishes the ELISA modality and the supernatant compartment these markers are measured in, which this readout's interpretation depends on. It does not by itself establish the direction."},{"reference":"PMID:32381012","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/32381012","reference_title":"Prolonged Scar-in-a-Jar: an in vitro screening tool for anti-fibrotic therapies using biomarkers of extracellular matrix synthesis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"TGF-β1 induced synthesis of PRO-C1, PRO-C6 and FBN-C as compared with unstimulated fibroblasts at all timepoints","explanation":"Reports PRO-C1 and PRO-C6 rising against unstimulated fibroblasts at every timepoint measured, which is the direction this readout records."},{"reference":"PMID:33521022","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33521022","reference_title":"Macromolecular Crowding as a Tool to Screen Anti-fibrotic Drugs: The Scar-in-a-Jar System Revisited.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"whereas a significant decrease was seen in mRNA levels of genes encoding for MMP1 and CTSK (enzymes that are able to degrade collagen)","explanation":"Reports the direction of change in two collagen-degrading enzymes in the same dermal fibroblast experiment that shows the matrix genes rise."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"module:fibrotic_response","model_node_id":"model:kb/modules/fibrotic_response.yaml:Scar-in-a-Jar macromolecular-crowding fibroblast fibrosis assay","focus_node_id":"node:module%3Afibrotic_response:pathophysiology:Excessive%20ECM%20Deposition","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/modules/fibrotic_response.html#pathograph","nodes":[{"id":"model:kb/modules/fibrotic_response.yaml:Scar-in-a-Jar macromolecular-crowding fibroblast fibrosis assay","kind":"experimental_model","kind_label":"NAM model","label":"Scar-in-a-Jar macromolecular-crowding fibroblast fibrosis assay","description":"A macromolecular-crowding culture system in which an inert crowder added to the medium excludes volume and thereby accelerates procollagen processing and extracellular deposition, producing a quantifiable collagen matrix in days rather than weeks. 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alpha-SMA does not separate from unstimulated control until day 8, the caveat recorded in this link's limitations."},{"reference":"PMID:33521022","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33521022","reference_title":"Macromolecular Crowding as a Tool to Screen Anti-fibrotic Drugs: The Scar-in-a-Jar System Revisited.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"a significant increase is seen in mRNA levels of genes encoding COL1A1, COL5A1, and FN1EDA (extracellular matrix proteins), SERPINH1 and PLOD2 (collagen-processing proteins), ACTA2 (a marker for myofibroblasts) and XBP1","explanation":"Reports a significant rise in ACTA2, the myofibroblast marker gene, in primary adult human dermal fibroblasts under TGF-beta 1, which is the direction this readout records."},{"reference":"PMID:34028741","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/34028741","reference_title":"The Scar-in-a-Jar: In Vitro Fibrosis Model for Anti-Fibrotic Drug Testing.","supports":"SUPPORT","evidence_source":"OTHER","snippet":"an in vitro fibrosis model for anti-fibrotic drug testing that benefits from a substantially accelerated extracellular matrix deposition employing macromolecular crowding","explanation":"Establishes that accelerated extracellular matrix deposition is what the assay is built to produce and measure, which is this node."},{"reference":"PMID:32381012","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/32381012","reference_title":"Prolonged Scar-in-a-Jar: an in vitro screening tool for anti-fibrotic therapies using biomarkers of extracellular matrix synthesis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Biomarkers of ECM synthesis were evaluated over time in cell supernatants using ELISAs to assess type I, III, IV, V and VI collagen formation (PRO-C1, PRO-C3, PRO-C4, PRO-C5, PRO-C6), fibronectin (FBN-C) deposition and α-smooth muscle actin (α-SMA) expression.","explanation":"Establishes the ELISA modality and the supernatant compartment these markers are measured in, which this readout's interpretation depends on. It does not by itself establish the direction."},{"reference":"PMID:32381012","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/32381012","reference_title":"Prolonged Scar-in-a-Jar: an in vitro screening tool for anti-fibrotic therapies using biomarkers of extracellular matrix synthesis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"TGF-β1 induced synthesis of PRO-C1, PRO-C6 and FBN-C as compared with unstimulated fibroblasts at all timepoints","explanation":"Reports PRO-C1 and PRO-C6 rising against unstimulated fibroblasts at every timepoint measured, which is the direction this readout records."},{"reference":"PMID:33521022","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33521022","reference_title":"Macromolecular Crowding as a Tool to Screen Anti-fibrotic Drugs: The Scar-in-a-Jar System Revisited.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"whereas a significant decrease was seen in mRNA levels of genes encoding for MMP1 and CTSK (enzymes that are able to degrade collagen)","explanation":"Reports the direction of change in two collagen-degrading enzymes in the same dermal fibroblast experiment that shows the matrix genes rise."},{"reference":"PMID:34028741","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/34028741","reference_title":"The Scar-in-a-Jar: In Vitro Fibrosis Model for Anti-Fibrotic Drug Testing.","supports":"SUPPORT","evidence_source":"OTHER","snippet":"employing macromolecular crowding and a collagen-producing cell type of choice (e.g., lung fibroblasts like WI-38)","explanation":"The protocol states the cell type is chosen per experiment, so the system is not defined by any one organ."},{"reference":"PMID:33521022","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33521022","reference_title":"Macromolecular Crowding as a Tool to Screen Anti-fibrotic Drugs: The Scar-in-a-Jar System Revisited.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Human fibroblasts used are WI-38 cells (embryonic lung fibroblasts) (3, 4, 6, 31, 38), WS-1 cells (embryonic dermal fibroblasts) (38, 39), adult dermal fibroblasts (37, 40), adult corneal fibroblasts (keratocytes) (34–36) and immortalized adult vocal fold fibroblasts (32).","explanation":"Enumerates the fibroblast sources the published literature has run this system with, spanning four different organs. 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Human muscle histochemistry in a different discovery-cohort patient showed some COX-negative fibres, a localized complex IV activity readout rather than evidence that every patient has a generalized mitochondrial myopathy.","url":"https://dismech.monarchinitiative.org/pages/disorders/Spinocerebellar_Ataxia,_Autosomal_Recessive_32.html#pathophysiology-mitochondrial-respiratory-impairment","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ASpinocerebellar_Ataxia_Autosomal_Recessive_32:pathophysiology:Mitochondrial%20Hydrogen%20Peroxide%20Accumulation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Mitochondrial Hydrogen Peroxide Accumulation","description":"PRDX3 loss reduces mitochondrial peroxide buffering. 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In yeast, then, i6A37 loss produces a mitochondria-like phenotype through the cytosol.","notes":null,"context_id":"disorder:Combined_Oxidative_Phosphorylation_Deficiency_35","context_kind":"Disorder","disease_name":"Combined Oxidative Phosphorylation Deficiency 35","disease_synonyms":["COXPD35","combined oxidative phosphorylation deficiency type 35","TRIT1 deficiency","TRIT1-related mitochondrial disorder"],"disease_term":{"id":"MONDO:0054742","label":"combined oxidative phosphorylation deficiency 35","display_label":"combined oxidative phosphorylation deficiency 35","url":"http://purl.obolibrary.org/obo/MONDO_0054742"},"experimental_model_type":"OTHER","experimental_model_type_label":"Other","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":null,"source_category":null,"culture_system":null,"publication":null,"publication_url":null,"mechanisms":[{"target":"Reduced tRNA Isopentenyltransferase Activity","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Oxidative_Phosphorylation_Deficiency_35.html#pathophysiology-reduced-trna-isopentenyltransferase-activity","relationship":"PARTIALLY_RECAPITULATES","relationship_label":"Partially Recapitulates","fidelity":"MODERATE","fidelity_label":"Moderate","description":"Shows that the human enzyme works in a heterologous host and that the patient allele loses activity in vivo.","limitations":"Yeast lacks the ms2i6A37 hypermodification found on mammalian mitochondrial tRNAs. Its i6A37 substrate set differs from the human one. Its respiratory phenotype arises through cytosolic tRNA-Tyr rather than through mitochondrial translation, the opposite of what the human patient cells suggest.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[],"biological_processes":[],"pathways":[],"genes":[{"id":"hgnc:20286","label":"TRIT1","display_label":"TRIT1","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/20286"}],"chemicals":[],"readouts":[],"evidence":[{"reference":"PMID:24901367","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/24901367","reference_title":"Defective i6A37 modification of mitochondrial and cytosolic tRNAs results from pathogenic mutations in TRIT1 and its substrate tRNA.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"tit1-deleted yeast carrying the empty vector or mutant TRIT1 showed no recovery of tRNASer(UCA) function (red colonies), but knock-down yeast carrying wild-type TRIT1 or tit1+ showed recovery of tRNASer(UCA) activity (white colonies) similar to wild-type yeast.","explanation":"The p.Arg323Gln enzyme fails to complement the i6A37-dependent tRNA assay that wild-type TRIT1 rescues."},{"reference":"PMID:26857223","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/26857223","reference_title":"Lack of tRNA-i6A modification causes mitochondrial-like metabolic deficiency in S. pombe by limiting activity of cytosolic tRNATyr, not mito-tRNA.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"Thus, S. pombe i6A37 hypomodification-associated metabolic deficiency results from hypoactivity of cy-tRNA, mostly tRNA(Tyr), and unlike human TRIT1-deficiency does not impair mitochondrial translation due to mt-tRNA hypomodification.","explanation":"The species divergence that limits this model."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Combined_Oxidative_Phosphorylation_Deficiency_35","model_node_id":"model:kb/disorders/Combined_Oxidative_Phosphorylation_Deficiency_35.yaml:Schizosaccharomyces pombe tit1-deletion strain complemented with human TRIT1","focus_node_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_35:pathophysiology:Reduced%20tRNA%20Isopentenyltransferase%20Activity","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Oxidative_Phosphorylation_Deficiency_35.html#pathograph","nodes":[{"id":"model:kb/disorders/Combined_Oxidative_Phosphorylation_Deficiency_35.yaml:Schizosaccharomyces pombe tit1-deletion strain complemented with human TRIT1","kind":"experimental_model","kind_label":"NAM model","label":"Schizosaccharomyces pombe tit1-deletion strain complemented with human TRIT1","description":"Fission yeast lacking the TRIT1 homologue grow slowly on glycerol, a respiratory defect. Human wild-type TRIT1 complemented an i6A37-dependent tRNA suppression assay in this strain, and the p.Arg323Gln mutant did not. Later work in the same strain traced the respiratory growth defect to cytosolic tRNA-Tyr, not mitochondrial tRNA. In yeast, then, i6A37 loss produces a mitochondria-like phenotype through the cytosol.","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Oxidative_Phosphorylation_Deficiency_35.html#experimental-model-schizosaccharomyces-pombe-tit1-deletion-strain-complemented-with-human-trit1","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_35:pathophysiology:Reduced%20tRNA%20Isopentenyltransferase%20Activity","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced tRNA Isopentenyltransferase Activity","description":"TRIT1 transfers the dimethylallyl group of dimethylallyl pyrophosphate to N6 of A37. In the founding family the patient protein was present but the cells were severely deficient in the product. Recombinant p.Arg323Gln TRIT1 had lower activity towards several tRNA substrates in vitro. The reduction is substrate-dependent rather than a loss of catalysis. Heavy overexpression of the mutant enzyme restored modification of the cytosolic substrate tested almost fully, but restored the mitochondrial substrate poorly.","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Oxidative_Phosphorylation_Deficiency_35.html#pathophysiology-reduced-trna-isopentenyltransferase-activity","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_35:pathophysiology:Biallelic%20TRIT1%20Variants","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Biallelic TRIT1 Variants","description":"Two damaged copies of TRIT1. The alleles are mostly private. They include homozygous missense variants (p.Arg323Gln in the founding family, p.Met82Ile), compound heterozygous missense, splice and nonsense combinations (p.Glu327Lys with c.682+2T>C; p.Ile109Thr with p.Arg327*; p.Arg323Trp with p.Glu295Glyfs*8), and a homozygous splice-acceptor variant (c.1235-3C>G). p.Arg323Gln does not lower TRIT1 protein levels. It replaces one of a row of basic residues that contact the anticodon stem of the substrate tRNA. Structural modelling put it at substrate binding rather than catalysis. The missense alleles are therefore hypomorphic rather than null.","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Oxidative_Phosphorylation_Deficiency_35.html#pathophysiology-biallelic-trit1-variants","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_35:pathophysiology:i6A37%20Hypomodification%20of%20Cytosolic%20tRNAs","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"i6A37 Hypomodification of Cytosolic tRNAs","description":"The same patient cells lack i6A37 on cytosolic tRNAs, shown for cytosolic tRNA-Ser(UGA). Here, unlike the mitochondrial case, steady-state tRNA levels were not reduced. Whether this half of the lesion contributes to disease is unknown. In fission yeast, loss of the homologous enzyme causes a mitochondria-like respiratory growth defect that is due to cytosolic tRNA-Tyr, not to mitochondrial tRNA. TRIT1 also isopentenylates the selenocysteine tRNA. Patient fibroblasts did not show a general fall in selenoproteins, but neuron-specific Trit1 knockout mice showed a reduction in one brain selenoprotein. No causal edge is drawn from this node. The knowledge-gap discussion records why.","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Oxidative_Phosphorylation_Deficiency_35.html#pathophysiology-i6a37-hypomodification-of-cytosolic-trnas","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_35:pathophysiology:i6A37%20Hypomodification%20of%20Mitochondrial%20tRNAs","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"i6A37 Hypomodification of Mitochondrial tRNAs","description":"Patient fibroblasts were severely deficient in i6A37 on mitochondrial tRNAs, measured on mt-tRNA-Ser(UCN). Wild-type TRIT1 corrected this. The unmodified mt-tRNA-Ser(UCN) was also less stable, with steady-state levels about 40 percent lower. The defect is therefore both less active tRNA and less tRNA. In mammalian mitochondria the i6A37 product is further methylthiolated to ms2i6A37, and both were sharply reduced in blood and urine RNA of a later patient. This gives a non-invasive readout of the same lesion.","url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Oxidative_Phosphorylation_Deficiency_35.html#pathophysiology-i6a37-hypomodification-of-mitochondrial-trnas","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Combined_Oxidative_Phosphorylation_Deficiency_35.yaml:Schizosaccharomyces pombe tit1-deletion strain complemented with human TRIT1","source_id":"model:kb/disorders/Combined_Oxidative_Phosphorylation_Deficiency_35.yaml:Schizosaccharomyces pombe tit1-deletion strain complemented with human TRIT1","target_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_35:pathophysiology:Reduced%20tRNA%20Isopentenyltransferase%20Activity","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Partially Recapitulates","directed":false,"relationship":"PARTIALLY_RECAPITULATES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"Shows that the human enzyme works in a heterologous host and that the patient allele loses activity in vivo.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":2},{"id":"causal:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_35:0:0","source_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_35:pathophysiology:Biallelic%20TRIT1%20Variants","target_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_35:pathophysiology:Reduced%20tRNA%20Isopentenyltransferase%20Activity","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_35:1:1","source_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_35:pathophysiology:Reduced%20tRNA%20Isopentenyltransferase%20Activity","target_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_35:pathophysiology:i6A37%20Hypomodification%20of%20Cytosolic%20tRNAs","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[1]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_35:1:0","source_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_35:pathophysiology:Reduced%20tRNA%20Isopentenyltransferase%20Activity","target_id":"node:disorder%3ACombined_Oxidative_Phosphorylation_Deficiency_35:pathophysiology:i6A37%20Hypomodification%20of%20Mitochondrial%20tRNAs","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0}]}}],"mechanism_names":["Reduced tRNA Isopentenyltransferase Activity"],"relationships":["Partially Recapitulates"],"fidelities":["Moderate"],"biological_scales":["Molecular"],"system_context_sources":["Linked mechanism biological scale"],"modeled_system_labels":["Molecular"],"biological_process_terms":[],"biological_processes":[],"pathway_terms":[],"pathways":[],"gene_terms":[{"id":"hgnc:20286","label":"TRIT1","display_label":"TRIT1","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/20286"}],"genes":["TRIT1"],"chemical_terms":[],"chemicals":[],"readout_names":[],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:24901367","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/24901367","reference_title":"Defective i6A37 modification of mitochondrial and cytosolic tRNAs results from pathogenic mutations in TRIT1 and its substrate tRNA.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"tit1-deleted yeast carrying the empty vector or mutant TRIT1 showed no recovery of tRNASer(UCA) function (red colonies), but knock-down yeast carrying wild-type TRIT1 or tit1+ showed recovery of tRNASer(UCA) activity (white colonies) similar to wild-type yeast.","explanation":"The p.Arg323Gln enzyme fails to complement the i6A37-dependent tRNA assay that wild-type TRIT1 rescues."},{"reference":"PMID:26857223","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/26857223","reference_title":"Lack of tRNA-i6A modification causes mitochondrial-like metabolic deficiency in S. pombe by limiting activity of cytosolic tRNATyr, not mito-tRNA.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"Thus, S. pombe i6A37 hypomodification-associated metabolic deficiency results from hypoactivity of cy-tRNA, mostly tRNA(Tyr), and unlike human TRIT1-deficiency does not impair mitochondrial translation due to mt-tRNA hypomodification.","explanation":"The species divergence that limits this model."}],"evidence_text":["tit1-deleted yeast carrying the empty vector or mutant TRIT1 showed no recovery of tRNASer(UCA) function (red colonies), but knock-down yeast carrying wild-type TRIT1 or tit1+ showed recovery of tRNASer(UCA) activity (white colonies) similar to wild-type yeast.","Thus, S. pombe i6A37 hypomodification-associated metabolic deficiency results from hypoactivity of cy-tRNA, mostly tRNA(Tyr), and unlike human TRIT1-deficiency does not impair mitochondrial translation due to mt-tRNA hypomodification.","The p.Arg323Gln enzyme fails to complement the i6A37-dependent tRNA assay that wild-type TRIT1 rescues.","The species divergence that limits this model."],"evidence_status":"Evidence recorded","metadata_completeness":30,"metadata_present":["Model category","Modeled mechanism","Evidence"],"metadata_missing":["NAMO class","Organism","Anatomy","Cell type","Cell source","Culture system","Publication"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Combined_Oxidative_Phosphorylation_Deficiency_35.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Combined_Oxidative_Phosphorylation_Deficiency_35.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Combined_Oxidative_Phosphorylation_Deficiency_35.html#experimental-model-schizosaccharomyces-pombe-tit1-deletion-strain-complemented-with-human-trit1","source_anchor":"experimental-model-schizosaccharomyces-pombe-tit1-deletion-strain-complemented-with-human-trit1"},{"id":"model:kb/disorders/SCO2-Related_Fatal_Infantile_Cardioencephalomyopathy.yaml:SCO2-mutant patient iPSC-derived cardiomyocytes","name":"SCO2-mutant patient iPSC-derived cardiomyocytes","description":"Cardiomyocytes differentiated via embryoid bodies from induced pluripotent stem cells reprogrammed from skin fibroblasts of two SCO2 patients (one compound heterozygous for p.E140K, one homozygous for p.G193S) and healthy controls. The model captures the human cardiac arm of the disease that viable Sco2 mouse models do not reproduce.\n","notes":null,"context_id":"disorder:SCO2-Related_Fatal_Infantile_Cardioencephalomyopathy","context_kind":"Disorder","disease_name":"SCO2-Related Fatal Infantile Cardioencephalomyopathy","disease_synonyms":["SCO2 deficiency","Fatal infantile cardioencephalomyopathy due to cytochrome c oxidase deficiency 1","Cardioencephalomyopathy, fatal infantile, due to COX deficiency, SCO2-related"],"disease_term":{"id":"MONDO:0011451","label":"cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1","display_label":"SCO2-related fatal infantile cardioencephalomyopathy","url":"http://purl.obolibrary.org/obo/MONDO_0011451"},"experimental_model_type":"IPSC_DERIVED_MODEL","experimental_model_type_label":"iPSC-derived model","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},"organism_label":"Homo sapiens","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[{"id":"CL:0000746","label":"cardiac muscle cell","display_label":"cardiac muscle cell","url":"http://purl.obolibrary.org/obo/CL_0000746"}],"model_cell_type_labels":["cardiac muscle cell"],"linked_cell_types":[{"id":"CL:0000746","label":"cardiac muscle cell","display_label":"cardiac muscle cell","url":"http://purl.obolibrary.org/obo/CL_0000746"}],"linked_cell_type_labels":["cardiac muscle cell"],"cell_types":[{"id":"CL:0000746","label":"cardiac muscle cell","display_label":"cardiac muscle cell","url":"http://purl.obolibrary.org/obo/CL_0000746"}],"cell_type_labels":["cardiac muscle cell"],"conditions":[],"cell_source":null,"source_category":"iPSC-derived","culture_system":null,"publication":"PMID:29193756","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/29193756","mechanisms":[{"target":"Impaired Terminal Electron Transfer and ATP Synthesis","target_url":"https://dismech.monarchinitiative.org/pages/disorders/SCO2-Related_Fatal_Infantile_Cardioencephalomyopathy.html#pathophysiology-impaired-terminal-electron-transfer-and-atp-synthesis","relationship":"RECAPITULATES","relationship_label":"Recapitulates","fidelity":"MODERATE","fidelity_label":"Moderate","description":"SCO2-mutant iPSC-derived cardiomyocytes show ultrastructural mitochondrial abnormalities and blunted inotropic responsiveness, with delayed afterdepolarizations and increased beat-rate variability attributed to impaired sarcoplasmic-reticulum calcium handling secondary to ATP shortage.\n","limitations":"iPSC-derived cardiomyocytes are immature relative to adult myocardium and are studied in isolation from the hemodynamic load and neurohormonal context that shape hypertrophic remodeling in vivo; only two patient genotypes were assayed.\n","biological_scale":"CELLULAR","anatomy":[],"cell_types":[{"id":"CL:0000746","label":"cardiac muscle cell","display_label":"cardiac muscle cell","url":"http://purl.obolibrary.org/obo/CL_0000746"}],"biological_processes":[{"id":"GO:0006123","label":"mitochondrial electron transport, cytochrome c to oxygen","display_label":"mitochondrial electron transport, cytochrome c to oxygen","url":"http://purl.obolibrary.org/obo/GO_0006123"},{"id":"GO:0042775","label":"mitochondrial ATP synthesis coupled electron transport","display_label":"ATP synthesis coupled electron transport","url":"http://purl.obolibrary.org/obo/GO_0042775"},{"id":"GO:0009060","label":"aerobic respiration","display_label":"aerobic respiration","url":"http://purl.obolibrary.org/obo/GO_0009060"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[],"evidence":[{"reference":"PMID:29193756","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/29193756","reference_title":"Investigating the cardiac pathology of SCO2-mediated hypertrophic cardiomyopathy using patients induced pluripotent stem cell-derived cardiomyocytes.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"we found in the mutated iPSC-CMs major ultrastructural abnormalities and markedly attenuated response to the inotropic interventions and caffeine, as well as delayed afterdepolarizations (DADs) and increased BRV, suggesting impaired SR Ca2+ handling due to attenuated SERCA activity caused by ATP shortage.","explanation":"Establishes that the patient-derived cardiomyocyte model reproduces the bioenergetic-failure node with a measurable cardiac functional readout."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:SCO2-Related_Fatal_Infantile_Cardioencephalomyopathy","model_node_id":"model:kb/disorders/SCO2-Related_Fatal_Infantile_Cardioencephalomyopathy.yaml:SCO2-mutant patient iPSC-derived cardiomyocytes","focus_node_id":"node:disorder%3ASCO2-Related_Fatal_Infantile_Cardioencephalomyopathy:pathophysiology:Impaired%20Terminal%20Electron%20Transfer%20and%20ATP%20Synthesis","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/SCO2-Related_Fatal_Infantile_Cardioencephalomyopathy.html#pathograph","nodes":[{"id":"model:kb/disorders/SCO2-Related_Fatal_Infantile_Cardioencephalomyopathy.yaml:SCO2-mutant patient iPSC-derived cardiomyocytes","kind":"experimental_model","kind_label":"NAM model","label":"SCO2-mutant patient iPSC-derived cardiomyocytes","description":"Cardiomyocytes differentiated via embryoid bodies from induced pluripotent stem cells reprogrammed from skin fibroblasts of two SCO2 patients (one compound heterozygous for p.E140K, one homozygous for p.G193S) and healthy controls. 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The endplate is a growth-plate equivalent for the vertebral body, so an irregular endplate is the radiological signature of the same chondro-osseous defect that produces the long-bone findings, rather than a separate lesion.","url":"https://dismech.monarchinitiative.org/pages/disorders/SCUBE3-Related_Short_Stature_Syndrome.html#phenotype-irregular-vertebral-endplates","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ASCUBE3-Related_Short_Stature_Syndrome:pathophysiology:Loss%20of%20SCUBE3%20BMP%20Co-Receptor%20Function","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Loss of SCUBE3 BMP Co-Receptor Function","description":"Biallelic inactivating SCUBE3 variants remove a membrane-associated BMP2/4 co-receptor. Wild-type SCUBE3 attracts BMP receptor complexes to lipid-raft microdomains and enhances BMP signalling, apparently by facilitating the interaction of BMP ligands with BMP type I receptors. The best-characterized illustration of what that loss costs at the protein level is the N294K substitution, which reaches the cell surface normally but fails to complex with BMP type IA receptor - so the defect is in receptor engagement, not in protein trafficking. Read that as mechanism rather than as a patient variant: N294K is a mouse ENU-induced allele and is not among the human variants this entry curates. It is informative here because it sits in the cbEGF7 calcium-binding repeat, the same module the human missense alleles disrupt.","url":"https://dismech.monarchinitiative.org/pages/disorders/SCUBE3-Related_Short_Stature_Syndrome.html#pathophysiology-loss-of-scube3-bmp-co-receptor-function","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ASCUBE3-Related_Short_Stature_Syndrome:phenotype:Microcephaly","kind":"phenotype","kind_label":"Phenotype","label":"Microcephaly","description":null,"url":"https://dismech.monarchinitiative.org/pages/disorders/SCUBE3-Related_Short_Stature_Syndrome.html#phenotype-microcephaly","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ASCUBE3-Related_Short_Stature_Syndrome:phenotype:Narrow%20iliac%20wing","kind":"phenotype","kind_label":"Phenotype","label":"Narrow iliac wing","description":null,"url":"https://dismech.monarchinitiative.org/pages/disorders/SCUBE3-Related_Short_Stature_Syndrome.html#phenotype-narrow-iliac-wing","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ASCUBE3-Related_Short_Stature_Syndrome:phenotype:Radial%20bowing","kind":"phenotype","kind_label":"Phenotype","label":"Radial bowing","description":"Described as mild in the reported case.","url":"https://dismech.monarchinitiative.org/pages/disorders/SCUBE3-Related_Short_Stature_Syndrome.html#phenotype-radial-bowing","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ASCUBE3-Related_Short_Stature_Syndrome:pathophysiology:Reduced%20Growth%20with%20Craniofacial%2C%20Dental%20and%20Skeletal%20Anomalies","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced Growth with Craniofacial, Dental and Skeletal Anomalies","description":"The clinical endpoint: reduced growth with a distinctive craniofacial appearance, dental anomalies and skeletal features.","url":"https://dismech.monarchinitiative.org/pages/disorders/SCUBE3-Related_Short_Stature_Syndrome.html#pathophysiology-reduced-growth-with-craniofacial-dental-and-skeletal-anomalies","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/SCUBE3-Related_Short_Stature_Syndrome.yaml:SCUBE3 loss- and gain-of-function in human bone marrow mesenchymal stem cells","source_id":"model:kb/disorders/SCUBE3-Related_Short_Stature_Syndrome.yaml:SCUBE3 loss- and gain-of-function in human bone marrow mesenchymal stem cells","target_id":"node:disorder%3ASCUBE3-Related_Short_Stature_Syndrome:pathophysiology:Impaired%20BMP-Mediated%20Chondrogenesis%20and%20Osteogenesis","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Perturbs","directed":false,"relationship":"PERTURBS","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"Knockdown impairs osteogenic differentiation; adding back recombinant SCUBE3 raises BMP2 and TGF-beta and restores osteogenic function through SMAD phosphorylation, which is the pathway the disease loses.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ASCUBE3-Related_Short_Stature_Syndrome:1:3","source_id":"node:disorder%3ASCUBE3-Related_Short_Stature_Syndrome:pathophysiology:Impaired%20BMP-Mediated%20Chondrogenesis%20and%20Osteogenesis","target_id":"node:disorder%3ASCUBE3-Related_Short_Stature_Syndrome:phenotype:Irregular%20vertebral%20endplates","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[3]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"The vertebral endplate is a growth-plate equivalent, so its irregularity is read as the vertebral expression of the same chondro-osseous defect. 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Grouped here because cranial bone growth shares the osteogenic defect, but a neural growth mechanism has not been shown.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ASCUBE3-Related_Short_Stature_Syndrome:1:4","source_id":"node:disorder%3ASCUBE3-Related_Short_Stature_Syndrome:pathophysiology:Impaired%20BMP-Mediated%20Chondrogenesis%20and%20Osteogenesis","target_id":"node:disorder%3ASCUBE3-Related_Short_Stature_Syndrome:phenotype:Narrow%20iliac%20wing","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[4]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"The ilium forms by endochondral ossification, so its narrowing is attributed to the same defect. 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pathway.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"SCUBE3 levels increase significantly during early osteogenic differentiation of hBMSCs, and that reducing SCUBE3 levels can hinder this differentiation","explanation":"The measured effect of lowering SCUBE3 on osteogenic differentiation."},{"reference":"PMID:39250278","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39250278","reference_title":"SCUBE3 promotes osteogenic differentiation and mitophagy in human bone marrow mesenchymal stem cells through the BMP2/TGF-beta signaling pathway.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"treatment with recombinant human SCUBE3 (rhSCUBE3) protein boosted BMP2 and TGF-β expression, activated mitophagy in hBMSCs, ameliorated oxidative stress, and restored osteogenic function through SMAD phosphorylation","explanation":"Adding the protein back restores the osteogenic output through SMAD, which is what makes this a pathway claim rather than an 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Co-occurrence does not prove an obligatory retention→ER stress→apoptosis chain.","context_id":"disorder:Autosomal_Dominant_Cutis_Laxa_1","context_kind":"Disorder","disease_name":"Autosomal Dominant Cutis Laxa 1","disease_synonyms":["ADCL1","ELN-related cutis laxa","ELN autosomal dominant cutis laxa","Cutis laxa, autosomal dominant type 1","Autosomal dominant cutis laxa caused by mutation in ELN","Cutis laxa, autosomal dominant"],"disease_term":{"id":"MONDO:0007411","label":"cutis laxa, autosomal dominant 1","display_label":"Autosomal Dominant Cutis Laxa 1","url":"http://purl.obolibrary.org/obo/MONDO_0007411"},"experimental_model_type":"PRIMARY_CELL_CULTURE","experimental_model_type_label":"Primary-cell culture","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[{"id":"CL:0002620","label":"skin fibroblast","display_label":"skin fibroblast","url":"http://purl.obolibrary.org/obo/CL_0002620"}],"model_cell_type_labels":["skin fibroblast"],"linked_cell_types":[{"id":"CL:0002620","label":"skin fibroblast","display_label":"skin fibroblast","url":"http://purl.obolibrary.org/obo/CL_0002620"}],"linked_cell_type_labels":["skin fibroblast"],"cell_types":[{"id":"CL:0002620","label":"skin fibroblast","display_label":"skin fibroblast","url":"http://purl.obolibrary.org/obo/CL_0002620"}],"cell_type_labels":["skin fibroblast"],"conditions":[],"cell_source":"Cultures from CL 1, CL 3 and CL 4 among six individuals/five probands in the 2011 series","source_category":"Primary / biopsy-derived","culture_system":null,"publication":"PMID:21309044","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/21309044","mechanisms":[{"target":"Impaired Elastic Fiber Assembly","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Dominant_Cutis_Laxa_1.html#pathophysiology-impaired-elastic-fiber-assembly","relationship":"PARTIALLY_RECAPITULATES","relationship_label":"Partially Recapitulates","fidelity":"MODERATE","fidelity_label":"Moderate","description":"The patient-culture readout supports this component, with allele-specific differences.","limitations":"Nonisogenic comparisons and no pathway-specific rescue limit causal attribution.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[{"id":"CL:0002620","label":"skin fibroblast","display_label":"skin fibroblast","url":"http://purl.obolibrary.org/obo/CL_0002620"}],"biological_processes":[{"id":"GO:0048251","label":"elastic fiber assembly","display_label":"elastic fiber assembly","url":"http://purl.obolibrary.org/obo/GO_0048251"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[],"evidence":[{"reference":"PMID:21309044","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/21309044","reference_title":"New insights into the pathogenesis of autosomal-dominant cutis laxa with report of five ELN mutations.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We found significantly lower amounts of insoluble elastin in ADCL cells compared to controls on day 4 and 8","explanation":"Cultured patient fibroblasts have reduced mature insoluble elastin deposition relative to the normalization used in the study."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Autosomal_Dominant_Cutis_Laxa_1","model_node_id":"model:kb/disorders/Autosomal_Dominant_Cutis_Laxa_1.yaml:Selected ADCL1 patient dermal fibroblast cultures","focus_node_id":"node:disorder%3AAutosomal_Dominant_Cutis_Laxa_1:pathophysiology:Impaired%20Elastic%20Fiber%20Assembly","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Dominant_Cutis_Laxa_1.html#pathograph","nodes":[{"id":"model:kb/disorders/Autosomal_Dominant_Cutis_Laxa_1.yaml:Selected ADCL1 patient dermal fibroblast cultures","kind":"experimental_model","kind_label":"NAM model","label":"Selected ADCL1 patient dermal fibroblast cultures","description":"Nonisogenic patient fibroblasts and age/sex/passage-matched controls were compared for elastin deposition, splicing and signaling. 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Increased pSMAD2 was observed across all three tested patient cultures.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Dominant_Cutis_Laxa_1.html#experimental-model-selected-adcl1-patient-dermal-fibroblast-cultures","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAutosomal_Dominant_Cutis_Laxa_1:pathophysiology:Impaired%20Elastic%20Fiber%20Assembly","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Elastic Fiber Assembly","description":"Selected patient fibroblasts deposit less insoluble elastin and show abnormal extracellular globules and fibrillar deposition. Recombinant mutant protein also yields less matrix-associated elastin in ARPE-19 culture. Total desmosine per culture protein is lower in that assay, but this does not establish a universal reduction in crosslinks per elastin molecule: crosslinked elastin is increased in some transgenic tissues.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Dominant_Cutis_Laxa_1.html#pathophysiology-impaired-elastic-fiber-assembly","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAutosomal_Dominant_Cutis_Laxa_1:pathophysiology:Abnormal%20Elastic%20Fiber%20Architecture","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Abnormal Elastic Fiber Architecture","description":"Human dermal biopsies show reduced and disorganized elastin deposition, fragmentation and poor association with microfibrils. 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individuals.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[{"id":"CL:0002620","label":"skin fibroblast","display_label":"Dermal fibroblast","url":"http://purl.obolibrary.org/obo/CL_0002620"},{"id":"CL:1000217","label":"growth plate cartilage chondrocyte","display_label":"Growth plate chondrocyte","url":"http://purl.obolibrary.org/obo/CL_1000217"}],"biological_processes":[{"id":"GO:0015012","label":"heparan sulfate proteoglycan biosynthetic process","display_label":"heparan sulfate proteoglycan biosynthetic process","url":"http://purl.obolibrary.org/obo/GO_0015012"},{"id":"GO:0006487","label":"protein N-linked glycosylation","display_label":"protein N-linked glycosylation","url":"http://purl.obolibrary.org/obo/GO_0006487"},{"id":"GO:0006491","label":"N-glycan processing","display_label":"N-Glycan Processing","url":"http://purl.obolibrary.org/obo/GO_0006491"},{"id":"GO:0006493","label":"protein O-linked glycosylation","display_label":"protein O-linked 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This is the organ-agnostic substitution this entry makes against the CDG module's Golgi trigger: the module's generic disruption of Golgi glycosylation machinery is here caused by a luminal ionic lesion rather than by loss of a glycosyltransferase or of a tethering complex.","url":"https://dismech.monarchinitiative.org/pages/disorders/Short_Stature,_Amelogenesis_Imperfecta,_and_Skeletal_Dysplasia_with_Scoliosis.html#pathophysiology-golgi-glycosylation-and-glycosaminoglycan-biosynthesis-defect","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AShort_Stature_Amelogenesis_Imperfecta_And_Skeletal_Dysplasia_With_Scoliosis:pathophysiology:Abnormal%20Glycoprotein%20Glycan%20Profile","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Abnormal Glycoprotein Glycan Profile","description":"The Golgi lesion is readable on circulating glycoproteins. 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The module's expected edge onward to multisystem glycoprotein dysfunction is carried below, but only at the level of the disease as a whole: no study has yet linked a specific hypoglycosylated client protein to a specific SSASKS phenotype, so that edge is graded PARTIAL rather than asserted.","url":"https://dismech.monarchinitiative.org/pages/disorders/Short_Stature,_Amelogenesis_Imperfecta,_and_Skeletal_Dysplasia_with_Scoliosis.html#pathophysiology-abnormal-glycoprotein-glycan-profile","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AShort_Stature_Amelogenesis_Imperfecta_And_Skeletal_Dysplasia_With_Scoliosis:pathophysiology:Cartilage%20and%20Ligament%20Proteoglycan%20Deficiency%20with%20Joint%20Instability","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Cartilage and Ligament Proteoglycan Deficiency with Joint Instability","description":"SSASKS sits nosologically among the dysplasias with multiple joint dislocations, most of which are proteoglycan-biosynthesis disorders, and the reduced heparan sulfate content of cartilage supplies the shared mechanism: proteoglycan-dependent cartilage and periarticular structures are undersupplied, and large joints dislocate. The radiographic signature — advanced carpal ossification with a monkey wrench or Swedish key appearance of the proximal femora — is shared with Desbuquois dysplasia, whose genes CANT1 and XYLT1 also act on the proteoglycan pathway.","url":"https://dismech.monarchinitiative.org/pages/disorders/Short_Stature,_Amelogenesis_Imperfecta,_and_Skeletal_Dysplasia_with_Scoliosis.html#pathophysiology-cartilage-and-ligament-proteoglycan-deficiency-with-joint-instability","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AShort_Stature_Amelogenesis_Imperfecta_And_Skeletal_Dysplasia_With_Scoliosis:pathophysiology:Defective%20Post-Golgi%20Glycoprotein%20Delivery%20to%20the%20Extracellular%20Matrix","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Defective Post-Golgi Glycoprotein Delivery to the Extracellular Matrix","description":"Beyond the composition of the glycans themselves, SLC10A7-deficient fibroblasts fail to move glycoproteins out of the secretory pathway: glycoproteins are mislocalized intracellularly and post-Golgi transport to the cell membrane is defective. 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Because Golgi glycosyltransferase activity and Golgi organization are calcium-dependent, this node is the rate-limiting step linking an orphan transporter to a glycosylation disease.","url":"https://dismech.monarchinitiative.org/pages/disorders/Short_Stature,_Amelogenesis_Imperfecta,_and_Skeletal_Dysplasia_with_Scoliosis.html#pathophysiology-secretory-pathway-calcium-dyshomeostasis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:1:model:kb/disorders/Short_Stature_Amelogenesis_Imperfecta_And_Skeletal_Dysplasia_With_Scoliosis.yaml:SLC10A7-CDG patient dermal fibroblasts","source_id":"model:kb/disorders/Short_Stature_Amelogenesis_Imperfecta_And_Skeletal_Dysplasia_With_Scoliosis.yaml:SLC10A7-CDG patient dermal fibroblasts","target_id":"node:disorder%3AShort_Stature_Amelogenesis_Imperfecta_And_Skeletal_Dysplasia_With_Scoliosis:pathophysiology:Golgi%20Glycosylation%20and%20Glycosaminoglycan%20Biosynthesis%20Defect","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[1]","label":"Measures","directed":false,"relationship":"MEASURES","fidelity":"HIGH","causal_link_type":null,"causal_link_type_label":null,"description":"The heparan sulfate proportion of total glycosaminoglycan is reduced about two-fold, with total glycosaminoglycan preserved.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AShort_Stature_Amelogenesis_Imperfecta_And_Skeletal_Dysplasia_With_Scoliosis:2:0","source_id":"node:disorder%3AShort_Stature_Amelogenesis_Imperfecta_And_Skeletal_Dysplasia_With_Scoliosis:pathophysiology:Golgi%20Glycosylation%20and%20Glycosaminoglycan%20Biosynthesis%20Defect","target_id":"node:disorder%3AShort_Stature_Amelogenesis_Imperfecta_And_Skeletal_Dysplasia_With_Scoliosis:pathophysiology:Abnormal%20Glycoprotein%20Glycan%20Profile","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Defective Golgi processing is detectable on circulating glycoproteins.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AShort_Stature_Amelogenesis_Imperfecta_And_Skeletal_Dysplasia_With_Scoliosis:2:1","source_id":"node:disorder%3AShort_Stature_Amelogenesis_Imperfecta_And_Skeletal_Dysplasia_With_Scoliosis:pathophysiology:Golgi%20Glycosylation%20and%20Glycosaminoglycan%20Biosynthesis%20Defect","target_id":"node:disorder%3AShort_Stature_Amelogenesis_Imperfecta_And_Skeletal_Dysplasia_With_Scoliosis:pathophysiology:Cartilage%20and%20Ligament%20Proteoglycan%20Deficiency%20with%20Joint%20Instability","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[1]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"The reduced heparan sulfate content of cartilage undersupplies proteoglycan-dependent joint structures. 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Slc10a7 is transcribed in the inner dental epithelium and in ameloblasts and odontoblasts during tooth development, mutant mice have tooth enamel anomalies, and every reported affected individual has amelogenesis imperfecta, typed as hypomineralized in the founding cohort and as hypoplastic/hypomineralized in the mildest case. 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Heparan sulfate on proteoglycans is reduced roughly two-fold in patient fibroblasts and about 2.5-fold in mutant mouse cartilage, while total glycosaminoglycan content is preserved; N-glycans on plasma glycoproteins are abnormal; and O-GalNAc glycosylation is disrupted, with altered abundance of the C1GALT1 chaperone COSMC and mislocalization of the calcium-binding Golgi cargo sorter Cab45. This is the organ-agnostic substitution this entry makes against the CDG module's Golgi trigger: the module's generic disruption of Golgi glycosylation machinery is here caused by a luminal ionic lesion rather than by loss of a glycosyltransferase or of a tethering complex.","url":"https://dismech.monarchinitiative.org/pages/disorders/Short_Stature,_Amelogenesis_Imperfecta,_and_Skeletal_Dysplasia_with_Scoliosis.html#pathophysiology-golgi-glycosylation-and-glycosaminoglycan-biosynthesis-defect","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AShort_Stature_Amelogenesis_Imperfecta_And_Skeletal_Dysplasia_With_Scoliosis:pathophysiology:Growth%20Plate%20Disorganization%20and%20Impaired%20Skeletal%20Mineralization","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Growth Plate Disorganization and Impaired Skeletal Mineralization","description":"In the growth plate the consequence is architectural: mutant mice show shortened long bones with growth plate disorganization, and the human counterpart is disproportionate short stature with short long bones, small epiphyses and advanced carpal and tarsal ossification. Mineralization is reduced as well as growth: affected individuals have decreased bone mineral density compatible with osteoporosis, and knockdown zebrafish show a strong reduction in bone mineralization by alizarin red staining. This entry does not declare conformance to the defective_skeletal_mineralization module, because none of that module's three trigger arms (calciopenic, phosphopenic, mineralization-inhibitor excess) applies here — the lesion is failure to deliver the organic matrix, with normal calcium, phosphate and pyrophosphate handling as far as is reported.","url":"https://dismech.monarchinitiative.org/pages/disorders/Short_Stature,_Amelogenesis_Imperfecta,_and_Skeletal_Dysplasia_with_Scoliosis.html#pathophysiology-growth-plate-disorganization-and-impaired-skeletal-mineralization","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:2:model:kb/disorders/Short_Stature_Amelogenesis_Imperfecta_And_Skeletal_Dysplasia_With_Scoliosis.yaml:SLC10A7-CDG patient dermal fibroblasts","source_id":"model:kb/disorders/Short_Stature_Amelogenesis_Imperfecta_And_Skeletal_Dysplasia_With_Scoliosis.yaml:SLC10A7-CDG patient dermal fibroblasts","target_id":"node:disorder%3AShort_Stature_Amelogenesis_Imperfecta_And_Skeletal_Dysplasia_With_Scoliosis:pathophysiology:Defective%20Post-Golgi%20Glycoprotein%20Delivery%20to%20the%20Extracellular%20Matrix","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[2]","label":"Measures","directed":false,"relationship":"MEASURES","fidelity":"HIGH","causal_link_type":null,"causal_link_type_label":null,"description":"Glycoproteins are mislocalized intracellularly and post-Golgi transport to the cell membrane is defective.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AShort_Stature_Amelogenesis_Imperfecta_And_Skeletal_Dysplasia_With_Scoliosis:4:1","source_id":"node:disorder%3AShort_Stature_Amelogenesis_Imperfecta_And_Skeletal_Dysplasia_With_Scoliosis:pathophysiology:Defective%20Post-Golgi%20Glycoprotein%20Delivery%20to%20the%20Extracellular%20Matrix","target_id":"node:disorder%3AShort_Stature_Amelogenesis_Imperfecta_And_Skeletal_Dysplasia_With_Scoliosis:pathophysiology:Ameloblast%20Enamel%20Matrix%20Failure","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[4].downstream[1]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"The enamel organ depends on the same secretory route. This routing is an inference rather than a measurement and is the subject of the gap_enamel_route_gag_versus_trafficking discussion.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AShort_Stature_Amelogenesis_Imperfecta_And_Skeletal_Dysplasia_With_Scoliosis:4:0","source_id":"node:disorder%3AShort_Stature_Amelogenesis_Imperfecta_And_Skeletal_Dysplasia_With_Scoliosis:pathophysiology:Defective%20Post-Golgi%20Glycoprotein%20Delivery%20to%20the%20Extracellular%20Matrix","target_id":"node:disorder%3AShort_Stature_Amelogenesis_Imperfecta_And_Skeletal_Dysplasia_With_Scoliosis:pathophysiology:Growth%20Plate%20Disorganization%20and%20Impaired%20Skeletal%20Mineralization","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[4].downstream[0]","label":"Indirectly causes (unknown 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glycosaminoglycan"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:30082715","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30082715","reference_title":"SLC10A7 mutations cause a skeletal dysplasia with amelogenesis imperfecta mediated by GAG biosynthesis defects.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"we identify decreased heparan sulfate levels in Slc10a7-/- mouse cartilage and patient fibroblasts","explanation":"Establishes patient fibroblasts as a human system carrying the disease biochemistry."},{"reference":"PMID:30082715","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30082715","reference_title":"SLC10A7 mutations cause a skeletal dysplasia with amelogenesis imperfecta mediated by GAG biosynthesis defects.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"After addition of extracellular CaCl2, SLC10A7-deficient patient fibroblasts showed a significantly increased Ca2+ influx compared with control fibroblasts.","explanation":"Establishes the system as informative for the calcium node."},{"reference":"PMID:30082715","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30082715","reference_title":"SLC10A7 mutations cause a skeletal dysplasia with amelogenesis imperfecta mediated by GAG biosynthesis defects.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"the proportion of heparan sulfate (HS) was significantly reduced by ~2-fold in SLC10A7-deficient patient fibroblasts compared with control fibroblasts","explanation":"The measurement and its direction."},{"reference":"PMID:29878199","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/29878199","reference_title":"Integrating glycomics and genomics uncovers SLC10A7 as essential factor for bone mineralization by regulating post-Golgi protein transport and 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In the second cousin the corneas showed vascularised opacities with central thickened white cream-coloured tissue and a thinner greyish periphery over an epithelialised surface. Both children underwent corneal grafting; one experienced graft rejection. Screening for a storage disease — white cell inclusions, urine mucopolysaccharides and oligosaccharides — was negative, which is the standard first differential for neonatal corneal clouding.","url":"https://dismech.monarchinitiative.org/pages/disorders/Spondylometaphyseal_Dysplasia_with_Corneal_Dystrophy.html#pathophysiology-corneal-dystrophy","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ASpondylometaphyseal_Dysplasia_with_Corneal_Dystrophy:phenotype:Hypertelorism%20with%20Depressed%20Nasal%20Bridge","kind":"phenotype","kind_label":"Phenotype","label":"Hypertelorism with Depressed Nasal Bridge","description":"Hypertelorism, prominent eyes, a depressed nasal bridge, and a short upturned nose in both affected children.","url":"https://dismech.monarchinitiative.org/pages/disorders/Spondylometaphyseal_Dysplasia_with_Corneal_Dystrophy.html#phenotype-hypertelorism-with-depressed-nasal-bridge","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ASpondylometaphyseal_Dysplasia_with_Corneal_Dystrophy:phenotype:Patent%20Ductus%20Arteriosus","kind":"phenotype","kind_label":"Phenotype","label":"Patent Ductus Arteriosus","description":"A large patent ductus arteriosus in both affected children, requiring surgical correction in one and producing a left-to-right shunt in the other.","url":"https://dismech.monarchinitiative.org/pages/disorders/Spondylometaphyseal_Dysplasia_with_Corneal_Dystrophy.html#phenotype-patent-ductus-arteriosus","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ASpondylometaphyseal_Dysplasia_with_Corneal_Dystrophy:phenotype:Severe%20Developmental%20Delay","kind":"phenotype","kind_label":"Phenotype","label":"Severe Developmental Delay","description":"Severe global developmental delay. At six years the surviving proband could roll over and sit unsupported but not bear weight, was wheelchair-bound, and had no speech or meaningful babbling despite being able to hear and understand words.","url":"https://dismech.monarchinitiative.org/pages/disorders/Spondylometaphyseal_Dysplasia_with_Corneal_Dystrophy.html#phenotype-severe-developmental-delay","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ASpondylometaphyseal_Dysplasia_with_Corneal_Dystrophy:pathophysiology:Spondylometaphyseal%20Skeletal%20Dysplasia","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Spondylometaphyseal Skeletal Dysplasia","description":"Profound limb shortening involving both proximal and distal segments, with short fingers and toes and a narrow chest. Radiographs show short long bones with wide metaphyses and coarse metaphyseal trabeculae, cupping of the distal radius and ulna, uncalcified distal femoral and proximal tibial epiphyses in the neonate, short ribs with a wide anterior aspect, anterior beaking of the lumbar and thoracic vertebrae with wide intervertebral spaces, and almost square, short iliac bones with medial projections. The iliac shape was close enough to Schneckenbecken dysplasia that SLC35D1 was sequenced and excluded before the locus was mapped.","url":"https://dismech.monarchinitiative.org/pages/disorders/Spondylometaphyseal_Dysplasia_with_Corneal_Dystrophy.html#pathophysiology-spondylometaphyseal-skeletal-dysplasia","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Spondylometaphyseal_Dysplasia_with_Corneal_Dystrophy.yaml:SMDCD patient-derived dermal fibroblasts","source_id":"model:kb/disorders/Spondylometaphyseal_Dysplasia_with_Corneal_Dystrophy.yaml:SMDCD patient-derived dermal fibroblasts","target_id":"node:disorder%3ASpondylometaphyseal_Dysplasia_with_Corneal_Dystrophy:pathophysiology:F-Actin%20Cytoskeletal%20Disorganisation","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"The patient fibroblast is the only human cellular system reported for this disorder and carries both the substrate-accumulation and the cytoskeletal findings.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ASpondylometaphyseal_Dysplasia_with_Corneal_Dystrophy:2:0","source_id":"node:disorder%3ASpondylometaphyseal_Dysplasia_with_Corneal_Dystrophy:pathophysiology:Accumulation%20of%20Phosphatidylinositol%204%2C5-Bisphosphate","target_id":"node:disorder%3ASpondylometaphyseal_Dysplasia_with_Corneal_Dystrophy:pathophysiology:F-Actin%20Cytoskeletal%20Disorganisation","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Excess PIP2 disorganises the actin cytoskeleton. 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Facial morphogenesis is neural-crest-dependent and zebrafish plcb3 is expressed in neural crest, but the connection is an inference from expression rather than a demonstrated mechanism.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ASpondylometaphyseal_Dysplasia_with_Corneal_Dystrophy:3:3","source_id":"node:disorder%3ASpondylometaphyseal_Dysplasia_with_Corneal_Dystrophy:pathophysiology:F-Actin%20Cytoskeletal%20Disorganisation","target_id":"node:disorder%3ASpondylometaphyseal_Dysplasia_with_Corneal_Dystrophy:phenotype:Patent%20Ductus%20Arteriosus","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[3].downstream[3]","label":"Causes (directness unknown)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"UNKNOWN","causal_link_type_label":"Unknown","description":"A large patent ductus arteriosus occurred in both affected children. Both were also born preterm — at 29 and 27 weeks — and prematurity alone is a sufficient explanation for a persistent duct, so this edge is left with directness UNKNOWN rather than asserted as part of the syndrome.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ASpondylometaphyseal_Dysplasia_with_Corneal_Dystrophy:3:1","source_id":"node:disorder%3ASpondylometaphyseal_Dysplasia_with_Corneal_Dystrophy:pathophysiology:F-Actin%20Cytoskeletal%20Disorganisation","target_id":"node:disorder%3ASpondylometaphyseal_Dysplasia_with_Corneal_Dystrophy:phenotype:Severe%20Developmental%20Delay","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[3].downstream[1]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"Severe global developmental delay is part of the syndrome and PLCB3 is most highly expressed in brain, but no step between the phosphoinositide defect and the neurodevelopmental phenotype has been demonstrated. Prematurity and chronic respiratory failure are uncontrolled confounders in both reported children.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ASpondylometaphyseal_Dysplasia_with_Corneal_Dystrophy:3:0","source_id":"node:disorder%3ASpondylometaphyseal_Dysplasia_with_Corneal_Dystrophy:pathophysiology:F-Actin%20Cytoskeletal%20Disorganisation","target_id":"node:disorder%3ASpondylometaphyseal_Dysplasia_with_Corneal_Dystrophy:pathophysiology:Spondylometaphyseal%20Skeletal%20Dysplasia","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[3].downstream[0]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"The skeletal lesion is attributed to disturbed phosphoinositide signalling during skeletal development, supported by expression of Plcb3 in bone, cartilage, and neural crest in zebrafish and by abnormal skeletal patterning with malformed facial and thoracic bones in zebrafish plcb3 null mutants. 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This supports posttranscriptional destabilization in the tested systems; the intervening trafficking mechanism and its prevalence across human alleles remain unresolved.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Recessive_Spinocerebellar_Ataxia_20.html#pathophysiology-accelerated-spastin-turnover","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3AAutosomal_Recessive_Spinocerebellar_Ataxia_20:pathophysiology:Axonal%20Microtubule%20Disorganization","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Axonal Microtubule Disorganization","description":"Conditional Snx14-deficient mouse Purkinje axons show microtubule misalignment and swelling. 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The historical numbered AGM series does not exhaust the modern disease spectrum.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Agammaglobulinemia.html#pathophysiology-reduced-pi3k-p110-delta-function","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAutosomal_Agammaglobulinemia:pathophysiology:Reduced%20Receptor-Proximal%20B-Cell%20Signaling","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced Receptor-Proximal B-Cell Signaling","description":"Insufficient signaling through the B-cell developmental checkpoint can follow receptor-component or adaptor defects. This is a shared functional consequence, not proof that all listed genotypes have identical signaling lesions.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Agammaglobulinemia.html#pathophysiology-reduced-receptor-proximal-b-cell-signaling","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAutosomal_Agammaglobulinemia:pathophysiology:Restricted%20B-Lineage%20Chromatin%20Accessibility","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Restricted B-Lineage Chromatin Accessibility","description":"ATAC-seq in edited RS4;11 pro-B leukemia cells links reduced PU.1 dose to a less accessible B-lineage regulatory landscape. Cell-line gene-network effects support a developmental model but are not direct chromatin measurements in all patients.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Agammaglobulinemia.html#pathophysiology-restricted-b-lineage-chromatin-accessibility","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAutosomal_Agammaglobulinemia:pathophysiology:Truncated%20LRRC8A%20Protein","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Truncated LRRC8A Protein","description":"One human balanced translocation generated a truncated LRRC8A protein alongside wild-type protein. The gene-disease relationship remains Limited. Dominant interference is a hypothesis supported by a forced-expression mouse experiment, not an established universal channel mechanism.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Agammaglobulinemia.html#pathophysiology-truncated-lrrc8a-protein","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Autosomal_Agammaglobulinemia.yaml:SPI1-edited human hematopoietic progenitor differentiation","source_id":"model:kb/disorders/Autosomal_Agammaglobulinemia.yaml:SPI1-edited human hematopoietic progenitor differentiation","target_id":"node:disorder%3AAutosomal_Agammaglobulinemia:pathophysiology:Impaired%20B-Cell%20Development","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Partially Recapitulates","directed":false,"relationship":"PARTIALLY_RECAPITULATES","fidelity":"NOT_SPECIFIED","causal_link_type":null,"causal_link_type_label":null,"description":"SPI1 editing impairs early B-cell and myeloid differentiation in culture.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AAutosomal_Agammaglobulinemia:9:0","source_id":"node:disorder%3AAutosomal_Agammaglobulinemia:pathophysiology:Defective%20TCF3%20Transcription-Factor%20Activity","target_id":"node:disorder%3AAutosomal_Agammaglobulinemia:pathophysiology:Impaired%20B-Cell%20Development","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[9].downstream[0]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"Reduced or interfering transcription-factor activity impairs B-lineage output. The particular transcriptional targets that mediate each human phenotype are unresolved.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AAutosomal_Agammaglobulinemia:13:2","source_id":"node:disorder%3AAutosomal_Agammaglobulinemia:pathophysiology:FNIP1%20Protein%20Deficiency","target_id":"node:disorder%3AAutosomal_Agammaglobulinemia:pathophysiology:Impaired%20B-Cell%20Development","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[13].downstream[2]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"Human deficiency is associated with impaired B-lineage output, without a discrete universal arrest or an experimentally isolated metabolic mediator.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AAutosomal_Agammaglobulinemia:16:0","source_id":"node:disorder%3AAutosomal_Agammaglobulinemia:pathophysiology:Impaired%20B-Cell%20Development","target_id":"node:disorder%3AAutosomal_Agammaglobulinemia:pathophysiology:Reduced%20Circulating%20B-Cell%20Output","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[16].downstream[0]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"Impaired differentiation and survival reduce mature B-cell output, with residual cells and evolving depletion in some alleles.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AAutosomal_Agammaglobulinemia:15:0","source_id":"node:disorder%3AAutosomal_Agammaglobulinemia:pathophysiology:Impaired%20TOP2B%20Activity","target_id":"node:disorder%3AAutosomal_Agammaglobulinemia:pathophysiology:Impaired%20B-Cell%20Development","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[15].downstream[0]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"Mouse conditional and disease-allele models impair multiple B-cell stages. DNA topology, damage and transcriptional programs are candidate mediators rather than a single proven human pathway.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AAutosomal_Agammaglobulinemia:7:0","source_id":"node:disorder%3AAutosomal_Agammaglobulinemia:pathophysiology:Loss%20of%20PI3K%20p85-Alpha","target_id":"node:disorder%3AAutosomal_Agammaglobulinemia:pathophysiology:Impaired%20B-Cell%20Development","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[7].downstream[0]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"The homozygous patient had very few early B-lineage cells. The precise lineage-specific pathway from p85-alpha loss remains incompletely resolved.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AAutosomal_Agammaglobulinemia:8:0","source_id":"node:disorder%3AAutosomal_Agammaglobulinemia:pathophysiology:Reduced%20PI3K%20p110-Delta%20Function","target_id":"node:disorder%3AAutosomal_Agammaglobulinemia:pathophysiology:Impaired%20B-Cell%20Development","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[8].downstream[0]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"Recessive catalytic-subunit deficiency is associated with reduced B-cell output; the cited synthesis does not isolate one universal developmental stage or each downstream signal.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AAutosomal_Agammaglobulinemia:6:0","source_id":"node:disorder%3AAutosomal_Agammaglobulinemia:pathophysiology:Reduced%20Receptor-Proximal%20B-Cell%20Signaling","target_id":"node:disorder%3AAutosomal_Agammaglobulinemia:pathophysiology:Impaired%20B-Cell%20Development","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[6].downstream[0]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"Receptor/adaptor defects reduce developmental progression; the original BLNK patient had pro-B cells without detected pre-B or mature B cells.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AAutosomal_Agammaglobulinemia:11:0","source_id":"node:disorder%3AAutosomal_Agammaglobulinemia:pathophysiology:Restricted%20B-Lineage%20Chromatin%20Accessibility","target_id":"node:disorder%3AAutosomal_Agammaglobulinemia:pathophysiology:Impaired%20B-Cell%20Development","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[11].downstream[0]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"Chromatin restriction is proposed to constrain the transcriptional program needed for B-cell progression. Patient phenotype and edited HSPC experiments support the model without proving every intervening regulatory target.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":2},{"id":"causal:disorder%3AAutosomal_Agammaglobulinemia:14:0","source_id":"node:disorder%3AAutosomal_Agammaglobulinemia:pathophysiology:Truncated%20LRRC8A%20Protein","target_id":"node:disorder%3AAutosomal_Agammaglobulinemia:pathophysiology:Impaired%20B-Cell%20Development","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[14].downstream[0]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"The single human association and experimental mutant expression support a provisional link; the relevant molecular intermediates and replication in additional families remain unresolved.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1}]}}],"mechanism_names":["Impaired B-Cell Development"],"relationships":["Partially Recapitulates"],"fidelities":["Not Specified"],"biological_scales":["Cellular"],"system_context_sources":["Linked mechanism anatomy","Linked mechanism cell type","Linked mechanism biological scale"],"modeled_system_labels":["bone marrow","B cell","Cellular"],"biological_process_terms":[{"id":"GO:0030183","label":"B cell differentiation","display_label":"B cell differentiation","url":"http://purl.obolibrary.org/obo/GO_0030183"}],"biological_processes":["B cell differentiation"],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":["B-lineage differentiation output"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:33951726","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33951726","reference_title":"Constrained chromatin accessibility in PU.1-mutated agammaglobulinemia patients.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Introducing disease-similar SPI1 mutations into human hematopoietic stem and progenitor cells impaired early in vitro B cell and myeloid cell differentiation.","explanation":"Edited cord-blood progenitors carry mixtures of near-variant indels, not precise patient-allele knock-ins; lineage selection supports but does not isolate the chromatin mediator."}],"evidence_text":["Introducing disease-similar SPI1 mutations into human hematopoietic stem and progenitor cells impaired early in vitro B cell and myeloid cell differentiation.","Edited cord-blood progenitors carry mixtures of near-variant indels, not precise patient-allele knock-ins; lineage selection supports but does not isolate the chromatin mediator."],"evidence_status":"Evidence recorded","metadata_completeness":70,"metadata_present":["Model category","Anatomy","Cell type","Cell source","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Organism","Culture system"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Autosomal_Agammaglobulinemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autosomal_Agammaglobulinemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Agammaglobulinemia.html#experimental-model-spi1-edited-human-hematopoietic-progenitor-differentiation","source_anchor":"experimental-model-spi1-edited-human-hematopoietic-progenitor-differentiation"},{"id":"model:kb/disorders/Persistent_Truncus_Arteriosus.yaml:Splotch mutant mouse","name":"Splotch mutant mouse","description":"The founding genetic model, and the experiment that established the cardiac neural crest as the tissue of origin for this malformation. 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The model dies mid-gestation, so it cannot address postnatal physiology at all.\n","notes":null,"context_id":"disorder:Persistent_Truncus_Arteriosus","context_kind":"Disorder","disease_name":"Persistent Truncus Arteriosus","disease_synonyms":["Truncus arteriosus communis","Common arterial trunk","Truncus arteriosus"],"disease_term":{"id":"MONDO:0018072","label":"persistent truncus arteriosus","display_label":"persistent truncus arteriosus","url":"http://purl.obolibrary.org/obo/MONDO_0018072"},"experimental_model_type":"OTHER","experimental_model_type_label":"Other","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"house mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"},"organism_label":"Mus musculus","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[{"id":"UBERON:0004145","label":"outflow tract","display_label":"Outflow tract","url":"http://purl.obolibrary.org/obo/UBERON_0004145"},{"id":"UBERON:0002061","label":"truncus arteriosus","display_label":"Truncus arteriosus","url":"http://purl.obolibrary.org/obo/UBERON_0002061"},{"id":"UBERON:0004142","label":"outflow tract septum","display_label":"Outflow tract septum","url":"http://purl.obolibrary.org/obo/UBERON_0004142"}],"linked_anatomy_labels":["outflow tract","truncus arteriosus","outflow tract septum"],"anatomy":[{"id":"UBERON:0004145","label":"outflow tract","display_label":"Outflow tract","url":"http://purl.obolibrary.org/obo/UBERON_0004145"},{"id":"UBERON:0002061","label":"truncus arteriosus","display_label":"Truncus arteriosus","url":"http://purl.obolibrary.org/obo/UBERON_0002061"},{"id":"UBERON:0004142","label":"outflow tract septum","display_label":"Outflow tract septum","url":"http://purl.obolibrary.org/obo/UBERON_0004142"}],"anatomy_labels":["outflow tract","truncus arteriosus","outflow tract septum"],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[{"id":"CL:0011012","label":"neural crest cell","display_label":"Cardiac neural crest cell","url":"http://purl.obolibrary.org/obo/CL_0011012"}],"linked_cell_type_labels":["neural crest cell"],"cell_types":[{"id":"CL:0011012","label":"neural crest cell","display_label":"Cardiac neural crest cell","url":"http://purl.obolibrary.org/obo/CL_0011012"}],"cell_type_labels":["neural crest cell"],"conditions":[],"cell_source":null,"source_category":null,"culture_system":null,"publication":"PMID:2619088","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/2619088","mechanisms":[{"target":"Cardiac neural crest and second heart field program disruption","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Persistent_Truncus_Arteriosus.html#pathophysiology-cardiac-neural-crest-and-second-heart-field-program-disruption","relationship":"NOT_SPECIFIED","relationship_label":"Not Specified","fidelity":"NOT_SPECIFIED","fidelity_label":"Not Specified","description":"Splotch disrupts neural-crest-derived cell populations, which is the trigger node here.\n","limitations":null,"biological_scale":"CELLULAR","anatomy":[{"id":"UBERON:0004145","label":"outflow tract","display_label":"Outflow tract","url":"http://purl.obolibrary.org/obo/UBERON_0004145"}],"cell_types":[{"id":"CL:0011012","label":"neural crest cell","display_label":"Cardiac neural crest cell","url":"http://purl.obolibrary.org/obo/CL_0011012"}],"biological_processes":[{"id":"GO:0061309","label":"cardiac neural crest cell development involved in outflow tract morphogenesis","display_label":"cardiac neural crest cell development involved in outflow tract morphogenesis","url":"http://purl.obolibrary.org/obo/GO_0061309"},{"id":"GO:0001755","label":"neural crest cell migration","display_label":"neural crest cell migration","url":"http://purl.obolibrary.org/obo/GO_0001755"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[],"evidence":[],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Persistent_Truncus_Arteriosus","model_node_id":"model:kb/disorders/Persistent_Truncus_Arteriosus.yaml:Splotch mutant mouse","focus_node_id":"node:disorder%3APersistent_Truncus_Arteriosus:pathophysiology:Cardiac%20neural%20crest%20and%20second%20heart%20field%20program%20disruption","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Persistent_Truncus_Arteriosus.html#pathograph","nodes":[{"id":"model:kb/disorders/Persistent_Truncus_Arteriosus.yaml:Splotch mutant mouse","kind":"experimental_model","kind_label":"NAM model","label":"Splotch mutant mouse","description":"The founding genetic model, and the experiment that established the cardiac neural crest as the tissue of origin for this malformation. 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The model dies mid-gestation, so it cannot address postnatal physiology at all.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Persistent_Truncus_Arteriosus.html#experimental-model-splotch-mutant-mouse","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APersistent_Truncus_Arteriosus:pathophysiology:Cardiac%20neural%20crest%20and%20second%20heart%20field%20program%20disruption","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Cardiac neural crest and second heart field program disruption","description":"The outflow tract is built by two cell populations acting together: cardiac neural crest cells migrating through pharyngeal arches three, four, and six to form the elastogenic smooth muscle of the aorticopulmonary septum, and second heart field mesoderm adding myocardium to the elongating outflow tract. 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That is why the ventricular septal defect here is not an independent second lesion but part of the same failure.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Persistent_Truncus_Arteriosus.html#pathophysiology-failure-of-aorticopulmonary-septation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Persistent_Truncus_Arteriosus.yaml:Splotch mutant mouse","source_id":"model:kb/disorders/Persistent_Truncus_Arteriosus.yaml:Splotch mutant mouse","target_id":"node:disorder%3APersistent_Truncus_Arteriosus:pathophysiology:Cardiac%20neural%20crest%20and%20second%20heart%20field%20program%20disruption","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Not Specified","directed":false,"relationship":"NOT_SPECIFIED","fidelity":"NOT_SPECIFIED","causal_link_type":null,"causal_link_type_label":null,"description":"Splotch disrupts neural-crest-derived cell populations, which is the trigger node here.\n","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3APersistent_Truncus_Arteriosus:0:0","source_id":"node:disorder%3APersistent_Truncus_Arteriosus:pathophysiology:Cardiac%20neural%20crest%20and%20second%20heart%20field%20program%20disruption","target_id":"node:disorder%3APersistent_Truncus_Arteriosus:pathophysiology:Failure%20of%20aorticopulmonary%20septation","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Without a properly specified and positioned neural-crest-derived septal population, the conotruncal ridges do not fuse and no aorticopulmonary septum forms.\n","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1}]}},{"target":"Failure of aorticopulmonary septation","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Persistent_Truncus_Arteriosus.html#pathophysiology-failure-of-aorticopulmonary-septation","relationship":"NOT_SPECIFIED","relationship_label":"Not Specified","fidelity":"NOT_SPECIFIED","fidelity_label":"Not Specified","description":"The mutant reproduces the septation failure itself.\n","limitations":null,"biological_scale":"TISSUE","anatomy":[{"id":"UBERON:0002061","label":"truncus arteriosus","display_label":"Truncus arteriosus","url":"http://purl.obolibrary.org/obo/UBERON_0002061"},{"id":"UBERON:0004142","label":"outflow tract septum","display_label":"Outflow tract septum","url":"http://purl.obolibrary.org/obo/UBERON_0004142"}],"cell_types":[],"biological_processes":[{"id":"GO:0003148","label":"outflow tract septum morphogenesis","display_label":"outflow tract septum morphogenesis","url":"http://purl.obolibrary.org/obo/GO_0003148"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[],"evidence":[],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Persistent_Truncus_Arteriosus","model_node_id":"model:kb/disorders/Persistent_Truncus_Arteriosus.yaml:Splotch mutant mouse","focus_node_id":"node:disorder%3APersistent_Truncus_Arteriosus:pathophysiology:Failure%20of%20aorticopulmonary%20septation","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Persistent_Truncus_Arteriosus.html#pathograph","nodes":[{"id":"model:kb/disorders/Persistent_Truncus_Arteriosus.yaml:Splotch mutant mouse","kind":"experimental_model","kind_label":"NAM model","label":"Splotch mutant mouse","description":"The founding genetic model, and the experiment that established the cardiac neural crest as the tissue of origin for this malformation. 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The model dies mid-gestation, so it cannot address postnatal physiology at all.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Persistent_Truncus_Arteriosus.html#experimental-model-splotch-mutant-mouse","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APersistent_Truncus_Arteriosus:pathophysiology:Failure%20of%20aorticopulmonary%20septation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Failure of aorticopulmonary septation","description":"The defining embryologic event, occurring in weeks five to eight of human gestation. The conotruncal ridges fail to fuse and spiral, so no aorticopulmonary septum divides the common trunk into aorta and pulmonary trunk. 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That is why the ventricular septal defect here is not an independent second lesion but part of the same failure.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Persistent_Truncus_Arteriosus.html#pathophysiology-failure-of-aorticopulmonary-septation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APersistent_Truncus_Arteriosus:pathophysiology:Cardiac%20neural%20crest%20and%20second%20heart%20field%20program%20disruption","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Cardiac neural crest and second heart field program disruption","description":"The outflow tract is built by two cell populations acting together: cardiac neural crest cells migrating through pharyngeal arches three, four, and six to form the elastogenic smooth muscle of the aorticopulmonary septum, and second heart field mesoderm adding myocardium to the elongating outflow tract. 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Because both ventricles eject into it across a large non-restrictive ventricular septal defect, systemic and pulmonary venous return mix obligatorily at the trunk, and both ventricles see systemic pressure.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Persistent_Truncus_Arteriosus.html#pathophysiology-single-arterial-trunk-overriding-a-ventricular-septal-defect","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:1:model:kb/disorders/Persistent_Truncus_Arteriosus.yaml:Splotch mutant mouse","source_id":"model:kb/disorders/Persistent_Truncus_Arteriosus.yaml:Splotch mutant 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involvement that parallels the 22q11.2 phenotype in humans and supports a shared pharyngeal and neural-crest origin."}],"evidence_text":["It is shown that in homozygous mutant embryos, the septation of the truncus arteriosus does not proceed normally, resulting in persistent truncus arteriosus.","These results provide indirect evidence, that cells contributing to the aortic arches and the septum of the truncus arteriosus in mice are derived from the neural crest.","The development of the thymus, the parathyroid and the ultimobranchial bodies are also variably affected in mutants.","Direct recapitulation of the human malformation from a neural crest defect.","The inference that makes this model mechanistically informative rather than merely phenocopying, and the basis for the trigger node in this entry.","The extracardiac involvement that parallels the 22q11.2 phenotype in humans and supports a shared pharyngeal and neural-crest origin."],"evidence_status":"Evidence 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So a curator or laboratory reading a novel SRCAP truncation should ask where it sits before predicting which disease it causes, and should not treat DEHMBA as a milder or severer FLHS.","url":"https://dismech.monarchinitiative.org/pages/disorders/Developmental_Delay,_Hypotonia,_Musculoskeletal_Defects,_and_Behavioral_Abnormalities.html#pathophysiology-srcap-loss-of-function-allele-outside-the-flhs-hotspot","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ADevelopmental_Delay_Hypotonia_Musculoskeletal_Defects_And_Behavioral_Abnormalities:pathophysiology:SRCAP%20Complex%20Haploinsufficiency","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"SRCAP Complex Haploinsufficiency","description":"Reduced SRCAP dosage leaves the SRCAP chromatin-remodelling complex - the human counterpart of yeast SWR1 - operating below its normal capacity. 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Examples: HepG2, A549, Caco-2, etc.","namo_docs_url":"https://monarch-initiative.github.io/namo/elements/CellLineModel/","namo_ontology_url":"https://w3id.org/monarch-initiative/namo/CellLineModel","namo_mapping_basis":"Safe mapping from DisMech category","namo_class_in_schema":true,"namo_schema_status":"Defined in NAMO schema used for this build","modality":"Cellular system","organism":{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"},"organism_label":"Mus musculus","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[{"id":"CL:0002322","label":"embryonic stem cell","display_label":"embryonic stem cell","url":"http://purl.obolibrary.org/obo/CL_0002322"}],"model_cell_type_labels":["embryonic stem cell"],"linked_cell_types":[{"id":"CL:0002322","label":"embryonic stem cell","display_label":"embryonic stem cell","url":"http://purl.obolibrary.org/obo/CL_0002322"}],"linked_cell_type_labels":["embryonic stem cell"],"cell_types":[{"id":"CL:0002322","label":"embryonic stem cell","display_label":"embryonic stem cell","url":"http://purl.obolibrary.org/obo/CL_0002322"}],"cell_type_labels":["embryonic stem cell"],"conditions":[],"cell_source":null,"source_category":"Immortalized / cell line","culture_system":null,"publication":"PMID:38656788","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38656788","mechanisms":[{"target":"Loss of Stemness and Altered Lineage Commitment","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Intellectual_Developmental_Disorder,_Autosomal_Dominant_72.html#pathophysiology-loss-of-stemness-and-altered-lineage-commitment","relationship":"RECAPITULATES","relationship_label":"Recapitulates","fidelity":"MODERATE","fidelity_label":"Moderate","description":"Directly demonstrates the stemness and lineage-commitment consequences of heterozygous Srrm2 loss at the same allelic dosage as human disease.","limitations":"Mouse embryonic stem cells in culture, not human tissue; the link between early-embryonic stemness defects and the postnatal MRD72 phenotype is inferred rather than shown.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[{"id":"CL:0002322","label":"embryonic stem cell","display_label":"embryonic stem cell","url":"http://purl.obolibrary.org/obo/CL_0002322"}],"biological_processes":[{"id":"GO:0019827","label":"stem cell population maintenance","display_label":"stem cell population maintenance","url":"http://purl.obolibrary.org/obo/GO_0019827"},{"id":"GO:0030154","label":"cell differentiation","display_label":"cell differentiation","url":"http://purl.obolibrary.org/obo/GO_0030154"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[],"evidence":[{"reference":"PMID:38656788","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38656788","reference_title":"SRRM2 splicing factor modulates cell fate in early development.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"we show that Srrm2 dosage is critical for maintaining embryonic stem cell pluripotency and cell identity","explanation":"States the dosage-dependent stemness finding this model establishes."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Intellectual_Developmental_Disorder_Autosomal_Dominant_72","model_node_id":"model:kb/disorders/Intellectual_Developmental_Disorder_Autosomal_Dominant_72.yaml:Srrm2 heterozygous mouse embryonic stem cells","focus_node_id":"node:disorder%3AIntellectual_Developmental_Disorder_Autosomal_Dominant_72:pathophysiology:Loss%20of%20Stemness%20and%20Altered%20Lineage%20Commitment","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Intellectual_Developmental_Disorder,_Autosomal_Dominant_72.html#pathograph","nodes":[{"id":"model:kb/disorders/Intellectual_Developmental_Disorder_Autosomal_Dominant_72.yaml:Srrm2 heterozygous mouse embryonic stem cells","kind":"experimental_model","kind_label":"NAM model","label":"Srrm2 heterozygous mouse embryonic stem cells","description":"Constitutively Srrm2-heterozygous mouse embryonic stem cells, plus transient RNA-interference depletion, used to dissect the earliest consequences of reduced Srrm2 dosage. 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We also report for the first time an impairment of migration in TCOF1+/- NC and mesenchymal stem cells.","explanation":"The finding is stated directly in the model paper."}]}],"findings_text":["TCOF1+/- human neural crest cells recapitulate the abnormal cell-death phenotype of the murine TCS model and add a migration deficit."],"evidence":[{"reference":"PMID:30375284","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30375284","reference_title":"A Novel Human Pluripotent Stem Cell-Derived Neural Crest Model of Treacher Collins Syndrome Shows Defects in Cell Death and Migration.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We assessed the potential of the derived NC population to model the neurocristopathy, Treacher Collins Syndrome (TCS), using small interfering RNA (siRNA) knockdown of TCOF1 and by creating different TCOF1+/- HPSC lines through CRISPR/Cas9 technology.","explanation":"The primary study describes both perturbation strategies used to construct the human model."},{"reference":"PMID:30375284","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30375284","reference_title":"A Novel Human Pluripotent Stem Cell-Derived Neural Crest Model of Treacher Collins Syndrome Shows Defects in Cell Death and Migration.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We also report for the first time an impairment of migration in TCOF1+/- NC and mesenchymal stem cells.","explanation":"The modeled mechanism is directly measured in the engineered human cells."},{"reference":"PMID:30375284","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30375284","reference_title":"A Novel Human Pluripotent Stem Cell-Derived Neural Crest Model of Treacher Collins Syndrome Shows Defects in Cell Death and Migration.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The NC cells derived from TCOF1+/- HPSC recapitulate the phenotype of the reported TCS murine model. We also report for the first time an impairment of migration in TCOF1+/- NC and mesenchymal stem cells.","explanation":"The finding is stated directly in the model paper."}],"evidence_text":["We assessed the potential of the derived NC population to model the neurocristopathy, Treacher Collins Syndrome (TCS), using small interfering RNA (siRNA) knockdown of TCOF1 and by creating different TCOF1+/- HPSC lines through CRISPR/Cas9 technology.","We also report for the first time an impairment of migration in TCOF1+/- NC and mesenchymal stem cells.","The NC cells derived from TCOF1+/- HPSC recapitulate the phenotype of the reported TCS murine model. We also report for the first time an impairment of migration in TCOF1+/- NC and mesenchymal stem cells.","The primary study describes both perturbation strategies used to construct the human model.","The modeled mechanism is directly measured in the engineered human cells.","The finding is stated directly in the model paper."],"evidence_status":"Evidence recorded","metadata_completeness":90,"metadata_present":["Model category","Organism","Anatomy","Cell type","Cell source","Culture system","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class"],"dataset_context":"Available in same entry","context_dataset_ids":["dataset:geo:gse10167","dataset:geo:gse89420"],"candidate_dataset_ids":[],"source_path":"kb/disorders/Treacher_Collins_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Treacher_Collins_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Treacher_Collins_Syndrome.html#experimental-model-tcof1-haploinsufficient-human-pluripotent-stem-cell-derived-neural-crest-model","source_anchor":"experimental-model-tcof1-haploinsufficient-human-pluripotent-stem-cell-derived-neural-crest-model"},{"id":"model:kb/disorders/Thanatophoric_Dysplasia_Type_2.yaml:TD1 and ACH iPSC-derived chondrocytes (statin rescue)","name":"TD1 and ACH iPSC-derived chondrocytes (statin rescue)","description":"Patient-specific iPSCs from thanatophoric dysplasia type I and achondroplasia patients were differentiated into chondrocytes, recapitulating degraded cartilage formation. 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This model was used to identify statins as candidate therapeutic agents that rescue the cartilage phenotype.\n","notes":null,"context_id":"disorder:Thanatophoric_Dysplasia_Type_1","context_kind":"Disorder","disease_name":"Thanatophoric Dysplasia Type 1","disease_synonyms":[],"disease_term":{"id":"MONDO:0008546","label":"thanatophoric dysplasia type 1","display_label":"thanatophoric dysplasia type 1","url":"http://purl.obolibrary.org/obo/MONDO_0008546"},"experimental_model_type":null,"experimental_model_type_label":null,"namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},"organism_label":"Homo sapiens","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":"iPSC-derived","source_category":"iPSC-derived","culture_system":null,"publication":null,"publication_url":null,"mechanisms":[],"mechanism_names":[],"relationships":[],"fidelities":[],"biological_scales":[],"system_context_sources":[],"modeled_system_labels":[],"biological_process_terms":[],"biological_processes":[],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":[],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:25231866","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/25231866","reference_title":"Statin treatment rescues FGFR3 skeletal dysplasia phenotypes.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We converted fibroblasts from thanatophoric dysplasia type I (TD1) and ACH patients into iPSCs. The chondrogenic differentiation of TD1 iPSCs and ACH iPSCs resulted in the formation of degraded cartilage. We found that statins could correct the degraded cartilage in both chondrogenically differentiated TD1 and ACH iPSCs.","explanation":"First human cell-based disease model for TD1 using patient-derived iPSCs, demonstrating that TD1 chondrogenic defects are cell-autonomous and identifying statins as potential therapeutic agents."}],"evidence_text":["We converted fibroblasts from thanatophoric dysplasia type I (TD1) and ACH patients into iPSCs. The chondrogenic differentiation of TD1 iPSCs and ACH iPSCs resulted in the formation of degraded cartilage. We found that statins could correct the degraded cartilage in both chondrogenically differentiated TD1 and ACH iPSCs.","First human cell-based disease model for TD1 using patient-derived iPSCs, demonstrating that TD1 chondrogenic defects are cell-autonomous and identifying statins as potential therapeutic agents."],"evidence_status":"Evidence recorded","metadata_completeness":30,"metadata_present":["Organism","Cell source","Evidence"],"metadata_missing":["Model category","NAMO class","Anatomy","Cell type","Culture system","Modeled mechanism","Publication"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Thanatophoric_Dysplasia_Type_1.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Thanatophoric_Dysplasia_Type_1.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Thanatophoric_Dysplasia_Type_1.html#experimental-model-td1-patient-derived-ipsc-chondrogenic-model","source_anchor":"experimental-model-td1-patient-derived-ipsc-chondrogenic-model"},{"id":"model:kb/disorders/Autosomal_Recessive_Spinocerebellar_Ataxia_16.yaml:Temperature-dependent CHIP missense-variant assays","name":"Temperature-dependent CHIP missense-variant assays","description":"Recombinant proteins were assessed for HSP70 ubiquitination, chaperone-peptide binding, free ubiquitin-chain formation, thermal stability and oligomerization; transfected HEK293 cells supplied a separate protein-abundance readout. 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The study compared physiological and lower assay temperatures.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Recessive_Spinocerebellar_Ataxia_16.html#experimental-model-temperature-dependent-chip-missense-variant-assays","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAutosomal_Recessive_Spinocerebellar_Ataxia_16:pathophysiology:CHIP%20Structural%20Destabilization","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"CHIP Structural Destabilization","description":"Many tested SCAR16 variants reduce CHIP thermal stability. The p.Thr246Met U-box is structurally disorganized, whereas p.Asn65Ser has increased alpha-helical content and resistance to limited proteolysis in the 2017 study. Effects vary with allele, assay and construct; several 2017 structural experiments used an MBP fusion. Reduced steady-state abundance in cells is a distinct accompanying observation, not proof that every allele is equally unstable.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Recessive_Spinocerebellar_Ataxia_16.html#pathophysiology-chip-structural-destabilization","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAutosomal_Recessive_Spinocerebellar_Ataxia_16:pathophysiology:Biallelic%20STUB1%20Loss-of-Function%20Variants","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Biallelic STUB1 Loss-of-Function Variants","description":"Homozygous or compound heterozygous pathogenic variants in STUB1 are the initiating lesion. 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The experiments do not isolate oligomerization as the cause of a particular downstream patient phenotype.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Recessive_Spinocerebellar_Ataxia_16.html#pathophysiology-chip-oligomerization","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAutosomal_Recessive_Spinocerebellar_Ataxia_16:pathophysiology:Loss%20of%20CHIP%20E3%20Ubiquitin%20Ligase%20Activity","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Loss of CHIP E3 Ubiquitin Ligase Activity","description":"Loss or reduction of ubiquitin ligase activity is allele- and assay-dependent. p.Thr246Met abolishes Hsc70- and self-ubiquitination while retaining chaperone interactions, but also destabilizes and oligomerizes CHIP. 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so the arm remains an in vitro inference about human disease.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[{"id":"CL:0000359","label":"vascular associated smooth muscle cell","display_label":"second heart field-derived smooth muscle cell","url":"http://purl.obolibrary.org/obo/CL_0000359"}],"biological_processes":[{"id":"GO:0051145","label":"smooth muscle cell differentiation","display_label":"smooth muscle cell differentiation","url":"http://purl.obolibrary.org/obo/GO_0051145"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Mechanical competence of engineered SMC tissue rings","description":null,"target":"Impaired Aortic Root Smooth Muscle Cell Differentiation","direction":"RESTORED","interpretation":"The TGFB2G276R/+ mechanical defect was reversed by TGFB2 supplementation or genetic correction, establishing that the deficit is TGFB2 dose dependent and reversible in this system.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:40139558","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40139558","reference_title":"TGFBR3 dependent mechanism of TGFB2 in smooth muscle cell differentiation and implications for TGFB2-related aortic aneurysm.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"a missense TGFB2 variant (TGFB2G276R/+) caused mechanical defects in SMC tissue ring constructs that were rescued by TGFB2 supplementation or genetic correction","explanation":"Reports the rescue measurement underlying this readout."}],"notes":null}],"evidence":[{"reference":"PMID:40139558","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40139558","reference_title":"TGFBR3 dependent mechanism of TGFB2 in smooth muscle cell differentiation and implications for TGFB2-related aortic aneurysm.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"TGFBR3KO/KO prevented the molecular rescue of TGFB2KO/+ by TGFB2 supplementation indicating the involvement of TGFBR3 in TGFB2-mediated SMC differentiation","explanation":"The epistasis result that makes this model informative for the TGFBR3-dependent differentiation node."},{"reference":"PMID:40139558","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40139558","reference_title":"TGFBR3 dependent mechanism of TGFB2 in smooth muscle cell differentiation and implications for TGFB2-related aortic aneurysm.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"a missense TGFB2 variant (TGFB2G276R/+) caused mechanical defects in SMC tissue ring constructs that were rescued by TGFB2 supplementation or genetic correction","explanation":"Reports the rescue measurement underlying this readout."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Loeys-Dietz_Syndrome_4","model_node_id":"model:kb/disorders/Loeys-Dietz_Syndrome_4.yaml:TGFB2-KO/+ human iPSC-derived smooth muscle cells and 3D tissue rings","focus_node_id":"node:disorder%3ALoeys-Dietz_Syndrome_4:pathophysiology:Impaired%20Aortic%20Root%20Smooth%20Muscle%20Cell%20Differentiation","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Loeys-Dietz_Syndrome_4.html#pathograph","nodes":[{"id":"model:kb/disorders/Loeys-Dietz_Syndrome_4.yaml:TGFB2-KO/+ human iPSC-derived smooth muscle cells and 3D tissue rings","kind":"experimental_model","kind_label":"NAM model","label":"TGFB2-KO/+ human iPSC-derived smooth muscle cells and 3D tissue rings","description":"A human, non-animal model of the LDS4 genotype: CRISPR/Cas9-engineered TGFB2KO/+ and TGFB2G276R/+ human iPSC lines differentiated to smooth muscle cells and assembled into three-dimensional tissue ring constructs, alongside TGFBR3KO/KO lines for epistasis. It supplies the mechanistic arm that patient tissue cannot - controlled genotype, isogenic comparison, and a rescue arm (TGFB2 supplementation or genetic correction).","url":"https://dismech.monarchinitiative.org/pages/disorders/Loeys-Dietz_Syndrome_4.html#experimental-model-tgfb2-ko-human-ipsc-derived-smooth-muscle-cells-and-3d-tissue-rings","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALoeys-Dietz_Syndrome_4:pathophysiology:Impaired%20Aortic%20Root%20Smooth%20Muscle%20Cell%20Differentiation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Aortic Root Smooth Muscle Cell Differentiation","description":"A developmental arm that helps explain why the aneurysm in LDS4 is concentrated at the aortic root. In human iPSC-derived smooth muscle cells, TGFB2 signals distinctively through TGFBR3 (betaglycan) rather than only the canonical type I/II receptors, and both TGFB2 and TGFBR3 are enriched in the tunica media of the aortic root specifically. TGFB2 haploinsufficiency and TGFB2 neutralisation impair differentiation of second heart field-derived smooth muscle cells - the lineage that populates the root - and a missense TGFB2 variant produced measurable mechanical defects in engineered smooth muscle tissue rings that were rescued by adding back TGFB2. This arm is grounded entirely in an in vitro human system; it complements rather than replaces the paradoxical-signalling arm.","url":"https://dismech.monarchinitiative.org/pages/disorders/Loeys-Dietz_Syndrome_4.html#pathophysiology-impaired-aortic-root-smooth-muscle-cell-differentiation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALoeys-Dietz_Syndrome_4:pathophysiology:Aortic%20Medial%20Degeneration","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Aortic Medial Degeneration","description":"The histological lesion of LDS4 is the medial degeneration common to the heritable aortopathies: fragmentation and loss of elastic fibres in the tunica media with accumulation of proteoglycans, described in both of the 2012 defining cohorts and independently as cystic medial necrosis in a dissected LDS4 aorta. The result is a media that has lost its recoil and tensile competence.","url":"https://dismech.monarchinitiative.org/pages/disorders/Loeys-Dietz_Syndrome_4.html#pathophysiology-aortic-medial-degeneration","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ALoeys-Dietz_Syndrome_4:pathophysiology:Reduced%20TGF-beta%202%20Ligand%20Availability","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced TGF-beta 2 Ligand Availability","description":"The proximal biochemical consequence of a TGFB2 loss-of-function allele is reduced cellular TGF-beta 2 proprotein and mature ligand. In smooth muscle cells and dermal fibroblasts from affected family members, TGFB2 transcript levels were comparable to control but TGF-beta 2 proprotein was reduced and no truncated protein was detectable. Crucially, this reduction is measured in peripheral cells and is the opposite of what the diseased aorta shows, which is what sets up the disorder's central paradox.","url":"https://dismech.monarchinitiative.org/pages/disorders/Loeys-Dietz_Syndrome_4.html#pathophysiology-reduced-tgf-beta-2-ligand-availability","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Loeys-Dietz_Syndrome_4.yaml:TGFB2-KO/+ human iPSC-derived smooth muscle cells and 3D tissue rings","source_id":"model:kb/disorders/Loeys-Dietz_Syndrome_4.yaml:TGFB2-KO/+ human iPSC-derived smooth muscle cells and 3D tissue 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profiling and protein stability testing.","notes":null,"context_id":"disorder:Torsion_Dystonia_6","context_kind":"Disorder","disease_name":"Torsion Dystonia 6","disease_synonyms":["DYT6","DYT6 dystonia","DYT-THAP1","THAP1 dystonia","dystonia 6, torsion","primary torsion dystonia, mixed type"],"disease_term":{"id":"MONDO:0011264","label":"torsion dystonia 6","display_label":"torsion dystonia 6","url":"http://purl.obolibrary.org/obo/MONDO_0011264"},"experimental_model_type":"CELL_LINE","experimental_model_type_label":"Cell line","namo_type":"namo:CellLineModel","declared_namo_class_name":null,"namo_class_name":"CellLineModel","namo_class_label":"Cell Line Model","namo_description":"A model system based on immortalized cell lines that can be maintained in culture indefinitely. Examples: HepG2, A549, Caco-2, etc.","namo_docs_url":"https://monarch-initiative.github.io/namo/elements/CellLineModel/","namo_ontology_url":"https://w3id.org/monarch-initiative/namo/CellLineModel","namo_mapping_basis":"Safe mapping from DisMech category","namo_class_in_schema":true,"namo_schema_status":"Defined in NAMO schema used for this build","modality":"Cellular system","organism":{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},"organism_label":"Homo sapiens","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":null,"source_category":"Immortalized / cell line","culture_system":null,"publication":"PMID:32112337","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32112337","mechanisms":[{"target":"Reduced THAP1 Transcriptional Regulatory Function","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Torsion_Dystonia_6.html#pathophysiology-reduced-thap1-transcriptional-regulatory-function","relationship":"MEASURES","relationship_label":"Measures","fidelity":"MODERATE","fidelity_label":"Moderate","description":"Measures the transcriptional and protein-stability consequences of individual patient missense variants.","limitations":"An overexpression system in a neuroblastoma line, so the dosage is not physiological and the cell type is not a striatal projection neuron. Two variants were profiled, so the shared 28-gene signature is not established across the allelic spectrum.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[],"biological_processes":[],"pathways":[],"genes":[],"chemicals":[],"readouts":[],"evidence":[{"reference":"PMID:32112337","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/32112337","reference_title":"Unraveling Molecular Mechanisms of THAP1 Missense Mutations in DYT6 Dystonia.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Transcriptional profiling using microarrays revealed a set of 28 common genes dysregulated in two mutated THAP1 (S21T and F81L) overexpression cell lines suggesting a common mechanism of these mutations.","explanation":"Reports the shared dysregulated gene set this model contributes."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Torsion_Dystonia_6","model_node_id":"model:kb/disorders/Torsion_Dystonia_6.yaml:THAP1 mutant stable neuronal cell lines","focus_node_id":"node:disorder%3ATorsion_Dystonia_6:pathophysiology:Reduced%20THAP1%20Transcriptional%20Regulatory%20Function","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Torsion_Dystonia_6.html#pathograph","nodes":[{"id":"model:kb/disorders/Torsion_Dystonia_6.yaml:THAP1 mutant stable neuronal cell lines","kind":"experimental_model","kind_label":"NAM model","label":"THAP1 mutant stable neuronal cell lines","description":"SK-N-AS neuroblastoma lines stably expressing wild-type or patient-derived mutant THAP1, used for transcriptional profiling and protein stability testing.","url":"https://dismech.monarchinitiative.org/pages/disorders/Torsion_Dystonia_6.html#experimental-model-thap1-mutant-stable-neuronal-cell-lines","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ATorsion_Dystonia_6:pathophysiology:Reduced%20THAP1%20Transcriptional%20Regulatory%20Function","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reduced THAP1 Transcriptional Regulatory Function","description":"The convergence point of the variant classes. THAP1 is a zinc-finger transcription factor, and disease variants reduce its regulatory output either by impairing sequence-specific DNA binding, by reducing protein stability and so effective dosage, or by abolishing recruitment of the HCFC1 cofactor at promoters THAP1 still binds. The last of these is the reason a variant can be pathogenic with normal DNA binding.","url":"https://dismech.monarchinitiative.org/pages/disorders/Torsion_Dystonia_6.html#pathophysiology-reduced-thap1-transcriptional-regulatory-function","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ATorsion_Dystonia_6:pathophysiology:Derepression%20of%20TOR1A","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Derepression of TOR1A","description":"THAP1 binds the core promoter of TOR1A and represses it; DYT6-associated mutant THAP1 represses it less. TOR1A is the gene mutated in DYT1 dystonia, so this is the molecular link between the two commonest monogenic isolated dystonias, and it is the reason a transcription-factor disease and a torsinA-protein disease can converge on one clinical syndrome.\nRecorded as a distinct node rather than folded into the SP1 arm because the binding is direct and demonstrated by promoter assay and ChIP, whereas the SP1 arm is an indirect expression-level effect. No downstream edge is asserted from here: how much of the dystonia is attributable to TOR1A derepression rather than to the wider expression change is not established by the curated evidence.","url":"https://dismech.monarchinitiative.org/pages/disorders/Torsion_Dystonia_6.html#pathophysiology-derepression-of-tor1a","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ATorsion_Dystonia_6:pathophysiology:Heterozygous%20THAP1%20Loss-of-Function%20Variants","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Heterozygous THAP1 Loss-of-Function Variants","description":"Heterozygous variants in THAP1, most often missense changes affecting the N-terminal THAP DNA-binding domain, but also frameshift and nonsense alleles. 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The loss is of assembled complex rather than of transcription: the subunit genes are intact and the defect is post-translational.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_31.html#pathophysiology-complex-i-assembly-failure","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_31:pathophysiology:Isolated%20Complex%20I%20Deficiency","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Isolated Complex I Deficiency","description":"The biochemical signature is an isolated complex I defect: where skeletal muscle respiratory chain enzymology was performed in reported patients it confirmed complex I deficiency with the other complexes spared, and the discovery cohort found the same isolated pattern in muscle.\nThis node carries the entry's most clinically consequential negative claim. Plasma lactate was not raised and routine metabolic investigation was unremarkable in the reported cases, so the deficiency is invisible to the screening tests that normally raise suspicion of mitochondrial disease. A normal lactate does not exclude this diagnosis.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_31.html#pathophysiology-isolated-complex-i-deficiency","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_31:pathophysiology:Loss%20of%20TIMMDC1%20Protein","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Loss of TIMMDC1 Protein","description":"TIMMDC1 is a multi-pass inner mitochondrial membrane protein that acts as an assembly factor for complex I, and in particular for the biogenesis of the mitochondrially encoded core subunit ND1. Patient cells carrying the poison-exon allele have almost no detectable TIMMDC1 protein; in the discovery cohort the protein could not be detected at all by quantitative proteomics.\nThe node is kept separate from the splicing node because it is the level at which the rescue experiments read out: restoring the protein is what the antisense oligonucleotides achieve, and what everything downstream is then measured against.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_31.html#pathophysiology-loss-of-timmdc1-protein","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_31.yaml:TIMMDC1 c.597-1340A>G patient dermal fibroblasts","source_id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_31.yaml:TIMMDC1 c.597-1340A>G patient dermal fibroblasts","target_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_31:pathophysiology:Complex%20I%20Assembly%20Failure","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"HIGH","causal_link_type":null,"causal_link_type_label":null,"description":"Patient fibroblasts reproduce the assembly defect at the protein level - reduced TIMMDC1, ND1 and other complex I subunits by quantitative proteomics.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_31:2:0","source_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_31:pathophysiology:Complex%20I%20Assembly%20Failure","target_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_31:pathophysiology:Isolated%20Complex%20I%20Deficiency","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Fewer mature holoenzymes means less NADH:ubiquinone oxidoreductase activity, with complexes II-V unaffected.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_31:1:0","source_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_31:pathophysiology:Loss%20of%20TIMMDC1%20Protein","target_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_31:pathophysiology:Complex%20I%20Assembly%20Failure","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"TIMMDC1 is required for assembly of the membrane arm and for ND1 module biogenesis; without it the holoenzyme does not mature.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0}]}},{"target":"Bioenergetic Failure in Neurons and Muscle","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_31.html#pathophysiology-bioenergetic-failure-in-neurons-and-muscle","relationship":"RECAPITULATES","relationship_label":"Recapitulates","fidelity":"MODERATE","fidelity_label":"Moderate","description":"The same cells reproduce the bioenergetic consequence, measured as respiration.","limitations":"MODERATE rather than HIGH because the node it models is about neurons and muscle and the measurement is in fibroblasts; the deficit is the same in kind but the tissue is not the affected one.","biological_scale":"CELLULAR","anatomy":[],"cell_types":[{"id":"CL:0000540","label":"neuron","display_label":"neuron","url":"http://purl.obolibrary.org/obo/CL_0000540"},{"id":"CL:0000057","label":"fibroblast","display_label":"dermal fibroblast","url":"http://purl.obolibrary.org/obo/CL_0000057"}],"biological_processes":[{"id":"GO:0042775","label":"mitochondrial ATP synthesis coupled electron transport","display_label":"mitochondrial ATP synthesis coupled electron transport","url":"http://purl.obolibrary.org/obo/GO_0042775"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"Basal oxygen consumption rate, ATP production and maximal respiration","description":null,"target":"Bioenergetic Failure in Neurons and Muscle","direction":"DECREASED","interpretation":"Seahorse extracellular flux measurement showing low basal OCR, ATP production and maximal respiration in patient fibroblasts.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:35091571","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/35091571","reference_title":"Oligonucleotide correction of an intronic TIMMDC1 variant in cells of patients with severe neurodegenerative disorder.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Patient fibroblasts showed low basal levels of OCR, ATP production and maximal respiration that were significantly increased on SSO1 or SSO2, but not NC5, treatment","explanation":"The measurement and its direction, together with the rescue arm."}],"notes":null}],"evidence":[{"reference":"PMID:35091571","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/35091571","reference_title":"Oligonucleotide correction of an intronic TIMMDC1 variant in cells of patients with severe neurodegenerative disorder.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Due to severe reduction in the abundance of TIMMDC1 protein and complex I subunits in the patient fibroblasts relative to controls, we predicted this would result in a substantial loss of mitochondrial function, particularly ATP production.","explanation":"States the reasoning connecting the assembly defect measured in these cells to the bioenergetic readout."},{"reference":"PMID:35091571","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/35091571","reference_title":"Oligonucleotide correction of an intronic TIMMDC1 variant in cells of patients with severe neurodegenerative disorder.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Patient fibroblasts showed low basal levels of OCR, ATP production and maximal respiration that were significantly increased on SSO1 or SSO2, but not NC5, treatment","explanation":"The measurement and its direction, together with the rescue arm."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Mitochondrial_Complex_I_Deficiency_Nuclear_Type_31","model_node_id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_31.yaml:TIMMDC1 c.597-1340A>G patient dermal fibroblasts","focus_node_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_31:pathophysiology:Bioenergetic%20Failure%20in%20Neurons%20and%20Muscle","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_31.html#pathograph","nodes":[{"id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_31.yaml:TIMMDC1 c.597-1340A>G patient dermal fibroblasts","kind":"experimental_model","kind_label":"NAM model","label":"TIMMDC1 c.597-1340A>G patient dermal fibroblasts","description":"Dermal fibroblasts from the two affected homozygous siblings, with heterozygous parental and unrelated healthy-control fibroblasts as comparators. 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Reported children have hypotonia and developmental delay with a predominant sensorimotor axonal neuropathy, optic atrophy and cognitive deficit; some show basal ganglia lesions on MRI, and the course is progressive and has been fatal in early childhood in the reported deep-intronic cases.\nMarked PROVISIONAL: the clinical picture is well documented but no neuropathological or tissue-level study of TIMMDC1 disease has been published, so the tissue mechanism is assumed from the complex I deficiency rather than observed.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_31.html#pathophysiology-central-and-peripheral-neurodegeneration","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_31:pathophysiology:Isolated%20Complex%20I%20Deficiency","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Isolated Complex I Deficiency","description":"The biochemical signature is an isolated complex I defect: where skeletal muscle respiratory chain enzymology was performed in reported patients it confirmed complex I deficiency with the other complexes spared, and the discovery cohort found the same isolated pattern in muscle.\nThis node carries the entry's most clinically consequential negative claim. Plasma lactate was not raised and routine metabolic investigation was unremarkable in the reported cases, so the deficiency is invisible to the screening tests that normally raise suspicion of mitochondrial disease. A normal lactate does not exclude this diagnosis.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_31.html#pathophysiology-isolated-complex-i-deficiency","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:1:model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_31.yaml:TIMMDC1 c.597-1340A>G patient dermal fibroblasts","source_id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_31.yaml:TIMMDC1 c.597-1340A>G patient dermal fibroblasts","target_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_31:pathophysiology:Bioenergetic%20Failure%20in%20Neurons%20and%20Muscle","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[1]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"The same cells reproduce the bioenergetic consequence, measured as respiration.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_31:4:0","source_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_31:pathophysiology:Bioenergetic%20Failure%20in%20Neurons%20and%20Muscle","target_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_31:pathophysiology:Central%20and%20Peripheral%20Neurodegeneration","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[4].downstream[0]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"The step from chronic ATP deficit to neuronal loss is the least characterised link in this chain and is inherited from the general mitochondrial-disease literature rather than demonstrated for TIMMDC1; typed INDIRECT_UNKNOWN_INTERMEDIATES for that reason.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_31:3:0","source_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_31:pathophysiology:Isolated%20Complex%20I%20Deficiency","target_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_31:pathophysiology:Bioenergetic%20Failure%20in%20Neurons%20and%20Muscle","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[3].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Reduced electron entry at complex I lowers ATP output in the tissues least able to tolerate it.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0}]}},{"target":"TIMMDC1 Poison-Exon Inclusion","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_31.html#pathophysiology-timmdc1-poison-exon-inclusion","relationship":"RESCUES","relationship_label":"Rescues","fidelity":"HIGH","fidelity_label":"High","description":"Treating the same fibroblasts with splice-switching oligonucleotides suppresses poison-exon inclusion and restores TIMMDC1 protein, which is the strongest available argument that the intronic variant is the cause rather than a bystander.","limitations":"The rescue is in cultured patient fibroblasts over 48 hours. 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Because the lesion is a splicing defect in a ubiquitously expressed gene, fibroblasts carry the full molecular phenotype - poison-exon transcript, absent protein, reduced complex I subunits and reduced respiration - which is why a skin biopsy substitutes for inaccessible neural tissue here.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_31.html#experimental-model-timmdc1-c-597-1340a-g-patient-dermal-fibroblasts","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_31:pathophysiology:TIMMDC1%20Poison-Exon%20Inclusion","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"TIMMDC1 Poison-Exon Inclusion","description":"The recurrent pathogenic allele is not a coding change. c.597-1340A>G (equivalently c.596+2146A>G under the earlier transcript numbering) lies deep within intron 5 and acts as a splicing enhancer, causing an ~80 bp cryptic exon to be spliced into the mature transcript between exons 5 and 6. The inserted exon shifts the reading frame and introduces a premature termination codon (p.Gly199_Thr200ins5*), so the aberrant message is degraded by nonsense-mediated decay.\nCurated as the trigger node rather than as a variant annotation because the splicing event is the mechanism: everything downstream follows from the transcript, and the one available therapeutic handle acts here and nowhere else.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_31.html#pathophysiology-timmdc1-poison-exon-inclusion","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_31:pathophysiology:Loss%20of%20TIMMDC1%20Protein","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Loss of TIMMDC1 Protein","description":"TIMMDC1 is a multi-pass inner mitochondrial membrane protein that acts as an assembly factor for complex I, and in particular for the biogenesis of the mitochondrially encoded core subunit ND1. Patient cells carrying the poison-exon allele have almost no detectable TIMMDC1 protein; in the discovery cohort the protein could not be detected at all by quantitative proteomics.\nThe node is kept separate from the splicing node because it is the level at which the rescue experiments read out: restoring the protein is what the antisense oligonucleotides achieve, and what everything downstream is then measured against.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_31.html#pathophysiology-loss-of-timmdc1-protein","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:2:model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_31.yaml:TIMMDC1 c.597-1340A>G patient dermal 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coupled electron transport","mRNA splicing, via spliceosome","nuclear-transcribed mRNA catabolic process, nonsense-mediated decay"],"pathway_terms":[],"pathways":[],"gene_terms":[{"id":"hgnc:1321","label":"TIMMDC1","display_label":"TIMMDC1","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/1321"}],"genes":["TIMMDC1"],"chemical_terms":[],"chemicals":[],"readout_names":["Complex I subunit abundance by quantitative proteomics","Basal oxygen consumption rate, ATP production and maximal respiration","TIMMDC1 protein level after splice-switching oligonucleotide treatment"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:35091571","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/35091571","reference_title":"Oligonucleotide correction of an intronic TIMMDC1 variant in cells of patients with severe neurodegenerative disorder.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Using RNA and protein analysis we show almost complete loss of TIMMDC1 protein and compromised mitochondrial complex I function.","explanation":"Supports treating patient fibroblasts as informative for the assembly node."},{"reference":"PMID:35091571","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/35091571","reference_title":"Oligonucleotide correction of an intronic TIMMDC1 variant in cells of patients with severe neurodegenerative disorder.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"a Volcano plot expressing quantitative proteomics data showing a decreased abundance of TIMMDC1 and other complex I subunits in patient III-2 relative to healthy control (n = 5) whole fibroblasts.","explanation":"The proteomic measurement behind this readout, with its control comparator."},{"reference":"PMID:35091571","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/35091571","reference_title":"Oligonucleotide correction of an intronic TIMMDC1 variant in cells of patients with severe neurodegenerative disorder.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Due to severe reduction in the abundance of TIMMDC1 protein and complex I subunits in the patient fibroblasts relative to controls, we predicted this would result in a substantial loss of mitochondrial function, particularly ATP production.","explanation":"States the reasoning connecting the assembly defect measured in these cells to the bioenergetic readout."},{"reference":"PMID:35091571","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/35091571","reference_title":"Oligonucleotide correction of an intronic TIMMDC1 variant in cells of patients with severe neurodegenerative disorder.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Patient fibroblasts showed low basal levels of OCR, ATP production and maximal respiration that were significantly increased on SSO1 or SSO2, but not NC5, treatment","explanation":"The measurement and its direction, together with the rescue arm."},{"reference":"PMID:35091571","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/35091571","reference_title":"Oligonucleotide correction of an intronic TIMMDC1 variant in cells of patients with severe neurodegenerative disorder.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Quantitative proteomics and real-time metabolic analysis of mitochondrial function on patient fibroblasts treated with SSOs showed restoration of complex I subunit abundance and function.","explanation":"Supports the model as a rescue system for the splicing node, at both the proteomic and the functional level."},{"reference":"PMID:35091571","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/35091571","reference_title":"Oligonucleotide correction of an intronic TIMMDC1 variant in cells of patients with severe neurodegenerative disorder.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"As expected, TIMMDC1 protein levels recovered in SSO1 and SSO2 treated affected fibroblasts that had negligible basal levels as observed in NC5 treated fibroblasts","explanation":"The rescue measurement with its non-targeting control."}],"evidence_text":["Using RNA and protein analysis we show almost complete loss of TIMMDC1 protein and compromised mitochondrial complex I function.","a Volcano plot expressing quantitative proteomics data showing a decreased abundance of TIMMDC1 and other complex I subunits in patient III-2 relative to healthy control (n = 5) whole fibroblasts.","Due to severe reduction in the abundance of TIMMDC1 protein and complex I subunits in the patient fibroblasts relative to controls, we predicted this would result in a substantial loss of mitochondrial function, particularly ATP production.","Patient fibroblasts showed low basal levels of OCR, ATP production and maximal respiration that were significantly increased on SSO1 or SSO2, but not NC5, treatment","Quantitative proteomics and real-time metabolic analysis of mitochondrial function on patient fibroblasts treated with SSOs showed restoration of complex I subunit abundance and function.","As expected, TIMMDC1 protein levels recovered in SSO1 and SSO2 treated affected fibroblasts that had negligible basal levels as observed in NC5 treated fibroblasts","Supports treating patient fibroblasts as informative for the assembly node.","The proteomic measurement behind this readout, with its control comparator.","States the reasoning connecting the assembly defect measured in these cells to the bioenergetic readout.","The measurement and its direction, together with the rescue arm.","Supports the model as a rescue system for the splicing node, at both the proteomic and the functional level.","The rescue measurement with its non-targeting control."],"evidence_status":"Evidence recorded","metadata_completeness":60,"metadata_present":["Model category","Organism","Cell type","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Anatomy","Cell source","Culture system"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_31.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_31.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_31.html#experimental-model-timmdc1-c-597-1340a-g-patient-dermal-fibroblasts","source_anchor":"experimental-model-timmdc1-c-597-1340a-g-patient-dermal-fibroblasts"},{"id":"model:kb/disorders/Autosomal_Recessive_Optic_Atrophy_OPA7_Type.yaml:TMEM126A-depleted HEK293 cells with protease and paralog 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OXA1L-fragment experiments used serum-free culture and translation-permissive isolated-mitochondria conditions; clone and assay context affect the findings.","notes":null,"context_id":"disorder:Autosomal_Recessive_Optic_Atrophy_OPA7_Type","context_kind":"Disorder","disease_name":"Autosomal Recessive Optic Atrophy OPA7 Type","disease_synonyms":["OPA7","TMEM126A-related optic atrophy","autosomal recessive optic atrophy, OPA7","nonsyndromic autosomal recessive optic atrophy"],"disease_term":{"id":"MONDO:0013069","label":"autosomal recessive optic atrophy, OPA7 type","display_label":"autosomal recessive optic atrophy, OPA7 type","url":"http://purl.obolibrary.org/obo/MONDO_0013069"},"experimental_model_type":"CELL_LINE","experimental_model_type_label":"Cell line","namo_type":"namo:CellLineModel","declared_namo_class_name":null,"namo_class_name":"CellLineModel","namo_class_label":"Cell Line Model","namo_description":"A model system based on immortalized cell lines that can be maintained in culture indefinitely. Examples: HepG2, A549, Caco-2, etc.","namo_docs_url":"https://monarch-initiative.github.io/namo/elements/CellLineModel/","namo_ontology_url":"https://w3id.org/monarch-initiative/namo/CellLineModel","namo_mapping_basis":"Safe mapping from DisMech category","namo_class_in_schema":true,"namo_schema_status":"Defined in NAMO schema used for this build","modality":"Cellular system","organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":"HEK293 cells subjected to siRNA depletion or CRISPR-Cas9 knockout","source_category":"Immortalized / cell line","culture_system":null,"publication":"PMID:38199007","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38199007","mechanisms":[{"target":"Reduced TMEM126B Abundance","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Recessive_Optic_Atrophy_OPA7_Type.html#pathophysiology-reduced-tmem126b-abundance","relationship":"RECAPITULATES","relationship_label":"Recapitulates","fidelity":"NOT_SPECIFIED","fidelity_label":"Not Specified","description":"TMEM126B protein abundance falls after TMEM126A loss.","limitations":"Immortalized non-retinal cells do not establish allele-specific patient effects or retinal ganglion-cell degeneration.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[],"biological_processes":[],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"TMEM126B protein abundance","description":null,"target":"Reduced TMEM126B Abundance","direction":"DECREASED","interpretation":null,"biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:38199007","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38199007","reference_title":"Identification of TMEM126A as OXA1L-interacting protein reveals cotranslational quality control in mitochondria.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"in isolated mitochondria from TMEM126A knockdown cells, we observed that the TMEM126B steady-state levels were drastically reduced compared with the non-targeting control","explanation":"TMEM126B abundance decreases after TMEM126A knockdown; rescue establishes the relevance of this secondary loss to complex I in the same system."}],"notes":null}],"evidence":[{"reference":"PMID:38199007","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38199007","reference_title":"Identification of TMEM126A as OXA1L-interacting protein reveals cotranslational quality control in mitochondria.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"in isolated mitochondria from TMEM126A knockdown cells, we observed that the TMEM126B steady-state levels were drastically reduced compared with the non-targeting control","explanation":"TMEM126B abundance decreases after TMEM126A knockdown; rescue establishes the relevance of this secondary loss to complex I in the same system."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Autosomal_Recessive_Optic_Atrophy_OPA7_Type","model_node_id":"model:kb/disorders/Autosomal_Recessive_Optic_Atrophy_OPA7_Type.yaml:TMEM126A-depleted HEK293 cells with protease and paralog rescue","focus_node_id":"node:disorder%3AAutosomal_Recessive_Optic_Atrophy_OPA7_Type:pathophysiology:Reduced%20TMEM126B%20Abundance","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Recessive_Optic_Atrophy_OPA7_Type.html#pathograph","nodes":[{"id":"model:kb/disorders/Autosomal_Recessive_Optic_Atrophy_OPA7_Type.yaml:TMEM126A-depleted HEK293 cells with protease and paralog rescue","kind":"experimental_model","kind_label":"NAM model","label":"TMEM126A-depleted HEK293 cells with protease and paralog rescue","description":"The 2024 study combined two knockout clones, acute depletion, OXA1L interaction and cleavage assays, metabolic labeling, and TMEM126B or YME1L perturbations. 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Re-expression of untagged TMEM126B restores complex I assembly and activity, supporting secondary paralog depletion as a cause of that phenotype in this model. The mechanism lowering TMEM126B and its importance in patient retinal ganglion cells remain undetermined.","url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Recessive_Optic_Atrophy_OPA7_Type.html#pathophysiology-reduced-tmem126b-abundance","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAutosomal_Recessive_Optic_Atrophy_OPA7_Type:pathophysiology:Impaired%20Complex%20I%20Assembly","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Complex I Assembly","description":"TMEM126A loss reduces assembled respiratory complex I. The 2021 HEK293T study found transient association with newly synthesized ND4 and slower ND4 labeling without faster turnover of the labeled pool, supporting an early biogenesis role. A 2024 HEK293 study instead attributed its complex I defect to secondary TMEM126B loss: untagged TMEM126B rescued assembly and activity, whereas C-terminally FLAG-tagged TMEM126B did not. 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Notably this defect does not extend to inflammation generally: the patients mount normal clinical and biological inflammatory responses, and blood leukocyte subset development is normal.","url":"https://dismech.monarchinitiative.org/pages/disorders/Immunodeficiency_127.html#pathophysiology-absent-macrophage-tnf-production","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AImmunodeficiency_127:pathophysiology:Failure%20of%20Macrophage%20Control%20of%20Listeria%20monocytogenes","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Failure of Macrophage Control of Listeria monocytogenes","description":"The same macrophage defect impairs control of a second intramacrophagic organism. GM-CSF-matured monocyte-derived macrophages from both patients yielded more Listeria monocytogenes colony-forming units than controls, and TNF stimulation reduced viable bacteria — the same rescue logic that establishes the respiratory burst edge. Infliximab-treated control macrophages reproduce the phenotype. This is why the defect is better stated as impaired control of intramacrophagic bacteria than as M. tuberculosis-specific.","url":"https://dismech.monarchinitiative.org/pages/disorders/Immunodeficiency_127.html#pathophysiology-failure-of-macrophage-control-of-listeria-monocytogenes","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AImmunodeficiency_127:pathophysiology:Failure%20of%20Macrophage%20Control%20of%20Mycobacterium%20tuberculosis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Failure of Macrophage Control of Mycobacterium tuberculosis","description":"Without a competent respiratory burst, macrophages cannot restrict Mycobacterium tuberculosis. The defect is selective rather than absent elsewhere: immunity to weakly virulent mycobacteria — including BCG — and to many other infectious agents is preserved, so these individuals are not broadly infection-prone, but control of at least one other intramacrophagic organism, Listeria monocytogenes, is also impaired.","url":"https://dismech.monarchinitiative.org/pages/disorders/Immunodeficiency_127.html#pathophysiology-failure-of-macrophage-control-of-mycobacterium-tuberculosis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Immunodeficiency_127.yaml:TNF- and TNFR1-deficient iPSC-derived GM-CSF-matured macrophages","source_id":"model:kb/disorders/Immunodeficiency_127.yaml:TNF- and TNFR1-deficient iPSC-derived GM-CSF-matured macrophages","target_id":"node:disorder%3AImmunodeficiency_127:pathophysiology:Impaired%20Macrophage%20Respiratory%20Burst","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"HIGH","causal_link_type":null,"causal_link_type_label":null,"description":"TNF- and TNFR1-deficient iPSC-derived macrophages reproduce the impaired respiratory burst seen in patient cells, and the deficiency is corrected by exogenous TNF.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AImmunodeficiency_127:1:0","source_id":"node:disorder%3AImmunodeficiency_127:pathophysiology:Absent%20Macrophage%20TNF%20Production","target_id":"node:disorder%3AImmunodeficiency_127:pathophysiology:Impaired%20Macrophage%20Respiratory%20Burst","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Loss of the autocrine TNF signal prevents GM-CSF-matured macrophages from acquiring a competent respiratory burst. That the link is causal and TNF-dependent is shown by rescue: adding TNF back to TNF-deficient iPSC-derived macrophages restores the burst.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AImmunodeficiency_127:2:1","source_id":"node:disorder%3AImmunodeficiency_127:pathophysiology:Impaired%20Macrophage%20Respiratory%20Burst","target_id":"node:disorder%3AImmunodeficiency_127:pathophysiology:Failure%20of%20Macrophage%20Control%20of%20Listeria%20monocytogenes","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[1]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"The same macrophage compartment fails to control Listeria monocytogenes, another intramacrophagic organism, and TNF add-back restores that 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entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Immunodeficiency_127.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Immunodeficiency_127.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Immunodeficiency_127.html#experimental-model-tnf-and-tnfr1-deficient-ipsc-derived-gm-csf-matured-macrophages","source_anchor":"experimental-model-tnf-and-tnfr1-deficient-ipsc-derived-gm-csf-matured-macrophages"},{"id":"model:kb/disorders/Dilated_Cardiomyopathy_2A.yaml:Tnni3-null (cardiac troponin I knockout) mouse","name":"Tnni3-null (cardiac troponin I knockout) mouse","description":"Germline deletion of the cardiac troponin I isoform by gene targeting in murine embryonic stem cells. 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Isolated ventricular myocytes provide the myofilament-level readouts (sarcomere length, resting tension, calcium sensitivity) that are not obtainable from patients.","notes":null,"context_id":"disorder:Dilated_Cardiomyopathy_2A","context_kind":"Disorder","disease_name":"Dilated Cardiomyopathy 2A","disease_synonyms":["CMD2A","DCM2A","cardiomyopathy, dilated, 2A","dilated cardiomyopathy type 2A","TNNI3-related autosomal recessive dilated cardiomyopathy"],"disease_term":{"id":"MONDO:0012746","label":"dilated cardiomyopathy 2A","display_label":"dilated cardiomyopathy 2A","url":"http://purl.obolibrary.org/obo/MONDO_0012746"},"experimental_model_type":"OTHER","experimental_model_type_label":"Other","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"house mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"},"organism_label":"Mus musculus","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[{"id":"CL:0000746","label":"cardiac muscle cell","display_label":"Cardiomyocyte","url":"http://purl.obolibrary.org/obo/CL_0000746"}],"model_cell_type_labels":["cardiac muscle cell"],"linked_cell_types":[{"id":"CL:0000746","label":"cardiac muscle cell","display_label":"Cardiomyocyte","url":"http://purl.obolibrary.org/obo/CL_0000746"}],"linked_cell_type_labels":["cardiac muscle cell"],"cell_types":[{"id":"CL:0000746","label":"cardiac muscle cell","display_label":"Cardiomyocyte","url":"http://purl.obolibrary.org/obo/CL_0000746"}],"cell_type_labels":["cardiac muscle cell"],"conditions":[],"cell_source":null,"source_category":null,"culture_system":null,"publication":"PMID:9915769","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/9915769","mechanisms":[{"target":"Perinatal Troponin I Isoform Switch and Loss of ssTnI Compensation","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy_2A.html#pathophysiology-perinatal-troponin-i-isoform-switch-and-loss-of-sstni-compensation","relationship":"NOT_SPECIFIED","relationship_label":"Not Specified","fidelity":"NOT_SPECIFIED","fidelity_label":"Not Specified","description":"The model's central result is the timing of ssTnI withdrawal in a cTnI-null background and the consequent onset of failure.","limitations":null,"biological_scale":"CELLULAR","anatomy":[],"cell_types":[{"id":"CL:0000746","label":"cardiac muscle cell","display_label":"Cardiomyocyte","url":"http://purl.obolibrary.org/obo/CL_0000746"}],"biological_processes":[{"id":"GO:0006942","label":"regulation of striated muscle contraction","display_label":"Regulation of striated muscle contraction","url":"http://purl.obolibrary.org/obo/GO_0006942"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[],"evidence":[{"reference":"PMID:9915769","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/9915769","reference_title":"Cardiac troponin I gene knockout: a mouse model of myocardial troponin I deficiency.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"15 days after birth slow skeletal troponin I expression began a steady decline, giving rise to a troponin I deficiency","explanation":"The model's measurement of the ssTnI withdrawal schedule that this pathophysiology node describes."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Dilated_Cardiomyopathy_2A","model_node_id":"model:kb/disorders/Dilated_Cardiomyopathy_2A.yaml:Tnni3-null (cardiac troponin I knockout) mouse","focus_node_id":"node:disorder%3ADilated_Cardiomyopathy_2A:pathophysiology:Perinatal%20Troponin%20I%20Isoform%20Switch%20and%20Loss%20of%20ssTnI%20Compensation","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy_2A.html#pathograph","nodes":[{"id":"model:kb/disorders/Dilated_Cardiomyopathy_2A.yaml:Tnni3-null (cardiac troponin I knockout) mouse","kind":"experimental_model","kind_label":"NAM model","label":"Tnni3-null (cardiac troponin I knockout) mouse","description":"Germline deletion of the cardiac troponin I isoform by gene targeting in murine embryonic stem cells. 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Isolated ventricular myocytes provide the myofilament-level readouts (sarcomere length, resting tension, calcium sensitivity) that are not obtainable from patients.","url":"https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy_2A.html#experimental-model-tnni3-null-cardiac-troponin-i-knockout-mouse","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ADilated_Cardiomyopathy_2A:pathophysiology:Perinatal%20Troponin%20I%20Isoform%20Switch%20and%20Loss%20of%20ssTnI%20Compensation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Perinatal Troponin I Isoform Switch and Loss of ssTnI Compensation","description":"The heart expresses two troponin I isoforms under developmental control: the slow skeletal isoform (ssTnI, TNNI1) in fetal and early postnatal myocardium, replaced by cardiac troponin I (cTnI, TNNI3) as the heart matures. 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This node explains the entity's most distinctive clinical feature — a well child who decompensates abruptly in the neonatal period or first months — and is why CMD2A is a disease of infancy rather than of adulthood like most sarcomeric cardiomyopathy.","url":"https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy_2A.html#pathophysiology-perinatal-troponin-i-isoform-switch-and-loss-of-sstni-compensation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ADilated_Cardiomyopathy_2A:pathophysiology:Biallelic%20TNNI3%20Loss%20of%20Function","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Biallelic TNNI3 Loss of Function","description":"TNNI3 encodes cardiac troponin I, the inhibitory subunit of the troponin complex and one of the three regulatory proteins (with troponin C and troponin T) that confer calcium sensitivity on the sarcomeric thin filament. CMD2A arises when both TNNI3 alleles are inactivated — most often by nonsense or frameshift variants (p.Arg69Alafs*8, p.Arg98*), but also by a synonymous variant creating a cryptic splice site with intron retention in trans with a whole-gene deletion. The lesion is a true loss of function rather than the dominant-negative or altered-function mechanism that characterizes the heterozygous TNNI3 missense variants responsible for hypertrophic and restrictive cardiomyopathy, which is why the disease is recessive and heterozygous carriers are largely spared.","url":"https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy_2A.html#pathophysiology-biallelic-tnni3-loss-of-function","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ADilated_Cardiomyopathy_2A:pathophysiology:Thin-Filament%20Regulatory%20Failure%20and%20Impaired%20Myofilament%20Mechanics","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Thin-Filament Regulatory Failure and Impaired Myofilament Mechanics","description":"Without any troponin I, the thin filament loses the inhibitory element that normally keeps tropomyosin over the myosin-binding sites at low calcium and that transduces calcium binding at troponin C into cooperative filament activation. 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In the recessive human allelic series the severity of this regulatory failure appears to track residual cTnI abundance.","url":"https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy_2A.html#pathophysiology-thin-filament-regulatory-failure-and-impaired-myofilament-mechanics","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Dilated_Cardiomyopathy_2A.yaml:Tnni3-null (cardiac troponin I knockout) mouse","source_id":"model:kb/disorders/Dilated_Cardiomyopathy_2A.yaml:Tnni3-null (cardiac troponin I knockout) 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In the recessive human allelic series the severity of this regulatory failure appears to track residual cTnI abundance.","url":"https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy_2A.html#pathophysiology-thin-filament-regulatory-failure-and-impaired-myofilament-mechanics","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ADilated_Cardiomyopathy_2A:pathophysiology:Left%20Ventricular%20Dilation%20and%20Systolic%20Failure","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Left Ventricular Dilation and Systolic Failure","description":"The failing myofilament produces the defining organ-level phenotype: progressive left ventricular chamber enlargement with severely depressed ejection fraction, functional mitral regurgitation from annular dilation, and congestive heart failure. Reported infants have presented with left ventricular ejection fractions as low as 10%, and the resulting circulatory failure is what kills — one reported kindred lost three siblings in the first year of life. Because the primary lesion is a permanent absence of a structural regulatory protein rather than a modifiable stress, this node does not remit; neurohormonal therapy slows it but transplantation is the only definitive intervention.","url":"https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy_2A.html#pathophysiology-left-ventricular-dilation-and-systolic-failure","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ADilated_Cardiomyopathy_2A:pathophysiology:Perinatal%20Troponin%20I%20Isoform%20Switch%20and%20Loss%20of%20ssTnI%20Compensation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Perinatal Troponin I Isoform Switch and Loss of ssTnI Compensation","description":"The heart expresses two troponin I isoforms under developmental control: the slow skeletal isoform (ssTnI, TNNI1) in fetal and early postnatal myocardium, replaced by cardiac troponin I (cTnI, TNNI3) as the heart matures. In a cTnI-null heart, ssTnI initially occupies the troponin complex and supports normal development, normal birth weight, and normal cardiac structure at birth. Critically, ssTnI downregulation proceeds on its own developmental schedule and is not held back by the absence of cTnI, so the myocardium passes from ssTnI-supported regulation to no troponin I at all. This node explains the entity's most distinctive clinical feature — a well child who decompensates abruptly in the neonatal period or first months — and is why CMD2A is a disease of infancy rather than of adulthood like most sarcomeric cardiomyopathy.","url":"https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy_2A.html#pathophysiology-perinatal-troponin-i-isoform-switch-and-loss-of-sstni-compensation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:1:model:kb/disorders/Dilated_Cardiomyopathy_2A.yaml:Tnni3-null (cardiac troponin I knockout) mouse","source_id":"model:kb/disorders/Dilated_Cardiomyopathy_2A.yaml:Tnni3-null (cardiac troponin I knockout) 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isoform of troponin I by using gene targeting in murine embryonic stem cells to determine the developmental and physiological effects of the absence of this regulatory protein.","explanation":"Describes the construction of the model and its purpose, matching the genotype of CMD2A (complete absence of cardiac troponin I)."},{"reference":"PMID:9915769","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/9915769","reference_title":"Cardiac troponin I gene knockout: a mouse model of myocardial troponin I deficiency.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"15 days after birth slow skeletal troponin I expression began a steady decline, giving rise to a troponin I deficiency","explanation":"The model's measurement of the ssTnI withdrawal schedule that this pathophysiology node describes."},{"reference":"PMID:9915769","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/9915769","reference_title":"Cardiac troponin I gene knockout: a mouse model of myocardial troponin I deficiency.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"Ventricular myocytes isolated from these troponin I-depleted hearts displayed shortened sarcomeres and elevated resting tension measured under relaxing conditions","explanation":"The myofilament-mechanics readouts the model contributes to this node."}],"evidence_text":["We deleted the cardiac isoform of troponin I by using gene targeting in murine embryonic stem cells to determine the developmental and physiological effects of the absence of this regulatory protein.","15 days after birth slow skeletal troponin I expression began a steady decline, giving rise to a troponin I deficiency","Ventricular myocytes isolated from these troponin I-depleted hearts displayed shortened sarcomeres and elevated resting tension measured under relaxing conditions","Describes the construction of the model and its purpose, matching the genotype of CMD2A (complete absence of cardiac troponin I).","The model's measurement of the ssTnI withdrawal schedule that this pathophysiology node describes.","The myofilament-mechanics readouts the model contributes to this node."],"evidence_status":"Evidence recorded","metadata_completeness":60,"metadata_present":["Model category","Organism","Cell type","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Anatomy","Cell source","Culture system"],"dataset_context":"None recorded in same 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This demonstrates an intrinsic component in the mouse system alongside the separate tongue-mechanics hypothesis.","notes":null,"context_id":"disorder:Bilateral_Microtia-Deafness-Cleft_Palate_Syndrome","context_kind":"Disorder","disease_name":"Bilateral Microtia-Deafness-Cleft Palate Syndrome","disease_synonyms":["microtia, hearing impairment, and cleft palate","microtia with or without hearing impairment","HOXA2-related microtia","MHIC"],"disease_term":{"id":"MONDO:0012854","label":"bilateral microtia-deafness-cleft palate syndrome","display_label":"bilateral microtia-deafness-cleft palate syndrome","url":"http://purl.obolibrary.org/obo/MONDO_0012854"},"experimental_model_type":"OTHER","experimental_model_type_label":"Other","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[{"id":"UBERON:0005619","label":"secondary palatal shelf","display_label":"secondary palatal shelf","url":"http://purl.obolibrary.org/obo/UBERON_0005619"}],"linked_anatomy_labels":["secondary palatal shelf"],"anatomy":[{"id":"UBERON:0005619","label":"secondary palatal shelf","display_label":"secondary palatal shelf","url":"http://purl.obolibrary.org/obo/UBERON_0005619"}],"anatomy_labels":["secondary palatal shelf"],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":null,"source_category":null,"culture_system":null,"publication":null,"publication_url":null,"mechanisms":[{"target":"Intrinsic Palatal Shelf Fusion Defect","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Bilateral_Microtia-Deafness-Cleft_Palate_Syndrome.html#pathophysiology-intrinsic-palatal-shelf-fusion-defect","relationship":"PARTIALLY_RECAPITULATES","relationship_label":"Partially Recapitulates","fidelity":"NOT_SPECIFIED","fidelity_label":"Not Specified","description":null,"limitations":"Explant fusion rates do not quantify in-vivo penetrance or establish the relative mechanism of the human partial cleft.","biological_scale":"TISSUE","anatomy":[{"id":"UBERON:0005619","label":"secondary palatal shelf","display_label":"secondary palatal shelf","url":"http://purl.obolibrary.org/obo/UBERON_0005619"}],"cell_types":[],"biological_processes":[{"id":"GO:0062009","label":"secondary palate development","display_label":"secondary palate development","url":"http://purl.obolibrary.org/obo/GO_0062009"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[],"evidence":[{"reference":"PMID:19653318","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/19653318","reference_title":"Hoxa2 plays a direct role in murine palate development.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Organ cultures of Hoxa2(-/-) palates maintained in the absence of the tongue showed decreased fusion rates than either Hoxa2(+/-) or Hoxa2(+/+) palate cultures.","explanation":"Tongue-free mouse organ culture isolates a palate-intrinsic contribution."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Bilateral_Microtia-Deafness-Cleft_Palate_Syndrome","model_node_id":"model:kb/disorders/Bilateral_Microtia-Deafness-Cleft_Palate_Syndrome.yaml:Tongue-free Hoxa2 mutant palate organ culture","focus_node_id":"node:disorder%3ABilateral_Microtia-Deafness-Cleft_Palate_Syndrome:pathophysiology:Intrinsic%20Palatal%20Shelf%20Fusion%20Defect","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Bilateral_Microtia-Deafness-Cleft_Palate_Syndrome.html#pathograph","nodes":[{"id":"model:kb/disorders/Bilateral_Microtia-Deafness-Cleft_Palate_Syndrome.yaml:Tongue-free Hoxa2 mutant palate organ culture","kind":"experimental_model","kind_label":"NAM model","label":"Tongue-free Hoxa2 mutant palate organ culture","description":"Null palatal shelves cultured without a tongue have reduced fusion; antisense Hoxa2 knockdown also reduces fusion. This demonstrates an intrinsic component in the mouse system alongside the separate tongue-mechanics hypothesis.","url":"https://dismech.monarchinitiative.org/pages/disorders/Bilateral_Microtia-Deafness-Cleft_Palate_Syndrome.html#experimental-model-tongue-free-hoxa2-mutant-palate-organ-culture","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ABilateral_Microtia-Deafness-Cleft_Palate_Syndrome:pathophysiology:Intrinsic%20Palatal%20Shelf%20Fusion%20Defect","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Intrinsic Palatal Shelf Fusion Defect","description":"A second, independent route to the same cleft. Hoxa2 is expressed in the developing palate itself between E12.5 and E15.5, and Hoxa2-null palatal shelves cultured in the absence of the tongue fuse at lower rates than heterozygous or wild-type shelves, as do shelves in which Hoxa2 is knocked down with antisense constructs. Null palates show an overall increase in cell proliferation, and Hoxa2 represses Msx1, Bmp4, Barx1 and Ptx1 within the palate. On the authors' reading the mouse cleft is therefore not solely secondary to the tongue. Whether either route operates in HOXA2-mutant humans is unknown.","url":"https://dismech.monarchinitiative.org/pages/disorders/Bilateral_Microtia-Deafness-Cleft_Palate_Syndrome.html#pathophysiology-intrinsic-palatal-shelf-fusion-defect","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ABilateral_Microtia-Deafness-Cleft_Palate_Syndrome:phenotype:Cleft%20Palate","kind":"phenotype","kind_label":"Phenotype","label":"Cleft Palate","description":"Partial cleft palate is documented in the original homozygous p.Gln186Lys family. Examined members of the p.Gln235* and p.Glu224* dominant pedigrees had an intact palate or unremarkable intraoral examination. Mouse null clefting supports developmental relevance but does not establish the specific mechanism of the human cleft.","url":"https://dismech.monarchinitiative.org/pages/disorders/Bilateral_Microtia-Deafness-Cleft_Palate_Syndrome.html#phenotype-cleft-palate","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ABilateral_Microtia-Deafness-Cleft_Palate_Syndrome:pathophysiology:HOXA2%20Loss%20of%20Function","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"HOXA2 Loss of Function","description":"Disease-associated alleles include heterozygous truncating variants p.Lys213*, p.Glu224* and p.Gln235*, and the recessive homeodomain missense p.Gln186Lys. Dominant haploinsufficiency is inferred from segregation and variant class, with impaired enhancer activation measured for two truncating alleles. The p.Gln186Lys DNA-binding effect is a homology-model prediction; the founding study did not measure residual protein activity or show functional complementation.","url":"https://dismech.monarchinitiative.org/pages/disorders/Bilateral_Microtia-Deafness-Cleft_Palate_Syndrome.html#pathophysiology-hoxa2-loss-of-function","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Bilateral_Microtia-Deafness-Cleft_Palate_Syndrome.yaml:Tongue-free Hoxa2 mutant palate organ culture","source_id":"model:kb/disorders/Bilateral_Microtia-Deafness-Cleft_Palate_Syndrome.yaml:Tongue-free Hoxa2 mutant palate organ culture","target_id":"node:disorder%3ABilateral_Microtia-Deafness-Cleft_Palate_Syndrome:pathophysiology:Intrinsic%20Palatal%20Shelf%20Fusion%20Defect","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Partially Recapitulates","directed":false,"relationship":"PARTIALLY_RECAPITULATES","fidelity":"NOT_SPECIFIED","causal_link_type":null,"causal_link_type_label":null,"description":null,"intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ABilateral_Microtia-Deafness-Cleft_Palate_Syndrome:0:2","source_id":"node:disorder%3ABilateral_Microtia-Deafness-Cleft_Palate_Syndrome:pathophysiology:HOXA2%20Loss%20of%20Function","target_id":"node:disorder%3ABilateral_Microtia-Deafness-Cleft_Palate_Syndrome:pathophysiology:Intrinsic%20Palatal%20Shelf%20Fusion%20Defect","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[2]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"A route that does not run through the pharyngeal arches at all. 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The founding study named this gain of stabilization, and it is the rate-limiting step of the disorder: everything upstream converges on it, and everything downstream follows from it.","url":"https://dismech.monarchinitiative.org/pages/disorders/Developmental_and_Epileptic_Encephalopathy_116.html#pathophysiology-escape-from-glutamine-induced-degradation-of-glutamine-synthetase","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ADevelopmental_And_Epileptic_Encephalopathy_116:pathophysiology:GLUL%20Start-Loss%20and%205%27%20UTR%20Splice%20Variants","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"GLUL Start-Loss and 5' UTR Splice Variants","description":"The disease alleles cluster on one target: the initiation codon of GLUL. They reach it two ways. 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Both are single observations and are curated here as spectrum expansion rather than as an established second mechanism.","url":"https://dismech.monarchinitiative.org/pages/disorders/Developmental_and_Epileptic_Encephalopathy_116.html#pathophysiology-glul-start-loss-and-5-utr-splice-variants","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"}],"edges":[{"id":"model-link:0:model:kb/disorders/Developmental_And_Epileptic_Encephalopathy_116.yaml:Transfection-based expression system for GLUL start-loss variants","source_id":"model:kb/disorders/Developmental_And_Epileptic_Encephalopathy_116.yaml:Transfection-based expression system for GLUL start-loss 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high.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1}]}}],"mechanism_names":["Translation Reinitiation at Methionine 18"],"relationships":["Measures"],"fidelities":["Moderate"],"biological_scales":["Molecular"],"system_context_sources":["Linked mechanism biological scale"],"modeled_system_labels":["Molecular"],"biological_process_terms":[{"id":"GO:0006413","label":"translational initiation","display_label":"translational initiation","url":"http://purl.obolibrary.org/obo/GO_0006413"}],"biological_processes":["translational initiation"],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":["Translation initiation site of the expressed protein"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:38579670","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38579670","reference_title":"Clustered de novo start-loss variants in GLUL result in a developmental and epileptic encephalopathy via stabilization of glutamine synthetase.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"resulting in a protein that is stable and enzymatically competent but insensitive to negative feedback by glutamine","explanation":"The three properties of the variant protein that this system established, all of which are claims about the molecule rather than about a tissue."},{"reference":"PMID:38579670","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38579670","reference_title":"Clustered de novo start-loss variants in GLUL result in a developmental and epileptic encephalopathy via stabilization of glutamine synthetase.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Using transfection-based expression systems and mass spectrometry, these variants were shown to lead to translation initiation of GS from methionine 18, downstream of the N-terminal degron motif","explanation":"Reports the measurement and its result."}],"evidence_text":["resulting in a protein that is stable and enzymatically competent but insensitive to negative feedback by glutamine","Using transfection-based expression systems and mass spectrometry, these variants were shown to lead to translation initiation of GS from methionine 18, downstream of the N-terminal degron motif","The three properties of the variant protein that this system established, all of which are claims about the molecule rather than about a tissue.","Reports the measurement and its result."],"evidence_status":"Evidence recorded","metadata_completeness":70,"metadata_present":["Model 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CoQ10/vitamin E prevention of stress-induced death is an in-vitro result, not clinical treatment efficacy. Full source remained unavailable beyond the complete abstract.","context_id":"disorder:Adult-Onset_Ataxia_and_Polyneuropathy","context_kind":"Disorder","disease_name":"Adult-Onset Ataxia and Polyneuropathy","disease_synonyms":["Ataxia and polyneuropathy, adult-onset","Adult-onset MT-ATP6 ataxia and axonal neuropathy"],"disease_term":{"id":"MONDO:0010781","label":"ataxia and polyneuropathy, adult-onset","display_label":"adult-onset ataxia and polyneuropathy","url":"http://purl.obolibrary.org/obo/MONDO_0010781"},"experimental_model_type":"CELL_LINE","experimental_model_type_label":"Cell line","namo_type":"namo:CellLineModel","declared_namo_class_name":null,"namo_class_name":"CellLineModel","namo_class_label":"Cell Line Model","namo_description":"A model system based on immortalized cell lines that can be maintained in culture indefinitely. Examples: HepG2, A549, Caco-2, etc.","namo_docs_url":"https://monarch-initiative.github.io/namo/elements/CellLineModel/","namo_ontology_url":"https://w3id.org/monarch-initiative/namo/CellLineModel","namo_mapping_basis":"Safe mapping from DisMech category","namo_class_in_schema":true,"namo_schema_status":"Defined in NAMO schema used for this build","modality":"Cellular system","organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":"Transmitochondrial cybrids separated a causal m.9035T>C ATP6 variant from a co-occurring tRNA-Met polymorphism; ATP, ROS and survival under glucose deprivation or oxidant stress were assessed.","source_category":"Immortalized / cell line","culture_system":null,"publication":"PMID:19626676","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/19626676","mechanisms":[{"target":"Impaired ATP Synthase Function","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Adult-Onset_Ataxia_and_Polyneuropathy.html#pathophysiology-impaired-atp-synthase-function","relationship":"PARTIALLY_RECAPITULATES","relationship_label":"Partially Recapitulates","fidelity":"LOW","fidelity_label":"Low","description":"Assay-specific evidence for mitochondrial dysfunction.","limitations":"Different ATP6 variant and immortalized cellular background. 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Full source remained unavailable beyond the complete abstract.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0015986","label":"proton motive force-driven ATP synthesis","display_label":"proton motive force-driven ATP synthesis","url":"http://purl.obolibrary.org/obo/GO_0015986"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[],"evidence":[{"reference":"PMID:19626676","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/19626676","reference_title":"Identification of ataxia-associated mtDNA mutations (m.4052T>C and m.9035T>C) and evaluation of their pathogenicity in transmitochondrial cybrids.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"They had less than half of the steady-state content of ATP and nearly an 8-fold higher basal level of reactive oxygen species (ROS).","explanation":"Quantifies the combined ATP shortfall and ROS burden in cybrids carrying an MT-ATP6 ataxia variant. Graded INDIRECT because the cybrids carried m.9035T>C."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Adult-Onset_Ataxia_and_Polyneuropathy","model_node_id":"model:kb/disorders/Adult-Onset_Ataxia_and_Polyneuropathy.yaml:Transmitochondrial m.9035T>C cybrids","focus_node_id":"node:disorder%3AAdult-Onset_Ataxia_and_Polyneuropathy:pathophysiology:Impaired%20ATP%20Synthase%20Function","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Adult-Onset_Ataxia_and_Polyneuropathy.html#pathograph","nodes":[{"id":"model:kb/disorders/Adult-Onset_Ataxia_and_Polyneuropathy.yaml:Transmitochondrial m.9035T>C cybrids","kind":"experimental_model","kind_label":"NAM model","label":"Transmitochondrial m.9035T>C cybrids","description":"Transmitochondrial cybrids separated a causal m.9035T>C ATP6 variant from a co-occurring tRNA-Met polymorphism; ATP, ROS and survival under glucose deprivation or oxidant stress were assessed.","url":"https://dismech.monarchinitiative.org/pages/disorders/Adult-Onset_Ataxia_and_Polyneuropathy.html#experimental-model-transmitochondrial-m-9035t-c-cybrids","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAdult-Onset_Ataxia_and_Polyneuropathy:pathophysiology:Impaired%20ATP%20Synthase%20Function","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired ATP Synthase Function","description":"The m.8993T>C ATP6 substitution perturbs ATP-synthase-related bioenergetics. In related m.9035T>C cybrids, F0-ATPase dysfunction was measured. Complex V subcomplexes in m.9035T>C patient material suggest altered assembly or stability, but that interpretation is provisional: oligomycin-sensitive ATP hydrolysis was normal in the later primary-fibroblast and muscle study. The assays and cellular backgrounds differ.","url":"https://dismech.monarchinitiative.org/pages/disorders/Adult-Onset_Ataxia_and_Polyneuropathy.html#pathophysiology-impaired-atp-synthase-function","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAdult-Onset_Ataxia_and_Polyneuropathy:pathophysiology:Cellular%20ATP%20Depletion","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Cellular ATP Depletion","description":"Energy deprivation was measured in m.8993T>C patient lymphocytes. Related m.9035T>C cybrids had less than half the control steady-state ATP content. 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GeneReviews describes relatively little tissue- or age-dependent heteroplasmy variation for m.8993T>C/G, unlike some other mtDNA variants. Differences among tissues can nevertheless occur, and high load does not reliably predict an individual phenotype. Nuclear, haplogroup and copy-number modifiers remain candidate explanations rather than demonstrated determinants here.","url":"https://dismech.monarchinitiative.org/pages/disorders/Adult-Onset_Ataxia_and_Polyneuropathy.html#pathophysiology-heteroplasmy-dependent-expression","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAdult-Onset_Ataxia_and_Polyneuropathy:pathophysiology:MT-ATP6%20m.8993T%3EC%20Variant","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"MT-ATP6 m.8993T>C Variant","description":"The defining mitochondrial m.8993T>C missense variant substitutes proline for leucine at ATP6 residue 156. ATP6 encodes subunit a of ATP synthase. Related adult-ataxia variants m.9035T>C and m.9185T>C have distinct assay and clinical evidence; their results are qualified wherever used.","url":"https://dismech.monarchinitiative.org/pages/disorders/Adult-Onset_Ataxia_and_Polyneuropathy.html#pathophysiology-mt-atp6-m-8993t-c-variant","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAdult-Onset_Ataxia_and_Polyneuropathy:pathophysiology:Reactive%20Oxygen%20Species%20Overproduction","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Reactive Oxygen Species Overproduction","description":"Patient lymphocytes carrying m.8993T>C showed increased ROS production, with a different balance between ROS and energy deprivation than m.8993T>G. 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Human transcriptomic studies also associate the fusion with Hippo, TGF-beta, and Hedgehog pathway dysregulation, but those associations are not modeled here as individually proven causal edges.","url":"https://dismech.monarchinitiative.org/pages/disorders/Acute_Megakaryoblastic_Leukemia.html#pathophysiology-cbfa2t3-glis2-induces-bmp-signaling-and-progenitor-self-renewal","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAcute_Megakaryoblastic_Leukemia:pathophysiology:Extramedullary%20Leukemic%20Infiltration","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Extramedullary Leukemic Infiltration","description":"Leukemic megakaryoblasts may form cohesive infiltrates in liver, lymph node, and other tissues. This is particularly well documented in infant t(1;22) AMKL and can resemble a nonhematopoietic small-round-cell tumor.","url":"https://dismech.monarchinitiative.org/pages/disorders/Acute_Megakaryoblastic_Leukemia.html#pathophysiology-extramedullary-leukemic-infiltration","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAcute_Megakaryoblastic_Leukemia:pathophysiology:HOX%20Rearrangement%20and%20MPL%2FJAK-STAT%20Cooperation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"HOX Rearrangement and MPL/JAK-STAT Cooperation","description":"HOX-rearranged pediatric AMKL is enriched for activating MPL mutations. Experimental co-expression of a HOX rearrangement and mutant MPL produces a cytokine-independent growth advantage with phosphorylated JAK2 and STAT5, supporting subgroup-specific signaling cooperation.","url":"https://dismech.monarchinitiative.org/pages/disorders/Acute_Megakaryoblastic_Leukemia.html#pathophysiology-hox-rearrangement-and-mpl-jak-stat-cooperation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAcute_Megakaryoblastic_Leukemia:pathophysiology:KMT2A-%20and%20NUP98-Rearranged%20HOXA%20Program","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"KMT2A- and NUP98-Rearranged HOXA Program","description":"KMT2A (historically MLL) and NUP98 fusions define distinct pediatric subgroups but converge at the level of HOXA-cluster upregulation. This node models the shared transcriptional program without treating KMT2A as a cooperating lesion of another fusion subgroup.","url":"https://dismech.monarchinitiative.org/pages/disorders/Acute_Megakaryoblastic_Leukemia.html#pathophysiology-kmt2a-and-nup98-rearranged-hoxa-program","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAcute_Megakaryoblastic_Leukemia:pathophysiology:Non-DS%20GATA1%20Mutation%20Cooperates%20with%20Chromosome%2021%20Gain","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Non-DS GATA1 Mutation Cooperates with Chromosome 21 Gain","description":"A non-DS pediatric subgroup carries somatic GATA1 truncation without constitutional trisomy 21. Most reported cases had acquired amplification of the Down syndrome critical region and a transcriptional profile closely resembling DS-AMKL.","url":"https://dismech.monarchinitiative.org/pages/disorders/Acute_Megakaryoblastic_Leukemia.html#pathophysiology-non-ds-gata1-mutation-cooperates-with-chromosome-21-gain","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAcute_Megakaryoblastic_Leukemia:pathophysiology:NUP98%3A%3AKDM5A%20Sustains%20Progenitor%20Capacity%20and%20Maturation%20Arrest","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"NUP98::KDM5A Sustains Progenitor Capacity and Maturation Arrest","description":"NUP98::KDM5A is a potent driver of maturation arrest and long-term proliferative/progenitor capacity in engineered human hematopoietic cells. Model systems also show JAK-STAT upregulation and drug sensitivity, but these preclinical dependencies are not established clinical treatments.","url":"https://dismech.monarchinitiative.org/pages/disorders/Acute_Megakaryoblastic_Leukemia.html#pathophysiology-nup98-kdm5a-sustains-progenitor-capacity-and-maturation-arrest","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAcute_Megakaryoblastic_Leukemia:pathophysiology:PDGF-Associated%20Marrow%20Fibrosis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"PDGF-Associated Marrow Fibrosis","description":"AMKL marrow commonly shows reticulin fibrosis. In a clinicopathologic series, PDGF-BB staining in megakaryoblasts and some fibroblasts tracked with the presence of fibrosis, supporting a growth-factor-associated stromal response while leaving additional mediators unresolved.","url":"https://dismech.monarchinitiative.org/pages/disorders/Acute_Megakaryoblastic_Leukemia.html#pathophysiology-pdgf-associated-marrow-fibrosis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAcute_Megakaryoblastic_Leukemia:pathophysiology:RBM15%3A%3AMRTFA%20Fusion%20Deregulates%20RBPJ%20Transcription","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"RBM15::MRTFA Fusion Deregulates RBPJ Transcription","description":"The t(1;22) fusion joins RBM15 to MRTFA (formerly MKL1). In a knock-in mouse model the fusion deregulates RBPJ-mediated canonical Notch transcription and abnormal fetal megakaryopoiesis; cooperation with activating MPL is required for short-latency model disease.","url":"https://dismech.monarchinitiative.org/pages/disorders/Acute_Megakaryoblastic_Leukemia.html#pathophysiology-rbm15-mrtfa-fusion-deregulates-rbpj-transcription","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAcute_Megakaryoblastic_Leukemia:phenotype:Thrombocytopenia","kind":"phenotype","kind_label":"Phenotype","label":"Thrombocytopenia","description":"Platelet counts are often low, although normal counts can occur. Frequency is intentionally omitted because available cohorts do not support one universal AMKL-wide category.","url":"https://dismech.monarchinitiative.org/pages/disorders/Acute_Megakaryoblastic_Leukemia.html#phenotype-thrombocytopenia","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:2:model:kb/disorders/Acute_Megakaryoblastic_Leukemia.yaml:Trisomy-21 GATA1/STAG2 Double-Mutant iPSC Model","source_id":"model:kb/disorders/Acute_Megakaryoblastic_Leukemia.yaml:Trisomy-21 GATA1/STAG2 Double-Mutant iPSC Model","target_id":"node:disorder%3AAcute_Megakaryoblastic_Leukemia:pathophysiology:Immature%20Megakaryocytic%20Leukemic%20State","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[2]","label":"Not 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CRISPR/Cas9 to introduce a co-operating mutation in STAG2, a member of the cohesin complex recurrently mutated in DS-ML but not in TAM.","explanation":"This directly identifies the engineered cooperating lesion in the iPSC system."},{"reference":"PMID:35203280","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/35203280","reference_title":"Modeling Down Syndrome Myeloid Leukemia by Sequential Introduction of GATA1 and STAG2 Mutations in Induced Pluripotent Stem Cells with Trisomy 21.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Hematopoietic differentiation of GATA1&nbsp;STAG2 double-mutant iPSC lines confirmed GATA1s expression and the loss of functional STAG2 protein, leading to enhanced production of immature megakaryocytic population compared to GATA1 mutant alone.","explanation":"This directly supports the immature-megakaryocytic-state readout."},{"reference":"PMID:35203280","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/35203280","reference_title":"Modeling 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differentiation of GATA1&nbsp;STAG2 double-mutant iPSC lines confirmed GATA1s expression and the loss of functional STAG2 protein, leading to enhanced production of immature megakaryocytic population compared to GATA1 mutant alone.","Megakaryocyte-specific lineage expansion of the double-mutant HSPCs exhibited close resemblance to the DS-ML immunophenotype.","The publication explicitly identifies the engineered iPSC system as a DS-ML model.","This directly supports the model link to trisomy-21-associated GATA1s production.","This directly identifies the engineered cooperating lesion in the iPSC system.","This directly supports the immature-megakaryocytic-state readout.","This is the source's direct phenotypic characterization of the double-mutant lineage-expansion experiment."],"evidence_status":"Evidence recorded","metadata_completeness":90,"metadata_present":["Model category","Organism","Anatomy","Cell type","Cell source","Culture system","Modeled 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The reporting authors read that as evidence that complex I expression is itself regulated by ROS, which makes this node a feedback modifier on the assembly node rather than a terminal consequence.\nIt is curated PROVISIONAL because the causal claim rests on the correlated response to one intervention in cultured fibroblasts, and because the authors describe the contribution of ROS to pathogenesis as supported by circumstantial evidence.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_2.html#pathophysiology-increased-reactive-oxygen-species-production","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_2:pathophysiology:Complex%20I%20Assembly%20and%20Stability%20Failure","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Complex I Assembly and Stability Failure","description":"Western blotting of patient material shows not only a deficiency of the NDUFS8 polypeptide itself - which a mutation in its own gene would produce trivially - but reductions in other nuclear-encoded subunits of complex I as well. That second observation is the informative one: the rest of the complex cannot be maintained without TYKY, so the subunit is required for assembly, for stability of the assembled enzyme, or for both. The available data do not distinguish those alternatives, and the reporting authors do not claim to.\nThere is a structural proposal for what the subunit is doing. NDUFS8/TYKY is thought to connect the membrane and peripheral domains of complex I - the boundary between the arm embedded in the inner membrane and the arm that carries the electron relay. A subunit at that junction is exactly the kind whose loss would destabilise the whole assembly rather than remove one catalytic step. Consistent with that, the late-onset patient also showed a drastic reduction in the 39-kDa subunit, which is proposed to sit at the same domain boundary and may interact with TYKY directly.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_2.html#pathophysiology-complex-i-assembly-and-stability-failure","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_2:pathophysiology:Impaired%20NADH-Ubiquinone%20Oxidoreduction%20and%20OXPHOS%20Deficit","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired NADH-Ubiquinone Oxidoreduction and OXPHOS Deficit","description":"Reduced NADH oxidation and electron delivery to ubiquinone lower proton pumping and oxidative phosphorylation capacity. Two consequences follow that are visible in patient cells: the mitochondrial membrane potential falls, and NADH that cannot be reoxidized through the respiratory chain accumulates - which is why exogenous NAD+ and pyruvate, both of which restore cytosolic NAD+ regeneration, rescue these cells.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_2.html#pathophysiology-impaired-nadh-ubiquinone-oxidoreduction-and-oxphos-deficit","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"}],"edges":[{"id":"model-link:0:model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_2.yaml:Trolox-treated complex I-deficient patient fibroblasts (NDUFS1/S2/S7/S8/V1)","source_id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_2.yaml:Trolox-treated complex I-deficient patient fibroblasts (NDUFS1/S2/S7/S8/V1)","target_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_2:pathophysiology:Increased%20Reactive%20Oxygen%20Species%20Production","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Perturbs","directed":false,"relationship":"PERTURBS","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"Chronic antioxidant treatment lowers ROS and raises the amount of complex I, which is the experimental basis for treating ROS as a feedback regulator of complex I expression rather than as a downstream by-product.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_2:3:1","source_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_2:pathophysiology:Impaired%20NADH-Ubiquinone%20Oxidoreduction%20and%20OXPHOS%20Deficit","target_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_2:pathophysiology:Increased%20Reactive%20Oxygen%20Species%20Production","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[3].downstream[1]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"A partially blocked, over-reduced electron transport chain leaks electrons to oxygen.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_2:5:0","source_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_2:pathophysiology:Increased%20Reactive%20Oxygen%20Species%20Production","target_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_2:pathophysiology:Complex%20I%20Assembly%20and%20Stability%20Failure","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[5].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Proposed negative feedback: lowering ROS raises the amount of assembled complex I, so raised ROS is inferred to suppress it. Curated as an inference from one interventional experiment, not as an established loop.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0}]}}],"mechanism_names":["Increased Reactive Oxygen Species Production"],"relationships":["Perturbs"],"fidelities":["Moderate"],"biological_scales":["Cellular"],"system_context_sources":["Model-level cell type","Linked mechanism cell type","Linked mechanism biological scale"],"modeled_system_labels":["fibroblast","Cellular"],"biological_process_terms":[{"id":"GO:0072593","label":"reactive oxygen species metabolic process","display_label":"reactive oxygen species metabolic process","url":"http://purl.obolibrary.org/obo/GO_0072593"}],"biological_processes":["reactive oxygen species metabolic process"],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":["Cellular ROS level under chronic Trolox","Ratio of complex I activity increase to amount increase"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:18435906","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/18435906","reference_title":"Mitigation of NADH: ubiquinone oxidoreductase deficiency by chronic Trolox treatment.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Our findings suggest that the expression of complex I is regulated by ROS.","explanation":"The authors' inference from this perturbation, which is what the ROS node rests on."},{"reference":"PMID:18435906","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/18435906","reference_title":"Mitigation of NADH: ubiquinone oxidoreductase deficiency by chronic Trolox treatment.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Trolox treatment dramatically reduced ROS levels in both control and patient cells, which was paralleled by a substantial increase in the amount of complex I.","explanation":"The ROS measurement and the paired complex I response."},{"reference":"PMID:18435906","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/18435906","reference_title":"Mitigation of NADH: ubiquinone oxidoreductase deficiency by chronic Trolox treatment.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Although the ratio between the increase in activity and amount of complex I was exactly proportional in control cells it varied between 0.1 and 0.8 for the patients.","explanation":"The quantitative disproportion between recovered enzyme and recovered function."}],"evidence_text":["Our findings suggest that the expression of complex I is regulated by ROS.","Trolox treatment dramatically reduced ROS levels in both control and patient cells, which was paralleled by a substantial increase in the amount of complex I.","Although the ratio between the increase in activity and amount of complex I was exactly proportional in control cells it varied between 0.1 and 0.8 for the patients.","The authors' inference from this perturbation, which is what the ROS node rests on.","The ROS measurement and the paired complex I response.","The quantitative disproportion between recovered enzyme and recovered function."],"evidence_status":"Evidence recorded","metadata_completeness":60,"metadata_present":["Model category","Organism","Cell type","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Anatomy","Cell source","Culture system"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_2.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_2.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency,_Nuclear_Type_2.html#experimental-model-trolox-treated-complex-i-deficient-patient-fibroblasts-ndufs1-s2-s7-s8-v1","source_anchor":"experimental-model-trolox-treated-complex-i-deficient-patient-fibroblasts-ndufs1-s2-s7-s8-v1"},{"id":"model:kb/disorders/AA_Amyloidosis.yaml:Truncated human SAA peptide assembly","name":"Truncated human SAA peptide assembly","description":"Cell-free human SAA(1–76) was compared with full-length SAA in a heparan-sulfate-induced assembly system. CD, FTIR and electron microscopy assess conformation and fibrils.","notes":null,"context_id":"disorder:AA_Amyloidosis","context_kind":"Disorder","disease_name":"AA Amyloidosis","disease_synonyms":["secondary amyloidosis","reactive systemic amyloidosis","inflammatory amyloidosis","amyloid A amyloidosis","serum amyloid A amyloidosis"],"disease_term":{"id":"MONDO:0019439","label":"AA amyloidosis","display_label":"AA amyloidosis","url":"http://purl.obolibrary.org/obo/MONDO_0019439"},"experimental_model_type":"OTHER","experimental_model_type_label":"Other","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":null,"source_category":null,"culture_system":null,"publication":"PMID:29288051","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/29288051","mechanisms":[{"target":"Reduced Alpha-Helical Structure of Truncated SAA","target_url":"https://dismech.monarchinitiative.org/pages/disorders/AA_Amyloidosis.html#pathophysiology-reduced-alpha-helical-structure-of-truncated-saa","relationship":"RECAPITULATES","relationship_label":"Recapitulates","fidelity":"LOW","fidelity_label":"Low","description":"Tests the direct structural consequence of a defined C-terminal truncation.","limitations":"Only the abstract is available after attempted regeneration. 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This experimentally observed conformational effect is distinct from the unresolved timing of proteolysis in tissue deposits.","url":"https://dismech.monarchinitiative.org/pages/disorders/AA_Amyloidosis.html#pathophysiology-reduced-alpha-helical-structure-of-truncated-saa","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAA_Amyloidosis:pathophysiology:SAA%20Amyloid%20Fibril%20Assembly","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"SAA Amyloid Fibril Assembly","description":"SAA species assemble into cross-beta amyloid fibrils through nucleation and elongation. Truncation and extracellular cofactors can alter kinetics, while preformed fibrils provide seeds. 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the experiment tests a defined fragment rather than proving when proteolysis occurs in vivo.","Truncation accelerates fibril assembly in this experimental system; full-length protein can form fibrils under other conditions."],"evidence_status":"Evidence recorded","metadata_completeness":40,"metadata_present":["Model category","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Organism","Anatomy","Cell type","Cell source","Culture system"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/AA_Amyloidosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/AA_Amyloidosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/AA_Amyloidosis.html#experimental-model-truncated-human-saa-peptide-assembly","source_anchor":"experimental-model-truncated-human-saa-peptide-assembly"},{"id":"model:kb/disorders/Axial_Spondylometaphyseal_Dysplasia.yaml:Trypanosome CFAP410 N-terminal domain and localization","name":"Trypanosome CFAP410 N-terminal domain and localization","description":"Purified trypanosome N-terminal domains test solubility of human disease-equivalent substitutions; 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In NEK1-knockout cells, both wild-type and kinase-dead NEK1 restored CFAP410 abundance, whereas association-defective variants did not; kinase activity and complex-dependent abundance are therefore separable requirements.","url":"https://dismech.monarchinitiative.org/pages/disorders/Axial_Spondylometaphyseal_Dysplasia.html#pathophysiology-disruption-of-the-cfap410-nek1-complex","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAxial_Spondylometaphyseal_Dysplasia:pathophysiology:Biallelic%20CFAP410%20or%20NEK1%20Loss%20of%20Function","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Biallelic CFAP410 or NEK1 Loss of Function","description":"Biallelic CFAP410 variants include missense and splice-altering alleles. 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TSC2 protein was also expressed in giant cells in fetal cortical tubers (Fig. S7D), consistent with previous data (26, 27). This suggests that second-hit events are not a prerequisite for tuber formation.","explanation":"Wild-type TSC2 in nearly all giant cells means the model produces tuber cells without the second hit, which is a failure to recapitulate the node rather than a low-fidelity version of it."},{"reference":"PMID:35084981","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/35084981","reference_title":"Amplification of human interneuron progenitors promotes brain tumors and neurological defects.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"TSC2 protein expression was detected in over 98% of giant cells using an antibody recognizing only the wild type TSC2 variant","explanation":"Reports the giant-cell TSC2 immunostaining measurement."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Tuberous_Sclerosis_Complex","model_node_id":"model:kb/disorders/Tuberous_Sclerosis_Complex.yaml:TSC human cerebral organoids with caudal late interneuron progenitor (CLIP) over-proliferation","focus_node_id":"node:disorder%3ATuberous_Sclerosis_Complex:pathophysiology:Somatic%20Second%20Hit%20at%20TSC%20Locus","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Tuberous_Sclerosis_Complex.html#pathograph","nodes":[{"id":"model:kb/disorders/Tuberous_Sclerosis_Complex.yaml:TSC human cerebral organoids with caudal late interneuron progenitor (CLIP) over-proliferation","kind":"experimental_model","kind_label":"NAM model","label":"TSC human cerebral organoids with caudal late interneuron progenitor (CLIP) over-proliferation","description":"Cerebral organoids identify a human-specific interneuron progenitor population that over-proliferates in TSC, generating excess interneurons, tumours and cortical malformations; EGFR inhibition reduces tumour burden.","url":"https://dismech.monarchinitiative.org/pages/disorders/Tuberous_Sclerosis_Complex.html#experimental-model-tsc-human-cerebral-organoids-with-caudal-late-interneuron-progenitor-clip-over-proliferation","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ATuberous_Sclerosis_Complex:pathophysiology:Somatic%20Second%20Hit%20at%20TSC%20Locus","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Somatic Second Hit at TSC Locus","description":"Loss of the wild-type TSC1 or TSC2 allele (loss of heterozygosity, LOH) or an acquired pathogenic variant in lesion precursor cells results in biallelic inactivation of the TSC complex and full release of RHEB-GTPase inhibition. The two-hit model accounts for the focal nature of hamartomas (cortical tubers, angiomyolipomas, SEGAs, rhabdomyomas, LAM) despite a germline heterozygous mutation. Approximately 10-15% of clinically definite TSC cases have no germline pathogenic variant identified, with low-level somatic mosaicism postulated as the underlying mechanism. The requirement for a second hit is well established for the classic hamartomas but is not universal across lesion classes: mesenchymal tumorigenesis in the TSC2+/- mouse proceeds from haploinsufficiency alone and is HMGA2- rather than mTOR-dependent, with mTOR pathway activation detectable in only half of the corresponding human tumours.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Tuberous_Sclerosis_Complex.html#pathophysiology-somatic-second-hit-at-tsc-locus","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ATuberous_Sclerosis_Complex:pathophysiology:Constitutive%20mTORC1%20Hyperactivation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Constitutive mTORC1 Hyperactivation","description":"Loss of TSC1/TSC2 GAP activity allows persistent RHEB-GTP loading at the lysosomal membrane, leading to constitutive activation of mTORC1 kinase activity. Active mTORC1 phosphorylates downstream effectors (S6K1, 4E-BP1, ULK1, lipin-1, TFEB) that drive translation, anabolic biosynthesis, cell growth, and suppression of autophagy. mTORC1 signalling is constitutively active within all TSC-associated lesions and is the central, druggable pathobiological hub of the disease.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Tuberous_Sclerosis_Complex.html#pathophysiology-constitutive-mtorc1-hyperactivation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ATuberous_Sclerosis_Complex:pathophysiology:TSC1%2FTSC2%20Loss%20of%20Function%20%28Germline%20First%20Hit%29","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"TSC1/TSC2 Loss of Function (Germline First Hit)","description":"Heterozygous loss-of-function variants in TSC1 (hamartin) or TSC2 (tuberin) disrupt the TSC1/TSC2 protein complex, which normally functions as a GTPase-activating protein (GAP) for the small GTPase RHEB. The germline pathogenic variant constitutes the \"first hit\" in a Knudson two-hit model; by itself it produces haploinsufficiency but typical hamartomatous lesions require a somatic second hit at the TSC locus.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Tuberous_Sclerosis_Complex.html#pathophysiology-tsc1-tsc2-loss-of-function-germline-first-hit","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Tuberous_Sclerosis_Complex.yaml:TSC human cerebral organoids with caudal late interneuron progenitor (CLIP) over-proliferation","source_id":"model:kb/disorders/Tuberous_Sclerosis_Complex.yaml:TSC human cerebral organoids with caudal late interneuron progenitor (CLIP) over-proliferation","target_id":"node:disorder%3ATuberous_Sclerosis_Complex:pathophysiology:Somatic%20Second%20Hit%20at%20TSC%20Locus","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Fails To Recapitulate","directed":false,"relationship":"FAILS_TO_RECAPITULATE","fidelity":"NOT_SPECIFIED","causal_link_type":null,"causal_link_type_label":null,"description":"Giant cells in TSC2+/- patient organoids retain wild-type TSC2 protein, so tuber-like cells form here without the somatic second hit this node requires; the authors conclude bi-allelic inactivation is dispensable for disease initiation in human tissue.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3ATuberous_Sclerosis_Complex:2:0","source_id":"node:disorder%3ATuberous_Sclerosis_Complex:pathophysiology:Somatic%20Second%20Hit%20at%20TSC%20Locus","target_id":"node:disorder%3ATuberous_Sclerosis_Complex:pathophysiology:Constitutive%20mTORC1%20Hyperactivation","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Biallelic loss of TSC1/TSC2 in lesion cells removes GAP activity for RHEB and produces constitutive mTORC1 activation in the affected clone.\n","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3ATuberous_Sclerosis_Complex:0:0","source_id":"node:disorder%3ATuberous_Sclerosis_Complex:pathophysiology:TSC1%2FTSC2%20Loss%20of%20Function%20%28Germline%20First%20Hit%29","target_id":"node:disorder%3ATuberous_Sclerosis_Complex:pathophysiology:Somatic%20Second%20Hit%20at%20TSC%20Locus","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"A second somatic hit at the wild-type TSC1 or TSC2 allele in lesion precursor cells is required for full TSC1/TSC2 complex inactivation and focal hamartomatous lesion growth. This explains the focal, mosaic-like distribution of cortical tubers, angiomyolipomas, SEGAs, and rhabdomyomas despite a constitutional germline mutation.\n","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0}]}},{"target":"Subependymal Glioneuronal Tumor Growth","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Tuberous_Sclerosis_Complex.html#pathophysiology-subependymal-glioneuronal-tumor-growth","relationship":"RECAPITULATES","relationship_label":"Recapitulates","fidelity":"MODERATE","fidelity_label":"Moderate","description":"CLIP cell over-proliferation in TSC organoids produces brain tumours, matching the subependymal tumour growth node and proposing its human-specific cell of origin.","limitations":"Organoid tumours lack the ventricular location, vasculature and growth timescale of a subependymal giant cell astrocytoma.","biological_scale":null,"anatomy":[{"id":"UBERON:0000955","label":"brain","display_label":"brain","url":"http://purl.obolibrary.org/obo/UBERON_0000955"}],"cell_types":[{"id":"CL:0000127","label":"astrocyte","display_label":"astrocyte","url":"http://purl.obolibrary.org/obo/CL_0000127"}],"biological_processes":[{"id":"GO:0008283","label":"cell population proliferation","display_label":"cell population proliferation","url":"http://purl.obolibrary.org/obo/GO_0008283"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[{"name":"CLIP cell proliferation","description":null,"target":"Subependymal Glioneuronal Tumor Growth","direction":"INCREASED","interpretation":"The interneuron progenitor population over-proliferates in TSC organoids.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:35084981","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/35084981","reference_title":"Amplification of human interneuron progenitors promotes brain tumors and neurological defects.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"In TSC, CLIP cells over-proliferate, generating excessive interneurons, brain tumors, and cortical malformations.","explanation":"Reports the proliferation measurement."}],"notes":null},{"name":"Tumour burden under EGFR inhibition","description":null,"target":"Subependymal Glioneuronal Tumor Growth","direction":"DECREASED","interpretation":"EGFR inhibition reduces organoid tumour burden.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:35084981","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/35084981","reference_title":"Amplification of human interneuron progenitors promotes brain tumors and neurological defects.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Epidermal growth factor receptor inhibition reduces tumor burden","explanation":"Reports the treatment-arm measurement."}],"notes":null}],"evidence":[{"reference":"PMID:35084981","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/35084981","reference_title":"Amplification of human interneuron progenitors promotes brain tumors and neurological defects.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"In TSC, CLIP cells over-proliferate, generating excessive interneurons, brain tumors, and cortical malformations. Epidermal growth factor receptor inhibition reduces tumor burden, identifying potential treatment options for TSC and related disorders.","explanation":"Tumour formation from an over-proliferating progenitor in a human model supports the tumour-growth node."},{"reference":"PMID:35084981","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/35084981","reference_title":"Amplification of human interneuron progenitors promotes brain tumors and neurological defects.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"In TSC, CLIP cells over-proliferate, generating excessive interneurons, brain tumors, and cortical malformations.","explanation":"Reports the proliferation measurement."},{"reference":"PMID:35084981","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/35084981","reference_title":"Amplification of human interneuron progenitors promotes brain tumors and neurological defects.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Epidermal growth factor receptor inhibition reduces tumor burden","explanation":"Reports the treatment-arm measurement."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Tuberous_Sclerosis_Complex","model_node_id":"model:kb/disorders/Tuberous_Sclerosis_Complex.yaml:TSC human cerebral organoids with caudal late interneuron progenitor (CLIP) over-proliferation","focus_node_id":"node:disorder%3ATuberous_Sclerosis_Complex:pathophysiology:Subependymal%20Glioneuronal%20Tumor%20Growth","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Tuberous_Sclerosis_Complex.html#pathograph","nodes":[{"id":"model:kb/disorders/Tuberous_Sclerosis_Complex.yaml:TSC human cerebral organoids with caudal late interneuron progenitor (CLIP) over-proliferation","kind":"experimental_model","kind_label":"NAM model","label":"TSC human cerebral organoids with caudal late interneuron progenitor (CLIP) over-proliferation","description":"Cerebral organoids identify a human-specific interneuron progenitor population that over-proliferates in TSC, generating excess interneurons, tumours and cortical malformations; EGFR inhibition reduces tumour burden.","url":"https://dismech.monarchinitiative.org/pages/disorders/Tuberous_Sclerosis_Complex.html#experimental-model-tsc-human-cerebral-organoids-with-caudal-late-interneuron-progenitor-clip-over-proliferation","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ATuberous_Sclerosis_Complex:pathophysiology:Subependymal%20Glioneuronal%20Tumor%20Growth","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Subependymal Glioneuronal Tumor Growth","description":"mTOR-driven growth along the ventricular subependymal region produces subependymal nodules; a subset enlarge into subependymal giant cell astrocytomas that may obstruct cerebrospinal fluid flow.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Tuberous_Sclerosis_Complex.html#pathophysiology-subependymal-glioneuronal-tumor-growth","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ATuberous_Sclerosis_Complex:pathophysiology:mTOR-Driven%20Multisystem%20Hamartoma%20Growth","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"mTOR-Driven Multisystem Hamartoma Growth","description":"Constitutive mTORC1 activity increases anabolic growth programs and cell population expansion. 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defects.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"TSC2 protein expression was detected in over 98% of giant cells using an antibody recognizing only the wild type TSC2 variant (patient 1, 98.4%; patient 2, 98.7%: Fig. S7A-C). TSC2 protein was also expressed in giant cells in fetal cortical tubers (Fig. S7D), consistent with previous data (26, 27). This suggests that second-hit events are not a prerequisite for tuber formation.","explanation":"Wild-type TSC2 in nearly all giant cells means the model produces tuber cells without the second hit, which is a failure to recapitulate the node rather than a low-fidelity version of it."},{"reference":"PMID:35084981","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/35084981","reference_title":"Amplification of human interneuron progenitors promotes brain tumors and neurological defects.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"TSC2 protein expression was detected in over 98% of giant cells using an antibody recognizing only the wild type TSC2 variant","explanation":"Reports the giant-cell TSC2 immunostaining measurement."},{"reference":"PMID:35084981","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/35084981","reference_title":"Amplification of human interneuron progenitors promotes brain tumors and neurological defects.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"In TSC, CLIP cells over-proliferate, generating excessive interneurons, brain tumors, and cortical malformations. Epidermal growth factor receptor inhibition reduces tumor burden, identifying potential treatment options for TSC and related disorders.","explanation":"Tumour formation from an over-proliferating progenitor in a human model supports the tumour-growth node."},{"reference":"PMID:35084981","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/35084981","reference_title":"Amplification of human interneuron progenitors promotes brain tumors and neurological defects.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"In TSC, CLIP cells over-proliferate, generating excessive interneurons, brain tumors, and cortical malformations.","explanation":"Reports the proliferation measurement."},{"reference":"PMID:35084981","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/35084981","reference_title":"Amplification of human interneuron progenitors promotes brain tumors and neurological defects.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Epidermal growth factor receptor inhibition reduces tumor burden","explanation":"Reports the treatment-arm measurement."},{"reference":"PMID:35084981","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/35084981","reference_title":"Amplification of human interneuron progenitors promotes brain tumors and neurological defects.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"generating excessive interneurons, brain tumors, and cortical malformations","explanation":"Reports the structural measurement."}],"evidence_text":["We generated a human cerebral organoid model for tuberous sclerosis complex (TSC) and identified a specific neural stem cell type, caudal late interneuron progenitor (CLIP) cells.","TSC2 protein expression was detected in over 98% of giant cells using an antibody recognizing only the wild type TSC2 variant (patient 1, 98.4%; patient 2, 98.7%: Fig. S7A-C). TSC2 protein was also expressed in giant cells in fetal cortical tubers (Fig. S7D), consistent with previous data (26, 27). This suggests that second-hit events are not a prerequisite for tuber formation.","TSC2 protein expression was detected in over 98% of giant cells using an antibody recognizing only the wild type TSC2 variant","In TSC, CLIP cells over-proliferate, generating excessive interneurons, brain tumors, and cortical malformations. Epidermal growth factor receptor inhibition reduces tumor burden, identifying potential treatment options for TSC and related disorders.","In TSC, CLIP cells over-proliferate, generating excessive interneurons, brain tumors, and cortical malformations.","Epidermal growth factor receptor inhibition reduces tumor burden","generating excessive interneurons, brain tumors, and cortical malformations","Establishes the organoid model and the cell population it identifies.","Wild-type TSC2 in nearly all giant cells means the model produces tuber cells without the second hit, which is a failure to recapitulate the node rather than a low-fidelity version of it.","Reports the giant-cell TSC2 immunostaining measurement.","Tumour formation from an over-proliferating progenitor in a human model supports the tumour-growth node.","Reports the proliferation measurement.","Reports the treatment-arm measurement.","Reports the structural measurement."],"evidence_status":"Evidence recorded","metadata_completeness":90,"metadata_present":["Model category","NAMO class","Organism","Anatomy","Cell type","Cell source","Modeled mechanism","Publication","Evidence"],"metadata_missing":["Culture system"],"dataset_context":"Available in same entry","context_dataset_ids":["dataset:dbgap:phs001357","dataset:ega:egas00001002485","dataset:ega:egas00001004586","dataset:ega:egas00001007264","dataset:massive:msv000088551"],"candidate_dataset_ids":[],"source_path":"kb/disorders/Tuberous_Sclerosis_Complex.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Tuberous_Sclerosis_Complex.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Tuberous_Sclerosis_Complex.html#experimental-model-tsc-human-cerebral-organoids-with-caudal-late-interneuron-progenitor-clip-over-proliferation","source_anchor":"experimental-model-tsc-human-cerebral-organoids-with-caudal-late-interneuron-progenitor-clip-over-proliferation"},{"id":"model:kb/disorders/Tuberous_Sclerosis_Complex.yaml:TSC patient-derived neurovascular unit (iPSC blood-brain-barrier chip)","name":"TSC patient-derived neurovascular unit (iPSC blood-brain-barrier chip)","description":"A human microphysiological blood-brain-barrier model assembled from TSC-patient iPSC-derived endothelium and astrocytes. 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An equivalent TSC1-mutant neurovascular-unit model was not identified in this curation pass; the mechanism is expected to be shared because both proteins act through the same TSC complex, but that expectation is untested here.","context_id":"disorder:Tuberous_Sclerosis_Complex","context_kind":"Disorder","disease_name":"Tuberous Sclerosis Complex","disease_synonyms":[],"disease_term":{"id":"MONDO:0001734","label":"tuberous sclerosis","display_label":"Tuberous Sclerosis Complex","url":"http://purl.obolibrary.org/obo/MONDO_0001734"},"experimental_model_type":"ORGAN_ON_CHIP","experimental_model_type_label":"Organ-on-chip","namo_type":"namo:OrganOnChip","declared_namo_class_name":null,"namo_class_name":"OrganOnChip","namo_class_label":"Organ On Chip","namo_description":"A model system that simulates the physiological functions of an organ using a microfluidic device. Examples: Airway-on-chip, ... 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This node captures the glial and neurovascular contribution to epileptogenesis and to the cognitive/behavioural comorbidities of TAND, which the dysplasia node above does not.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Tuberous_Sclerosis_Complex.html#pathophysiology-mtor-driven-gliopathy-and-neurovascular-unit-dysfunction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3ATuberous_Sclerosis_Complex:phenotype:Cerebral%20Hypomyelination","kind":"phenotype","kind_label":"Phenotype","label":"Cerebral Hypomyelination","description":"Hypomyelination and abnormal white-matter microstructure are part of the TSC brain phenotype and are increasingly attributed to oligodendrocyte-lineage mTORC1 dysregulation rather than being a purely secondary consequence of tuber burden or seizures. 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iPSC-derived cells in a microfluidic culture platform.\n"},{"reference":"PMID:38783199","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38783199","reference_title":"Rescue of impaired blood-brain barrier in tuberous sclerosis complex patient derived neurovascular unit.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Using microphysiological systems, we demonstrate that a BBB generated from TSC2 heterozygous mutant cells shows increased permeability. 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This can be rescued by wild type astrocytes or by treatment with rapamycin, an mTOR kinase inhibitor.","Describes the construction of the model system - iPSC-derived cells in a microfluidic culture platform.","Directly demonstrates the modelled mechanism and its astrocyte-dependence and mTOR-dependence."],"evidence_status":"Evidence recorded","metadata_completeness":90,"metadata_present":["Model category","NAMO class","Organism","Anatomy","Cell type","Cell source","Culture system","Modeled mechanism","Evidence"],"metadata_missing":["Publication"],"dataset_context":"Available in same entry","context_dataset_ids":["dataset:dbgap:phs001357","dataset:ega:egas00001002485","dataset:ega:egas00001004586","dataset:ega:egas00001007264","dataset:massive:msv000088551"],"candidate_dataset_ids":[],"source_path":"kb/disorders/Tuberous_Sclerosis_Complex.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Tuberous_Sclerosis_Complex.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Tuberous_Sclerosis_Complex.html#experimental-model-tsc-patient-derived-neurovascular-unit-ipsc-blood-brain-barrier-chip","source_anchor":"experimental-model-tsc-patient-derived-neurovascular-unit-ipsc-blood-brain-barrier-chip"},{"id":"model:kb/disorders/Autosomal_Recessive_Nonsyndromic_Hearing_Loss_98.yaml:TSPEAR siRNA in keratinocytes and hair-follicle organ cultures","name":"TSPEAR siRNA in keratinocytes and hair-follicle organ cultures","description":"Comparative ectodermal-development experiments used primary human keratinocytes, a DLL1-stimulated HaCaT Notch reporter, and ex vivo skin strips from K14-H2B-GFP mice. 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No hearing test was part of this model."}],"evidence_text":["Luciferase activity in TSPEAR down-regulated cells was significantly decreased as compared with control cells, supporting a role for TSPEAR in the regulation of Notch signaling (Fig 3E).","Moreover, TSPEAR silencing in mouse hair follicle organ cultures was found to induce apoptosis in follicular epithelial cells, resulting in decreased hair bulb diameter.","The measured Notch response comes from the transfected HaCaT system; it is not an inner-ear readout.","This ex vivo mouse-tissue experiment supports an ectodermal function. No hearing test was part of this model."],"evidence_status":"Evidence recorded","metadata_completeness":30,"metadata_present":["Model category","Publication","Evidence"],"metadata_missing":["NAMO class","Organism","Anatomy","Cell type","Cell source","Culture system","Modeled mechanism"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Autosomal_Recessive_Nonsyndromic_Hearing_Loss_98.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autosomal_Recessive_Nonsyndromic_Hearing_Loss_98.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Recessive_Nonsyndromic_Hearing_Loss_98.html#experimental-model-tspear-sirna-in-keratinocytes-and-hair-follicle-organ-cultures","source_anchor":"experimental-model-tspear-sirna-in-keratinocytes-and-hair-follicle-organ-cultures"},{"id":"model:kb/disorders/Bannayan-Riley-Ruvalcaba_Syndrome.yaml:TTN p.Cys5096Arg edited HEK293T cells","name":"TTN p.Cys5096Arg edited HEK293T cells","description":"Wild-type, heterozygous, and homozygous TTN p.Cys5096Arg cells were compared for growth after confluence, viability, migration, and signaling. 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Cellular assays extend this to p.Gly73Trp and p.Arg56Leu, which reduce action-potential-triggered vesicle fusion and are associated with the more severe, epilepsy-bearing phenotype.","url":"https://dismech.monarchinitiative.org/pages/disorders/VAMP2-Related_Neurodevelopmental_Disorder.html#pathophysiology-dominant-negative-interference-with-wild-type-vamp2","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AVAMP2-Related_Disorder:pathophysiology:Impaired%20SNARE-Mediated%20Vesicle%20Fusion","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired SNARE-Mediated Vesicle Fusion","description":"VAMP2 is one of the three core neuronal SNAREs whose zippering, triggered by the calcium sensor synaptotagmin-1, fuses the synaptic vesicle with the presynaptic membrane. The fusion defect is variant-specific rather than uniform across the allelic series: in the reconstituted lipid-mixing assay p.Ser75Pro reduced fusion to roughly 25% of wild-type and could not be activated by Munc18-1 (a >90% loss-of-function under Munc18-activated conditions), whereas p.Glu78Ala was indistinguishable from wild-type and p.Phe77Ser could not be purified for testing. In cultured neurons, two of three variants tested reduced both the rate of exocytosis and the size of the released recycling pool. The authors therefore frame impaired fusion as one of the possible mechanisms and explicitly invoke mutation-specific mechanisms; for variants without a reconstituted fusion defect, disrupted interaction with regulatory proteins absent from the assay is the proposed alternative. This is the module's key conformance target — the fusion-machinery arm.","url":"https://dismech.monarchinitiative.org/pages/disorders/VAMP2-Related_Neurodevelopmental_Disorder.html#pathophysiology-impaired-snare-mediated-vesicle-fusion","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AVAMP2-Related_Disorder:pathophysiology:VAMP2%20v-SNARE%20Defect","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"VAMP2 v-SNARE Defect","description":"De novo variants affect conserved residues of the VAMP2 SNARE motif (residues 31-91) — the region whose zippering with syntaxin-1 and SNAP-25 provides the energy for membrane fusion. Three allelic classes are reported — a scheme that is the literature's and not exhaustive, since a de novo start-loss variant (c.1A>G, p.Met1?) fits none of them: non-synonymous variants within the motif, of which the three index-cohort variants (p.Ser75Pro, p.Phe77Ser, p.Glu78Ala) cluster in its C-terminal portion, with p.Gly73Trp reported adjacent to that cluster and p.Arg56Leu, p.Arg66Pro and p.Ala67Pro lying further N-terminally; in-frame single-amino-acid deletions at more N-terminal residues (p.Val43del, p.Ile45del); and truncating loss-of-function variants (p.Arg56*, p.Tyr113Glnfs*12). VAMP2 is the vesicle-associated (v-)SNARE essential for vesicular exocytosis and activity-dependent neurotransmitter release, so these variants act directly on the fusion machinery. The downstream route differs by allelic class: SNARE-motif missense variants act dominant-negatively, whereas truncating variants are proposed to act through haploinsufficiency.","url":"https://dismech.monarchinitiative.org/pages/disorders/VAMP2-Related_Neurodevelopmental_Disorder.html#pathophysiology-vamp2-v-snare-defect","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/VAMP2-Related_Disorder.yaml:Variant-expressing cultured neurons with synaptophysin-pHluorin imaging","source_id":"model:kb/disorders/VAMP2-Related_Disorder.yaml:Variant-expressing cultured neurons with synaptophysin-pHluorin imaging","target_id":"node:disorder%3AVAMP2-Related_Disorder:pathophysiology:Dominant-Negative%20Interference%20with%20Wild-Type%20VAMP2","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Measures","directed":false,"relationship":"MEASURES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"Distinguishes SNARE-motif missense variants, which suppress action-potential-triggered fusion in the presence of endogenous wild-type VAMP2, from the nonsense variant, which does not.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AVAMP2-Related_Disorder:1:0","source_id":"node:disorder%3AVAMP2-Related_Disorder:pathophysiology:Dominant-Negative%20Interference%20with%20Wild-Type%20VAMP2","target_id":"node:disorder%3AVAMP2-Related_Disorder:pathophysiology:Impaired%20SNARE-Mediated%20Vesicle%20Fusion","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":null,"intermediate_mechanisms":[],"hypothesis_groups":["dominant_negative_snare_interference"],"evidence_count":1},{"id":"causal:disorder%3AVAMP2-Related_Disorder:0:0","source_id":"node:disorder%3AVAMP2-Related_Disorder:pathophysiology:VAMP2%20v-SNARE%20Defect","target_id":"node:disorder%3AVAMP2-Related_Disorder:pathophysiology:Dominant-Negative%20Interference%20with%20Wild-Type%20VAMP2","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Route taken by SNARE-motif missense variants, which produce a stable protein that is incorporated into SNARE complexes.","intermediate_mechanisms":[],"hypothesis_groups":["dominant_negative_snare_interference"],"evidence_count":1}]}}],"mechanism_names":["Dominant-Negative Interference with Wild-Type VAMP2"],"relationships":["Measures"],"fidelities":["Moderate"],"biological_scales":["Molecular"],"system_context_sources":["Linked mechanism cell type","Linked mechanism biological scale"],"modeled_system_labels":["neuron","Molecular"],"biological_process_terms":[],"biological_processes":[],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":["Rate of exocytosis and size of the released recycling pool"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:32906212","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/32906212","reference_title":"Overcoming presynaptic effects of VAMP2 mutations with 4-aminopyridine treatment.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"we used live cell imaging of an optical reporter of SV recycling, synaptophysin-pHluorin (syp-pH).","explanation":"Establishes the reporter and imaging approach that define this model system."},{"reference":"PMID:32906212","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/32906212","reference_title":"Overcoming presynaptic effects of VAMP2 mutations with 4-aminopyridine treatment.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Synaptic vesicle recycling and neurotransmission were assayed in neurons expressing three VAMP2 variants by live-cell imaging and electrophysiology.","explanation":"Establishes the model system and the assays applied."},{"reference":"PMID:32906212","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/32906212","reference_title":"Overcoming presynaptic effects of VAMP2 mutations with 4-aminopyridine treatment.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"In cellular models, two variants decrease both the rate of exocytosis and the number of synaptic vesicles released from the recycling pool, compared with wild-type.","explanation":"The primary readout distinguishing variants with and without a cellular release defect."}],"evidence_text":["we used live cell imaging of an optical reporter of SV recycling, synaptophysin-pHluorin (syp-pH).","Synaptic vesicle recycling and neurotransmission were assayed in neurons expressing three VAMP2 variants by live-cell imaging and electrophysiology.","In cellular models, two variants decrease both the rate of exocytosis and the number of synaptic vesicles released from the recycling pool, compared with wild-type.","Establishes the reporter and imaging approach that define this model system.","Establishes the model system and the assays applied.","The primary readout distinguishing variants with and without a cellular release defect."],"evidence_status":"Evidence recorded","metadata_completeness":50,"metadata_present":["Model category","Cell type","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Organism","Anatomy","Cell source","Culture system"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/VAMP2-Related_Disorder.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/VAMP2-Related_Disorder.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/VAMP2-Related_Neurodevelopmental_Disorder.html#experimental-model-variant-expressing-cultured-neurons-with-synaptophysin-phluorin-imaging","source_anchor":"experimental-model-variant-expressing-cultured-neurons-with-synaptophysin-phluorin-imaging"},{"id":"model:kb/disorders/Anauxetic_Dysplasia.yaml:Variant-specific RNase MRP substrate-cleavage assay","name":"Variant-specific RNase MRP substrate-cleavage assay","description":"Variant-specific cleavage assays separate the rRNA activity that tracks skeletal severity from the mRNA activity that tracks CHH-like hair, immune, and haematologic manifestations. The assays support substrate-specific genotype-phenotype correlation but do not model growth-plate architecture.","notes":null,"context_id":"disorder:Anauxetic_Dysplasia","context_kind":"Disorder","disease_name":"Anauxetic dysplasia","disease_synonyms":["AD","spondyloepimetaphyseal dysplasia, anauxetic type"],"disease_term":{"id":"MONDO:0011773","label":"anauxetic dysplasia","display_label":"anauxetic dysplasia","url":"http://purl.obolibrary.org/obo/MONDO_0011773"},"experimental_model_type":"OTHER","experimental_model_type_label":"Other","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},"organism_label":"Homo sapiens","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":["Thirteen disease-associated RMRP variants","Wild-type RNase MRP activity comparator"],"cell_source":"Reconstituted human RNase MRP complexes carrying patient RMRP variants","source_category":"Patient-derived","culture_system":"In vitro messenger-RNA and ribosomal-RNA cleavage assays","publication":"PMID:17701897","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/17701897","mechanisms":[{"target":"Impaired rRNA Cleavage in Ribosome Assembly","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Anauxetic_dysplasia.html#pathophysiology-impaired-rrna-cleavage-in-ribosome-assembly","relationship":"NOT_SPECIFIED","relationship_label":"Not Specified","fidelity":"NOT_SPECIFIED","fidelity_label":"Not Specified","description":"Quantifies variant-specific loss of rRNA cleavage against bone-dysplasia severity.","limitations":null,"biological_scale":"MOLECULAR","anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0006364","label":"rRNA processing","display_label":"rRNA processing","url":"http://purl.obolibrary.org/obo/GO_0006364"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[],"evidence":[{"reference":"PMID:17701897","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/17701897","reference_title":"Type and level of RMRP functional impairment predicts phenotype in the cartilage hair hypoplasia-anauxetic dysplasia spectrum.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"In vitro testing of RNase MRP multiprotein-specific mRNA and rRNA cleavage of different mutations revealed a strong correlation between the decrease in rRNA cleavage in ribosomal assembly and the degree of bone dysplasia","explanation":"Directly reports the assay and the rRNA-cleavage severity correlation."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Anauxetic_Dysplasia","model_node_id":"model:kb/disorders/Anauxetic_Dysplasia.yaml:Variant-specific RNase MRP substrate-cleavage assay","focus_node_id":"node:disorder%3AAnauxetic_Dysplasia:pathophysiology:Impaired%20rRNA%20Cleavage%20in%20Ribosome%20Assembly","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Anauxetic_dysplasia.html#pathograph","nodes":[{"id":"model:kb/disorders/Anauxetic_Dysplasia.yaml:Variant-specific RNase MRP substrate-cleavage assay","kind":"experimental_model","kind_label":"NAM model","label":"Variant-specific RNase MRP substrate-cleavage assay","description":"Variant-specific cleavage assays separate the rRNA activity that tracks skeletal severity from the mRNA activity that tracks CHH-like hair, immune, and haematologic manifestations. The assays support substrate-specific genotype-phenotype correlation but do not model growth-plate architecture.","url":"https://dismech.monarchinitiative.org/pages/disorders/Anauxetic_dysplasia.html#experimental-model-variant-specific-rnase-mrp-substrate-cleavage-assay","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAnauxetic_Dysplasia:pathophysiology:Impaired%20rRNA%20Cleavage%20in%20Ribosome%20Assembly","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired rRNA Cleavage in Ribosome Assembly","description":"The first of the two substrate arms. RNase MRP participates in ribosomal RNA processing during ribosome assembly, and the magnitude of the rRNA cleavage defect correlates directly with the degree of bone dysplasia. Anauxetic dysplasia sits at the severe end because its allele combinations produce the greatest loss of this specific activity. The ribosomopathy label is the conventional reading of that correlation, but it is contested; see the knowledge gap attached to this node.","url":"https://dismech.monarchinitiative.org/pages/disorders/Anauxetic_dysplasia.html#pathophysiology-impaired-rrna-cleavage-in-ribosome-assembly","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAnauxetic_Dysplasia:pathophysiology:Growth%20Plate%20Chondrocyte%20Differentiation%20Failure","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Growth Plate Chondrocyte Differentiation Failure","description":"Chondrocytes in the proliferative zone of the growth plate are among the most biosynthetically demanding cells in the developing skeleton, which is why a generalized ribosome assembly defect strikes them hardest. Experimentally the step most affected is hypertrophic differentiation rather than proliferation alone, and RNase MRP is itself expressed in the growth plate with expression tracking chondrocyte hypertrophy. The result is metaphyseal dysplasia and a failure of endochondral bone elongation that is already evident at birth.","url":"https://dismech.monarchinitiative.org/pages/disorders/Anauxetic_dysplasia.html#pathophysiology-growth-plate-chondrocyte-differentiation-failure","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAnauxetic_Dysplasia:pathophysiology:RNase%20MRP%20Complex%20Loss%20of%20Function","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"RNase MRP Complex Loss of Function","description":"RMRP encodes the untranslated RNA component of RNase MRP, a ribonucleoprotein endoribonuclease. Pathogenic variants either alter evolutionarily conserved nucleotides or disrupt the secondary structure by mispairing within stem regions, so the lesion is one of RNA folding and catalysis rather than of a protein coding sequence. The genetically distinct forms hit protein members of the same complex (POP1) or an interacting nucleolar partner (NEPRO), which is why they converge on one phenotype.","url":"https://dismech.monarchinitiative.org/pages/disorders/Anauxetic_dysplasia.html#pathophysiology-rnase-mrp-complex-loss-of-function","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Anauxetic_Dysplasia.yaml:Variant-specific RNase MRP substrate-cleavage assay","source_id":"model:kb/disorders/Anauxetic_Dysplasia.yaml:Variant-specific RNase MRP substrate-cleavage 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hypertrophy.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3AAnauxetic_Dysplasia:0:0","source_id":"node:disorder%3AAnauxetic_Dysplasia:pathophysiology:RNase%20MRP%20Complex%20Loss%20of%20Function","target_id":"node:disorder%3AAnauxetic_Dysplasia:pathophysiology:Impaired%20rRNA%20Cleavage%20in%20Ribosome%20Assembly","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[0]","label":"Causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":null,"causal_link_type_label":null,"description":"Loss of RNase MRP activity on its ribosomal RNA substrate compromises ribosome biogenesis.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0}]}},{"target":"mRNA Cleavage-Dependent Spectrum 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spectrum.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"reduced mRNA cleavage, and thus cell-cycle impairment, predicts the presence of hair hypoplasia, immunodeficiency, and hematological abnormalities and thus increased cancer risk","explanation":"Directly reports the substrate-specific extraskeletal correlation."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Anauxetic_Dysplasia","model_node_id":"model:kb/disorders/Anauxetic_Dysplasia.yaml:Variant-specific RNase MRP substrate-cleavage assay","focus_node_id":"node:disorder%3AAnauxetic_Dysplasia:pathophysiology:mRNA%20Cleavage-Dependent%20Spectrum%20Modulation","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Anauxetic_dysplasia.html#pathograph","nodes":[{"id":"model:kb/disorders/Anauxetic_Dysplasia.yaml:Variant-specific RNase MRP substrate-cleavage assay","kind":"experimental_model","kind_label":"NAM 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Reduced cleavage of RNase MRP messenger-RNA targets impairs cell-cycle regulation, and the degree of that impairment predicts hair hypoplasia, immunodeficiency and haematological abnormality rather than bone severity. Pure ANXD can therefore combine profound skeletal dysplasia with relative preservation of these extraskeletal systems. The concrete substrate is Cyclin B2 mRNA, cleaved at the end of mitosis.","url":"https://dismech.monarchinitiative.org/pages/disorders/Anauxetic_dysplasia.html#pathophysiology-mrna-cleavage-dependent-spectrum-modulation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AAnauxetic_Dysplasia:pathophysiology:Conditional%20Immune%20and%20Haematopoietic%20Spectrum%20Involvement","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Conditional Immune and Haematopoietic Spectrum Involvement","description":"Immunodeficiency, defective erythrogenesis, and malignancy risk belong to the CHH-AD spectrum and track the messenger-RNA-cleavage arm. 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This is a true null state rather than a hypomorphic or dominant-negative one, and it explains why two distinct alleles converge on a shared molecular consequence.","url":"https://dismech.monarchinitiative.org/pages/disorders/Neurodevelopmental_Disorder_with_Hypotonia,_Feeding_Difficulties,_Facial_Dysmorphism,_and_Brain_Abnormalities.html#pathophysiology-complete-loss-of-wbp4-protein","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ANeurodevelopmental_Disorder_with_Hypotonia_Feeding_Difficulties_Facial_Dysmorphism_and_Brain_Abnormalities:pathophysiology:Biallelic%20WBP4%20Loss-of-Function%20Variants","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Biallelic WBP4 Loss-of-Function Variants","description":"Five different homozygous loss-of-function alleles have been reported across eight families, comprising frameshift and other truncating variants plus a multi-exon deletion. 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All alleles are absent or present at extremely low frequency in population databases.","url":"https://dismech.monarchinitiative.org/pages/disorders/Neurodevelopmental_Disorder_with_Hypotonia,_Feeding_Difficulties,_Facial_Dysmorphism,_and_Brain_Abnormalities.html#pathophysiology-biallelic-wbp4-loss-of-function-variants","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3ANeurodevelopmental_Disorder_with_Hypotonia_Feeding_Difficulties_Facial_Dysmorphism_and_Brain_Abnormalities:pathophysiology:Loss%20of%20WBP4%20Restraint%20on%20SNRNP200%20in%20the%20Spliceosomal%20B%20Complex","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Loss of WBP4 Restraint on SNRNP200 in the Spliceosomal B Complex","description":"WBP4 (FBP21) is a 376-amino-acid protein with a zinc finger motif and two tandem WW domains that is present exclusively in the spliceosomal B complex, acting immediately before catalytic activation. 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Progressive kyphoscoliosis and joint contractures appear in survivors.","url":"https://dismech.monarchinitiative.org/pages/disorders/Wiedemann-Rautenstrauch_Syndrome.html#pathophysiology-skeletal-undergrowth-osteopenia-and-craniofacial-dysmorphogenesis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"}],"edges":[{"id":"model-link:0:model:kb/disorders/Wiedemann-Rautenstrauch_Syndrome.yaml:WRS bone-marrow-derived progenitor differentiation culture","source_id":"model:kb/disorders/Wiedemann-Rautenstrauch_Syndrome.yaml:WRS bone-marrow-derived progenitor differentiation culture","target_id":"node:disorder%3AWiedemann-Rautenstrauch_Syndrome:pathophysiology:Impaired%20Mesenchymal%20Progenitor%20Proliferation%20and%20Differentiation","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"The only direct measurement of progenitor differentiation capacity in WRS.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AWiedemann-Rautenstrauch_Syndrome:5:0","source_id":"node:disorder%3AWiedemann-Rautenstrauch_Syndrome:pathophysiology:Impaired%20Mesenchymal%20Progenitor%20Proliferation%20and%20Differentiation","target_id":"node:disorder%3AWiedemann-Rautenstrauch_Syndrome:pathophysiology:Generalized%20Subcutaneous%20Lipoatrophy%20with%20Localized%20Fat%20Pads","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[5].downstream[0]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"Inferred failure of adipose progenitors to form or maintain fat depots. The paradoxical persistence of gluteal and labial pads is unexplained.","intermediate_mechanisms":[],"hypothesis_groups":["canonical_pol3_partial_lof"],"evidence_count":0},{"id":"causal:disorder%3AWiedemann-Rautenstrauch_Syndrome:5:2","source_id":"node:disorder%3AWiedemann-Rautenstrauch_Syndrome:pathophysiology:Impaired%20Mesenchymal%20Progenitor%20Proliferation%20and%20Differentiation","target_id":"node:disorder%3AWiedemann-Rautenstrauch_Syndrome:pathophysiology:Prenatal%20and%20Postnatal%20Growth%20Failure","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[5].downstream[2]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"Global reduction in progenitor proliferation is the assumed basis of the growth failure that begins in utero and persists despite adequate caloric intake.","intermediate_mechanisms":[],"hypothesis_groups":["canonical_pol3_partial_lof"],"evidence_count":0},{"id":"causal:disorder%3AWiedemann-Rautenstrauch_Syndrome:5:1","source_id":"node:disorder%3AWiedemann-Rautenstrauch_Syndrome:pathophysiology:Impaired%20Mesenchymal%20Progenitor%20Proliferation%20and%20Differentiation","target_id":"node:disorder%3AWiedemann-Rautenstrauch_Syndrome:pathophysiology:Skeletal%20Undergrowth%2C%20Osteopenia%20and%20Craniofacial%20Dysmorphogenesis","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[5].downstream[1]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"Reduced osteoblastic and chondrogenic differentiation is the proposed route to undermineralised bone, persistently open fontanelles and the craniofacial disproportion.","intermediate_mechanisms":[],"hypothesis_groups":["canonical_pol3_partial_lof"],"evidence_count":0},{"id":"causal:disorder%3AWiedemann-Rautenstrauch_Syndrome:4:0","source_id":"node:disorder%3AWiedemann-Rautenstrauch_Syndrome:pathophysiology:Nucleolar%20Disruption%2C%20p53%20Activation%20and%20Premature%20Senescence","target_id":"node:disorder%3AWiedemann-Rautenstrauch_Syndrome:pathophysiology:Impaired%20Mesenchymal%20Progenitor%20Proliferation%20and%20Differentiation","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[4].downstream[0]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"Hypothesised route in which p53-driven senescence of progenitors exhausts the mesenchymal pools needed for adipose, bone and cartilage formation. 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system.","Reports the osteoblastic readout.","Reports the chondrocyte and hematopoietic readouts."],"evidence_status":"Evidence recorded","metadata_completeness":60,"metadata_present":["Model category","Organism","Cell type","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Anatomy","Cell source","Culture system"],"dataset_context":"None recorded in same 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Direct quantification of Pol III transcripts in WRS cells has not been published; the reduction of tRNA and BC200 levels has been shown in cell lines and fibroblasts carrying leukodystrophy-associated POLR3A alleles, so this step is extrapolated from the allelic disorder.","url":"https://dismech.monarchinitiative.org/pages/disorders/Wiedemann-Rautenstrauch_Syndrome.html#pathophysiology-rna-polymerase-iii-transcriptional-hypofunction","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"}],"edges":[{"id":"model-link:0:model:kb/disorders/Wiedemann-Rautenstrauch_Syndrome.yaml:WRS patient-derived induced pluripotent stem cells","source_id":"model:kb/disorders/Wiedemann-Rautenstrauch_Syndrome.yaml:WRS patient-derived induced pluripotent stem cells","target_id":"node:disorder%3AWiedemann-Rautenstrauch_Syndrome:pathophysiology:Nucleolar%20Disruption%2C%20p53%20Activation%20and%20Premature%20Senescence","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Partially Recapitulates","directed":false,"relationship":"PARTIALLY_RECAPITULATES","fidelity":"LOW","causal_link_type":null,"causal_link_type_label":null,"description":"Reproduces nucleolar abnormality and adds TERC sequestration, but in a pluripotent state that overexpresses POLR3A.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AWiedemann-Rautenstrauch_Syndrome:4:0","source_id":"node:disorder%3AWiedemann-Rautenstrauch_Syndrome:pathophysiology:Nucleolar%20Disruption%2C%20p53%20Activation%20and%20Premature%20Senescence","target_id":"node:disorder%3AWiedemann-Rautenstrauch_Syndrome:pathophysiology:Impaired%20Mesenchymal%20Progenitor%20Proliferation%20and%20Differentiation","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[4].downstream[0]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"Hypothesised route in which p53-driven senescence of progenitors exhausts the mesenchymal pools needed for adipose, bone and cartilage formation. 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Wiedemann-Rautenstrauch Syndrome (WRS), which is caused by bi-allelic pathogenic mutations of the RNA polymerase III subunit A gene (POLR3A)","explanation":"Establishes the derivation and genotype of this patient iPSC model."},{"reference":"PMID:41081995","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41081995","reference_title":"POLR3A mutations cause nucleolus abnormalities and aberrant telomerase RNA metabolism in induced pluripotent stem cells from Wiedemann-Rautenstrauch premature aging syndrome patient.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Whereas lamin A is downregulated in iPSCs, allowing for regeneration of HGPS iPSCs, we found that POLR3A is upregulated during reprogramming.","explanation":"Explains why the model exaggerates mutant POLR3A expression."},{"reference":"PMID:41081995","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41081995","reference_title":"POLR3A mutations cause nucleolus abnormalities and aberrant telomerase RNA metabolism in induced pluripotent stem cells from Wiedemann-Rautenstrauch premature aging syndrome patient.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Enhanced expression of mutant POLR3A in WRS iPSCs led to nucleolus abnormalities and telomerase RNA component (TERC) sequestration in the nucleoli in WRS iPSCs.","explanation":"Reports the nucleolar and TERC measurement."}],"evidence_text":["using a non-integrative episomal approach we reprogrammed iPSCs from cells of a patient suffering from Wiedemann-Rautenstrauch Syndrome (WRS), which is caused by bi-allelic pathogenic mutations of the RNA polymerase III subunit A gene (POLR3A)","Whereas lamin A is downregulated in iPSCs, allowing for regeneration of HGPS iPSCs, we found that POLR3A is upregulated during reprogramming.","Enhanced expression of mutant POLR3A in WRS iPSCs led to nucleolus abnormalities and telomerase RNA component (TERC) sequestration in the nucleoli in WRS iPSCs.","Establishes the derivation and genotype of 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How much this branch contributes to the human neurodevelopmental phenotype remains uncertain.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Wiedemann-Steiner_Syndrome.html#pathophysiology-centrosome-dysfunction-and-impaired-microtubule-nucleation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":"PROVISIONAL","mechanism_confidence_label":"Provisional"},{"id":"node:disorder%3AWiedemann-Steiner_Syndrome:phenotype:Global%20Developmental%20Delay","kind":"phenotype","kind_label":"Phenotype","label":"Global Developmental Delay","description":"Developmental delay was reported in 90% of affected children in a physical-therapy review, while developmental delay or intellectual disability combined was reported in 97% of the largest cohort. 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It is the cleanest available separation of the allele's catalytic effect from everything else about a patient cell, and it is what first showed that a nuclear-coded subunit participates in the reaction with ubiquinone.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_3.html#experimental-model-yarrowia-lipolytica-complex-i-carrying-the-psst-v122m-patient-substitution","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_3:pathophysiology:Defective%20NADH-to-Ubiquinone%20Electron%20Transfer","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Defective NADH-to-Ubiquinone Electron Transfer","description":"The measured biochemical endpoint: reduced NADH:ubiquinone oxidoreductase activity, with the rest of the respiratory chain intact. Reconstructing the patient V122M substitution in the homologous subunit of Yarrowia lipolytica halves Vmax, and the same experiment records altered Km for n-decyl-ubiquinone and altered I50 for hydrophobic complex I inhibitors - both quinone-site readouts. The authors take this as evidence that nuclear-coded subunits, not only the hydrophobic mitochondrially coded ones, participate in the reaction with ubiquinone, which is precisely the claim the upstream Q-module node makes structurally.\nThe fibroblast panel that includes an NDUFS7 line adds the amount-versus-activity decomposition: in controls the ratio of complex I activity to complex I amount is one, and in patients it is below one, so the enzyme that does assemble is intrinsically less catalytically competent. The deficiency is quantitative and qualitative at once, which is what a core Q-module subunit defect predicts.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_3.html#pathophysiology-defective-nadh-to-ubiquinone-electron-transfer","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_3:pathophysiology:Impaired%20Complex%20I%20Assembly%20and%20Biogenesis","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Complex I Assembly and Biogenesis","description":"The second, separable arm of the lesion. Native analysis of respiratory-chain complexes in the cryptic-exon patient showed a marked decrease of fully assembled complex I while the other complexes were unaltered - the definition of an isolated, assembly-level complex I defect. The Finnish siblings with the c.16+5G>A allele were likewise characterised as having an isolated complex I assembly defect on blue native PAGE.\nNDUFS7 enters the assembly pathway early: complexome profiling places NDUFAF8, together with NDUFAF5, at the early stabilisation of NDUFS7, which is why a defect in this subunit stalls Q-module maturation rather than removing a late decorative step.\nA negative observation from an unrelated study is worth recording here because it is specific to this gene: in patient fibroblasts carrying an NDUFS7 mutation, the assembly factor NDUFAF2 was not detected on complex I at all, whereas in NDUFS1- and NDUFV1-mutant cells it remained attached to the 830-kDa subcomplex. Whatever intermediate NDUFAF2 normally holds is not formed or not retained when NDUFS7 is defective.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_3.html#pathophysiology-impaired-complex-i-assembly-and-biogenesis","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_3:pathophysiology:Isolated%20Complex%20I%20Deficiency%20and%20Bioenergetic%20Failure","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Isolated Complex I Deficiency and Bioenergetic Failure","description":"Cellular oxidative phosphorylation capacity falls and reactive oxygen species rise. Both arms of the module node are evidenced here rather than only one: an NDUFS7-containing fibroblast panel shows raised ROS alongside reduced complex I activity and amount, and an engineered NDUFS7 mutation in HEK293T cells produces reduced proliferation, elevated cell death and increased susceptibility to oxidative stress.\nTwo caveats a curator should carry forward. First, cultured cells hide the deficit: complex I-deficient cells upregulate glycolysis to replace the lost mitochondrial ATP, and that adaptation masks other consequences - which is why the NDUFS7 line only dies when glucose is replaced by galactose in a pyruvate-free medium. The clinical counterpart is decompensation under catabolic stress. Second, the cells are not defenceless: upregulated SLC7A11 imports cystine and raises glutathione, and that response measurably limits the cell death caused by NDUFS7 deficiency.\nConformance note: the module's upstream node - age-related mitochondrial damage and mtDNA mutation - does not apply to a primary nuclear-gene subunit defect, so conformance is declared at this node alone.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_3.html#pathophysiology-isolated-complex-i-deficiency-and-bioenergetic-failure","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_3:pathophysiology:Loss%20of%20Q-Module%20Integrity%20at%20the%20Cluster%20N2%20and%20CoQ%20Binding%20Site","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Loss of Q-Module Integrity at the Cluster N2 and CoQ Binding Site","description":"What NDUFS7/PSST actually does, and the reason a missense allele here is not equivalent to losing an accessory subunit. Complex I transfers two electrons from NADH to FMN and then one at a time along a ninety-five-angstrom chain of seven conserved iron-sulfur clusters to a quinone-binding site at the interface with the membrane domain. That site is unusually long, narrow and enclosed, and the quinone headgroup binds at its deep end, immediately adjacent to cluster N2 - the cluster that donates the electrons. NDUFS7 sits at the junction between the peripheral and membrane arms and contributes to forming that site.\nThe functional consequence has been isolated experimentally. Mutating conserved residues in the PSST loop that faces the roughly thirty-angstrom Q-binding tunnel causes a drastic decrease in quinone reductase activity despite full assembly of the complex, and molecular dynamics of the arginine variants shows the bound quinone being ejected from the site near N2. This is a catalytic lesion, separable from the assembly lesion that the truncating alleles produce.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_3.html#pathophysiology-loss-of-q-module-integrity-at-the-cluster-n2-and-coq-binding-site","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"}],"edges":[{"id":"model-link:0:model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_3.yaml:Yarrowia lipolytica complex I carrying the PSST V122M patient substitution","source_id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_3.yaml:Yarrowia lipolytica complex I carrying the PSST V122M patient substitution","target_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_3:pathophysiology:Defective%20NADH-to-Ubiquinone%20Electron%20Transfer","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Recapitulates","directed":false,"relationship":"RECAPITULATES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"Reconstructing the patient allele in a yeast complex I halves Vmax and shifts the Km for decyl-ubiquinone, isolating a quinone-reaction defect.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_3:3:0","source_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_3:pathophysiology:Defective%20NADH-to-Ubiquinone%20Electron%20Transfer","target_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_3:pathophysiology:Isolated%20Complex%20I%20Deficiency%20and%20Bioenergetic%20Failure","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[3].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Reduced electron flux into the ubiquinone pool lowers proton pumping and oxidative phosphorylation capacity.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_3:2:0","source_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_3:pathophysiology:Impaired%20Complex%20I%20Assembly%20and%20Biogenesis","target_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_3:pathophysiology:Defective%20NADH-to-Ubiquinone%20Electron%20Transfer","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Less assembled enzyme means less NADH:ubiquinone oxidoreductase capacity, independently of any catalytic defect in the enzyme that does assemble.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0},{"id":"causal:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_3:1:0","source_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_3:pathophysiology:Loss%20of%20Q-Module%20Integrity%20at%20the%20Cluster%20N2%20and%20CoQ%20Binding%20Site","target_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_3:pathophysiology:Defective%20NADH-to-Ubiquinone%20Electron%20Transfer","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"A compromised quinone site adjacent to the terminal cluster is a compromised final electron-transfer step.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":0}]}}],"mechanism_names":["Defective 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n-decyl-ubiquinone"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:11004438","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/11004438","reference_title":"Application of the obligate aerobic yeast Yarrowia lipolytica as a eucaryotic model to analyse Leigh syndrome mutations in the complex I core subunits PSST and TYKY.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We have used the obligate aerobic yeast Yarrowia lipolytica to reconstruct and analyse three missense mutations in the nuclear coded subunits homologous to bovine TYKY and PSST of mitochondrial complex I","explanation":"Establishes what the model is and that it carries the patient substitutions, which is what makes it informative for this node."},{"reference":"PMID:11004438","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/11004438","reference_title":"Application of the obligate aerobic yeast Yarrowia lipolytica as a eucaryotic model to analyse Leigh syndrome mutations in the complex I core subunits PSST and TYKY.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Mitochondrial membranes from Y. lipolytica strains carrying any of the three point mutations exhibited similar complex I defects, with V(max) being reduced by about 50%.","explanation":"The kinetic measurement behind this readout."},{"reference":"PMID:11004438","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/11004438","reference_title":"Application of the obligate aerobic yeast Yarrowia lipolytica as a eucaryotic model to analyse Leigh syndrome mutations in the complex I core subunits PSST and TYKY.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"In addition changes in the K(m) for n-decyl-ubiquinone and I(50) for hydrophobic complex I inhibitors were observed","explanation":"The quinone-binding measurements behind this readout."}],"evidence_text":["We have used the obligate aerobic yeast Yarrowia lipolytica to reconstruct and analyse three missense mutations in the nuclear coded subunits homologous to bovine TYKY and PSST of mitochondrial complex I","Mitochondrial membranes from Y. lipolytica strains carrying any of the three point mutations exhibited similar complex I defects, with V(max) being reduced by about 50%.","In addition changes in the K(m) for n-decyl-ubiquinone and I(50) for hydrophobic complex I inhibitors were observed","Establishes what the model is and that it carries the patient substitutions, which is what makes it informative for this node.","The kinetic measurement behind this readout.","The quinone-binding measurements behind this readout."],"evidence_status":"Evidence recorded","metadata_completeness":30,"metadata_present":["Model category","Modeled 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Its consequence was tested by reconstructing the resulting altered C-terminus in Ind1, the NUBPL homologue of the respiratory yeast Yarrowia lipolytica, which unlike Saccharomyces has a complete complex I.","notes":null,"context_id":"disorder:Mitochondrial_Complex_I_Deficiency_Nuclear_Type_21","context_kind":"Disorder","disease_name":"Mitochondrial Complex I Deficiency Nuclear Type 21","disease_synonyms":["MC1DN21","NUBPL-related mitochondrial disease","NUBPL deficiency","complex I deficiency due to NUBPL mutation"],"disease_term":{"id":"MONDO:0032625","label":"mitochondrial complex I deficiency, nuclear type 21","display_label":"mitochondrial complex I deficiency, nuclear type 21","url":"http://purl.obolibrary.org/obo/MONDO_0032625"},"experimental_model_type":"OTHER","experimental_model_type_label":"Other","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":null,"source_category":null,"culture_system":null,"publication":"PMID:23828044","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/23828044","mechanisms":[{"target":"NUBPL Loss of Function","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_21.html#pathophysiology-nubpl-loss-of-function","relationship":"RECAPITULATES","relationship_label":"Recapitulates","fidelity":"MODERATE","fidelity_label":"Moderate","description":"Establishes that the altered C-terminus destabilises the protein without affecting transcript level, and that this alone is enough to cause a null-like complex I phenotype.","limitations":"A yeast homologue, not the human protein, and the construct reproduces the predicted altered C-terminus rather than the human splice event itself. It therefore tests the consequence of the predicted protein change, not that human cells actually make that protein.","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[],"biological_processes":[],"pathways":[],"genes":[{"id":"hgnc:20278","label":"NUBPL","display_label":"NUBPL","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/20278"}],"chemicals":[],"readouts":[{"name":"Ind1 protein level","description":null,"target":"NUBPL Loss of Function","direction":"DECREASED","interpretation":"Locates the effect at the protein rather than the transcript level.","biological_processes":[],"phenotypes":[],"biomarkers":[],"assays":[],"evidence":[{"reference":"PMID:23828044","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/23828044","reference_title":"Insights into the pathogenic character of a common NUBPL branch-site mutation associated with mitochondrial disease and complex I deficiency using a yeast model.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"We demonstrate that the altered sequence did not affect IND1 mRNA stability, yet it led to a decrease in Ind1 protein level.","explanation":"The measurement separating protein instability from transcript loss."}],"notes":null}],"evidence":[{"reference":"PMID:23828044","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/23828044","reference_title":"Insights into the pathogenic character of a common NUBPL branch-site mutation associated with mitochondrial disease and complex I deficiency using a yeast model.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"The presented data confirms the deleterious impact of the altered C-terminus resulting from the branch-site mutation.","explanation":"The authors' conclusion that this model settles the pathogenicity question the allele frequency had raised."},{"reference":"PMID:23828044","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/23828044","reference_title":"Insights into the pathogenic character of a common NUBPL branch-site mutation associated with mitochondrial disease and complex I deficiency using a yeast model.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"We demonstrate that the altered sequence did not affect IND1 mRNA stability, yet it led to a decrease in Ind1 protein level.","explanation":"The measurement separating protein instability from transcript loss."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Mitochondrial_Complex_I_Deficiency_Nuclear_Type_21","model_node_id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_21.yaml:Yarrowia lipolytica Ind1 carrying the branch-site-derived altered C-terminus","focus_node_id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_21:pathophysiology:NUBPL%20Loss%20of%20Function","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_21.html#pathograph","nodes":[{"id":"model:kb/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_21.yaml:Yarrowia lipolytica Ind1 carrying the branch-site-derived altered C-terminus","kind":"experimental_model","kind_label":"NAM model","label":"Yarrowia lipolytica Ind1 carrying the branch-site-derived altered C-terminus","description":"The human NUBPL branch-site variant c.815-27T>C is present in roughly 1.2% of European haplotypes, far too common to be assumed pathogenic. 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Not every missense allele is equally damaging - p.Leu104Pro impaired complex I function in the yeast model while p.Val182Ala did not.","url":"https://dismech.monarchinitiative.org/pages/disorders/Mitochondrial_Complex_I_Deficiency_Nuclear_Type_21.html#pathophysiology-nubpl-loss-of-function","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":"ESTABLISHED","mechanism_confidence_label":"Established"},{"id":"node:disorder%3AMitochondrial_Complex_I_Deficiency_Nuclear_Type_21:pathophysiology:Impaired%20Iron-Sulfur%20Cluster%20Delivery%20to%20the%20Complex%20I%20Peripheral%20Arm","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Iron-Sulfur Cluster Delivery to the Complex I Peripheral Arm","description":"NUBPL is an iron-sulfur cluster assembly factor for complex I. 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transformants (Figure 5A and Table 3).","explanation":"Human Arg20His expressed in yeast retains partial activity relative to wild-type complementation."},{"reference":"PMID:26669719","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/26669719","reference_title":"Mitochondrial disease genes COA6, COX6B and SCO2 have overlapping roles in COX2 biogenesis.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"In order to place Coa6 in the Cox2 copper delivery pathway, we performed a comprehensive genetic epistasis analysis in the yeast Saccharomyces cerevisiae and found that simultaneous deletion of Coa6 and Sco2, a mitochondrial copper metallochaperone, or Coa6 and Cox12/COX6B, a structural subunit of CcO, completely abrogates Cox2 biogenesis.","explanation":"The double-deletion experiment supports overlapping Cox12/Coa6 functions without establishing direct human COX6B1 copper transfer."}],"evidence_text":["Cox12 with arginine 17 residue substituted by histidine (R17H) or 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Examples: HepG2, A549, Caco-2, etc.","namo_docs_url":"https://monarch-initiative.github.io/namo/elements/CellLineModel/","namo_ontology_url":"https://w3id.org/monarch-initiative/namo/CellLineModel","namo_mapping_basis":"Safe mapping from DisMech category","namo_class_in_schema":true,"namo_schema_status":"Defined in NAMO schema used for this build","modality":"Cellular system","organism":null,"organism_label":null,"model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[],"linked_anatomy_labels":[],"anatomy":[],"anatomy_labels":[],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[],"linked_cell_type_labels":[],"cell_types":[],"cell_type_labels":[],"conditions":[],"cell_source":null,"source_category":"Immortalized / cell line","culture_system":null,"publication":null,"publication_url":null,"mechanisms":[{"target":"Impaired ZFX-Dependent Transcriptional Activation at CpG Island Promoters","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Intellectual_Developmental_Disorder,_X-Linked,_Syndromic_37.html#pathophysiology-impaired-zfx-dependent-transcriptional-activation-at-cpg-island-promoters","relationship":"MEASURES","relationship_label":"Measures","fidelity":"MODERATE","fidelity_label":"Moderate","description":"Quantifies the transcriptomic consequence of losing ZFX and localises DNA-binding function to zinc fingers 11-13.\n","limitations":"An immortalised kidney-derived cell line, not a neural or parathyroid context, and complete bi-allelic knockout rather than the partial dosage reduction that a heterozygous patient sustains.\n","biological_scale":"MOLECULAR","anatomy":[],"cell_types":[],"biological_processes":[{"id":"GO:0045944","label":"positive regulation of transcription by RNA polymerase II","display_label":"positive regulation of transcription by RNA polymerase II","url":"http://purl.obolibrary.org/obo/GO_0045944"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[],"evidence":[{"reference":"PMID:32406922","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/32406922","reference_title":"Characterization of the ZFX family of transcription factors that bind downstream of the start site of CpG island promoters.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We found that loss of either ZFX or ZNF711 reduced cell growth and that the double knockout cells have major defects in proliferation.","explanation":"The proliferation phenotype of ZFX loss in human cells."}],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Intellectual_Developmental_Disorder_X-Linked_Syndromic_37","model_node_id":"model:kb/disorders/Intellectual_Developmental_Disorder_X-Linked_Syndromic_37.yaml:ZFX and ZNF711 CRISPR knockout HEK293T cells","focus_node_id":"node:disorder%3AIntellectual_Developmental_Disorder_X-Linked_Syndromic_37:pathophysiology:Impaired%20ZFX-Dependent%20Transcriptional%20Activation%20at%20CpG%20Island%20Promoters","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Intellectual_Developmental_Disorder,_X-Linked,_Syndromic_37.html#pathograph","nodes":[{"id":"model:kb/disorders/Intellectual_Developmental_Disorder_X-Linked_Syndromic_37.yaml:ZFX and ZNF711 CRISPR knockout HEK293T cells","kind":"experimental_model","kind_label":"NAM model","label":"ZFX and ZNF711 CRISPR knockout HEK293T cells","description":"Bi-allelic CRISPR knockouts of ZFX and/or ZNF711 in female HEK293T cells, used to establish the scale of transcriptome dysregulation caused by loss of these factors and to map the domains required for DNA binding and transactivation.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Intellectual_Developmental_Disorder,_X-Linked,_Syndromic_37.html#experimental-model-zfx-and-znf711-crispr-knockout-hek293t-cells","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AIntellectual_Developmental_Disorder_X-Linked_Syndromic_37:pathophysiology:Impaired%20ZFX-Dependent%20Transcriptional%20Activation%20at%20CpG%20Island%20Promoters","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired ZFX-Dependent Transcriptional Activation at CpG Island Promoters","description":"The convergent molecular node. ZFX binds a short motif roughly 200-250 bp downstream of the transcription start site at the majority of active CpG island promoters - an unusual, architecturally defined binding position inside the transcribed region rather than upstream - and acts there as an activator. Genes whose promoters ZFX occupies are expressed at higher levels, and knockdown reduces their expression. Both the truncating and the missense allele classes converge on degraded or mis-specified output from this promoter-proximal activator function.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Intellectual_Developmental_Disorder,_X-Linked,_Syndromic_37.html#pathophysiology-impaired-zfx-dependent-transcriptional-activation-at-cpg-island-promoters","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AIntellectual_Developmental_Disorder_X-Linked_Syndromic_37:pathophysiology:Disrupted%20Craniofacial%20Patterning%20and%20Congenital%20Anomaly%20Formation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Disrupted Craniofacial Patterning and Congenital Anomaly Formation","description":"The extra-neural developmental consequence: a recurrent and clinically recognisable facial gestalt present in every reported subject of the founding cohort - thickened and medially broadened eyebrows, altered facial shape, external eye anomalies, a smooth and/or long philtrum and ear anomalies - together with a variable burden of congenital anomalies. This node deliberately carries no mechanistic annotation beyond the clinical observation: no study has examined cranial neural crest, pharyngeal-arch patterning, or any other craniofacial developmental programme in ZFX deficiency, so the route from the transcriptional defect to the gestalt is entirely unexamined. That unexamined route is recorded as the `zfx_craniofacial_route_gap` discussion; it is a reason to draw the incoming edge as INDIRECT_UNKNOWN_INTERMEDIATES, not a reason to omit it - that ZFX variants produce this gestalt is the disease definition, and only the mechanism is unknown.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Intellectual_Developmental_Disorder,_X-Linked,_Syndromic_37.html#pathophysiology-disrupted-craniofacial-patterning-and-congenital-anomaly-formation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AIntellectual_Developmental_Disorder_X-Linked_Syndromic_37:pathophysiology:Escape%20of%20ZFX%20from%20X%20Inactivation","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Escape of ZFX from X Inactivation","description":"ZFX is one of the few human X-linked genes that escape X inactivation, so it is transcribed from both the active and the inactive X in females. This is a constitutive property of the locus rather than a disease event, and it is modelled here because it is what determines the dosage consequence of a heterozygous allele: a female carrier has a uniform partial reduction in ZFX activity in every cell rather than a mosaic of wild-type and mutant cells, which is why females are genuinely affected rather than silent carriers.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Intellectual_Developmental_Disorder,_X-Linked,_Syndromic_37.html#pathophysiology-escape-of-zfx-from-x-inactivation","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AIntellectual_Developmental_Disorder_X-Linked_Syndromic_37:pathophysiology:Germline%20ZFX%20Truncating%20Variant","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Germline ZFX Truncating Variant","description":"Frameshift and nonsense variants distributed across ZFX, accounting for seven of the eleven variants in the founding cohort. These alleles are presumed to act by loss of function, reducing functional ZFX dosage. In a hemizygous male no functional allele remains; in a heterozygous female, because ZFX escapes X inactivation, the remaining wild-type allele is expressed in every cell but cannot be up-regulated to compensate, giving a genuine partial dosage reduction rather than cellular mosaicism.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Intellectual_Developmental_Disorder,_X-Linked,_Syndromic_37.html#pathophysiology-germline-zfx-truncating-variant","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AIntellectual_Developmental_Disorder_X-Linked_Syndromic_37:pathophysiology:Germline%20ZFX%20Zinc-Finger%20Missense%20Variant","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Germline ZFX Zinc-Finger Missense Variant","description":"Missense variants affecting the C2H2 zinc-finger DNA-binding region of ZFX, which in the founding cohort accounted for four variants but eleven of the eighteen subjects. This allele class is separated from the truncating class because its reported functional consequence is altered rather than simply absent transcriptional output, and because every founding-cohort family with hyperparathyroidism carried a missense allele. It is NOT curated as the only allele class that can produce hyperparathyroidism: a later series reports an in-frame insertion carrier with primary hyperparathyroidism, and the founding cohort never asserts absence of the endocrine phenotype in truncating carriers. The functionally critical fingers are the C-terminal ones: zinc fingers 11-13 are necessary and sufficient for DNA binding, and the somatic parathyroid-adenoma hotspot (R786/R787) lies in the same C-terminal zinc-finger region.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Intellectual_Developmental_Disorder,_X-Linked,_Syndromic_37.html#pathophysiology-germline-zfx-zinc-finger-missense-variant","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AIntellectual_Developmental_Disorder_X-Linked_Syndromic_37:pathophysiology:Impaired%20Stem%20and%20Progenitor%20Cell%20Self-Renewal","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired Stem and Progenitor Cell Self-Renewal","description":"In model systems, loss of ZFX selectively impairs self-renewal while leaving differentiation capacity intact, with increased apoptosis and stem-cell-specific up-regulation of stress-inducible genes. The requirement is conserved to human embryonic stem cells, where ZFX behaves as a rheostat setting the balance between self-renewal and differentiation. Extension of this to neural progenitors in the developing human brain is INFERENCE, not observation - no patient-tissue or neural-progenitor data exist for MRXS37, which is recorded as a knowledge gap below. The cell types annotated on this node are therefore deliberately the ones actually assayed, embryonic and haematopoietic stem cells, and NOT neural stem cells, so that the pathograph and anything exported from it do not assert a neural-progenitor claim this entry's own prose declines to make.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Intellectual_Developmental_Disorder,_X-Linked,_Syndromic_37.html#pathophysiology-impaired-stem-and-progenitor-cell-self-renewal","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AIntellectual_Developmental_Disorder_X-Linked_Syndromic_37:pathophysiology:Increased%20RNA%20Polymerase%20II%20Promoter-Proximal%20Pausing","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Increased RNA Polymerase II Promoter-Proximal Pausing","description":"Reduced ZFX at target promoters increases Pol II pausing and decreases histone H4 acetylation, the two coupled readouts of the proposed mechanism: ZFX recruits H4 acetylation activity and thereby releases polymerase into productive elongation. This is the best-resolved step in the ZFX mechanism and is derived entirely from cell-line work, not from patient tissue.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Intellectual_Developmental_Disorder,_X-Linked,_Syndromic_37.html#pathophysiology-increased-rna-polymerase-ii-promoter-proximal-pausing","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Intellectual_Developmental_Disorder_X-Linked_Syndromic_37.yaml:ZFX and ZNF711 CRISPR knockout HEK293T cells","source_id":"model:kb/disorders/Intellectual_Developmental_Disorder_X-Linked_Syndromic_37.yaml:ZFX and ZNF711 CRISPR knockout HEK293T cells","target_id":"node:disorder%3AIntellectual_Developmental_Disorder_X-Linked_Syndromic_37:pathophysiology:Impaired%20ZFX-Dependent%20Transcriptional%20Activation%20at%20CpG%20Island%20Promoters","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Measures","directed":false,"relationship":"MEASURES","fidelity":"MODERATE","causal_link_type":null,"causal_link_type_label":null,"description":"Quantifies the transcriptomic consequence of losing ZFX and localises DNA-binding function to zinc fingers 11-13.\n","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AIntellectual_Developmental_Disorder_X-Linked_Syndromic_37:2:0","source_id":"node:disorder%3AIntellectual_Developmental_Disorder_X-Linked_Syndromic_37:pathophysiology:Escape%20of%20ZFX%20from%20X%20Inactivation","target_id":"node:disorder%3AIntellectual_Developmental_Disorder_X-Linked_Syndromic_37:pathophysiology:Impaired%20ZFX-Dependent%20Transcriptional%20Activation%20at%20CpG%20Island%20Promoters","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[2].downstream[0]","label":"Causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":null,"causal_link_type_label":null,"description":"MODULATING, not causing. Note the schema's `causal_link_type` encodes only directness, so it is deliberately left unset here rather than asserting a directness that would misdescribe this edge. Escape from X inactivation is a constitutive normal property of the locus and produces no disease on its own; what it does is set how a heterozygous allele translates into dosage. Because the second allele cannot be recruited by skewed inactivation, heterozygosity in a female produces a uniform partial reduction in ZFX activity rather than a mosaic.\n","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AIntellectual_Developmental_Disorder_X-Linked_Syndromic_37:0:0","source_id":"node:disorder%3AIntellectual_Developmental_Disorder_X-Linked_Syndromic_37:pathophysiology:Germline%20ZFX%20Truncating%20Variant","target_id":"node:disorder%3AIntellectual_Developmental_Disorder_X-Linked_Syndromic_37:pathophysiology:Impaired%20ZFX-Dependent%20Transcriptional%20Activation%20at%20CpG%20Island%20Promoters","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[0].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"Reduced functional ZFX protein lowers occupancy and transactivation at the CpG island promoters that ZFX normally licenses.\n","intermediate_mechanisms":[],"hypothesis_groups":["haploinsufficiency_model"],"evidence_count":2},{"id":"causal:disorder%3AIntellectual_Developmental_Disorder_X-Linked_Syndromic_37:1:0","source_id":"node:disorder%3AIntellectual_Developmental_Disorder_X-Linked_Syndromic_37:pathophysiology:Germline%20ZFX%20Zinc-Finger%20Missense%20Variant","target_id":"node:disorder%3AIntellectual_Developmental_Disorder_X-Linked_Syndromic_37:pathophysiology:Impaired%20ZFX-Dependent%20Transcriptional%20Activation%20at%20CpG%20Island%20Promoters","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[0]","label":"Causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":null,"causal_link_type_label":null,"description":"DNA-binding-domain missense alleles change the transcriptional output at ZFX target promoters relative to wild-type protein.\n","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AIntellectual_Developmental_Disorder_X-Linked_Syndromic_37:3:1","source_id":"node:disorder%3AIntellectual_Developmental_Disorder_X-Linked_Syndromic_37:pathophysiology:Impaired%20ZFX-Dependent%20Transcriptional%20Activation%20at%20CpG%20Island%20Promoters","target_id":"node:disorder%3AIntellectual_Developmental_Disorder_X-Linked_Syndromic_37:pathophysiology:Disrupted%20Craniofacial%20Patterning%20and%20Congenital%20Anomaly%20Formation","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[3].downstream[1]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"The facial gestalt and the congenital-anomaly burden follow from the same transcriptional defect as the neurodevelopmental arm. Indirect with unknown intermediates, and deliberately parented here rather than on the self-renewal node: no study has examined cranial neural crest, pharyngeal-arch patterning, or any other craniofacial developmental programme in ZFX deficiency, so no intermediate can be named and a progenitor route cannot be asserted.\n","intermediate_mechanisms":[],"hypothesis_groups":["haploinsufficiency_model"],"evidence_count":1},{"id":"causal:disorder%3AIntellectual_Developmental_Disorder_X-Linked_Syndromic_37:3:2","source_id":"node:disorder%3AIntellectual_Developmental_Disorder_X-Linked_Syndromic_37:pathophysiology:Impaired%20ZFX-Dependent%20Transcriptional%20Activation%20at%20CpG%20Island%20Promoters","target_id":"node:disorder%3AIntellectual_Developmental_Disorder_X-Linked_Syndromic_37:pathophysiology:Impaired%20Stem%20and%20Progenitor%20Cell%20Self-Renewal","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[3].downstream[2]","label":"Causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":null,"causal_link_type_label":null,"description":"Among the programmes ZFX activates is a self-renewal transcriptional module shared by embryonic and adult stem cells, so degraded ZFX output manifests cellularly as a 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of proceeding into productive elongation.\n","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1}]}}],"mechanism_names":["Impaired ZFX-Dependent Transcriptional Activation at CpG Island Promoters"],"relationships":["Measures"],"fidelities":["Moderate"],"biological_scales":["Molecular"],"system_context_sources":["Linked mechanism biological scale"],"modeled_system_labels":["Molecular"],"biological_process_terms":[{"id":"GO:0045944","label":"positive regulation of transcription by RNA polymerase II","display_label":"positive regulation of transcription by RNA polymerase II","url":"http://purl.obolibrary.org/obo/GO_0045944"}],"biological_processes":["positive regulation of transcription by RNA polymerase II"],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":[],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:32406922","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/32406922","reference_title":"Characterization of the ZFX family of transcription factors that bind downstream of the start site of CpG island promoters.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We found that loss of either ZFX or ZNF711 reduced cell growth and that the double knockout cells have major defects in proliferation.","explanation":"The proliferation phenotype of ZFX loss in human cells."}],"evidence_text":["We found that loss of either ZFX or ZNF711 reduced cell growth and that the double knockout cells have major defects in proliferation.","The proliferation phenotype of ZFX loss in human cells."],"evidence_status":"Evidence recorded","metadata_completeness":40,"metadata_present":["Model category","NAMO class","Modeled mechanism","Evidence"],"metadata_missing":["Organism","Anatomy","Cell type","Cell source","Culture system","Publication"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Intellectual_Developmental_Disorder_X-Linked_Syndromic_37.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Intellectual_Developmental_Disorder_X-Linked_Syndromic_37.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Intellectual_Developmental_Disorder,_X-Linked,_Syndromic_37.html#experimental-model-zfx-and-znf711-crispr-knockout-hek293t-cells","source_anchor":"experimental-model-zfx-and-znf711-crispr-knockout-hek293t-cells"},{"id":"model:kb/disorders/Intellectual_Developmental_Disorder_X-Linked_Syndromic_37.yaml:ZFX knockdown and overexpression in human embryonic stem cells","name":"ZFX knockdown and overexpression in human embryonic stem cells","description":"Human embryonic stem cells with ZFX knockdown or overexpression, used to test whether the self-renewal requirement identified in mouse 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Kept separate from the craniofacial and congenital-anomaly node because they are distinct developmental programmes with distinct evidence, even though both follow from the same upstream transcriptional defect.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Intellectual_Developmental_Disorder,_X-Linked,_Syndromic_37.html#pathophysiology-disrupted-neurodevelopment","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"ORGANISM","biological_scale_label":"Organism","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AIntellectual_Developmental_Disorder_X-Linked_Syndromic_37:pathophysiology:Impaired%20ZFX-Dependent%20Transcriptional%20Activation%20at%20CpG%20Island%20Promoters","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Impaired ZFX-Dependent Transcriptional Activation at CpG Island Promoters","description":"The convergent molecular node. 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Both the truncating and the missense allele classes converge on degraded or mis-specified output from this promoter-proximal activator function.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Intellectual_Developmental_Disorder,_X-Linked,_Syndromic_37.html#pathophysiology-impaired-zfx-dependent-transcriptional-activation-at-cpg-island-promoters","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AIntellectual_Developmental_Disorder_X-Linked_Syndromic_37:pathophysiology:Increased%20RNA%20Polymerase%20II%20Promoter-Proximal%20Pausing","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Increased RNA Polymerase II Promoter-Proximal Pausing","description":"Reduced ZFX at target promoters increases Pol II pausing and decreases histone H4 acetylation, the two coupled readouts of the proposed mechanism: ZFX recruits H4 acetylation activity and thereby releases polymerase into productive elongation. 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This node rests on a human stem cell model, not on patient brain tissue.","url":"https://dismech.monarchinitiative.org/pages/disorders/Intellectual_Disability,_Autosomal_Dominant_30.html#pathophysiology-impaired-cortical-progenitor-and-neuron-production","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AIntellectual_Disability_Autosomal_Dominant_30:pathophysiology:De-repression%20of%20latent%20developmental%20transcriptional%20programmes","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"De-repression of latent developmental transcriptional programmes","description":"Cortical neural stem cells lacking ZMYND11 upregulate latent developmental pathways. The same pattern appears when other chromatin-related autism risk factors are perturbed, which positions this as a shared convergent consequence of chromatin-regulator loss rather than a ZMYND11-private effect.","url":"https://dismech.monarchinitiative.org/pages/disorders/Intellectual_Disability,_Autosomal_Dominant_30.html#pathophysiology-de-repression-of-latent-developmental-transcriptional-programmes","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AIntellectual_Disability_Autosomal_Dominant_30:phenotype:Intellectual%20disability","kind":"phenotype","kind_label":"Phenotype","label":"Intellectual disability","description":"Intellectual disability is the core feature. In the epilepsy cohort it was mild to moderate in 16 of 20 individuals and severe in 4 of 20.","url":"https://dismech.monarchinitiative.org/pages/disorders/Intellectual_Disability,_Autosomal_Dominant_30.html#phenotype-intellectual-disability","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AIntellectual_Disability_Autosomal_Dominant_30:pathophysiology:Loss%20of%20brain-specific%20RBFOX2-dependent%20splicing","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Loss of brain-specific RBFOX2-dependent splicing","description":"Two literatures meet at this node and they do not say the same thing, so the entry states both rather than picking the tidier one.\nIn non-neural cells, ZMYND11 couples the chromatin mark it reads directly to pre-mRNA processing: it associates with U5 snRNP spliceosome components and promotes intron retention by physically antagonising EFTUD2, and that regulation depends on its binding to H3K36me3-decorated chromatin. That is a direct, chromatin-dependent splicing role.\nIn human cortical cells it appears not to work that way. The corticogenesis study found that ZMYND11 did not largely regulate splicing directly - few differentially spliced events overlapped its chromatin binding - and attributes the splicing phenotype instead to increased RBFOX2 expression in the mutant, making the effect indirect. The disease-relevant output is a brain-specific RNA isoform switch, and it is partially rescuable by enhancing ZMYND11 function.\nThe incoming edge is graded INDIRECT_KNOWN_INTERMEDIATES to follow the cortical evidence, since that is the tissue this disease is about.","url":"https://dismech.monarchinitiative.org/pages/disorders/Intellectual_Disability,_Autosomal_Dominant_30.html#pathophysiology-loss-of-brain-specific-rbfox2-dependent-splicing","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3AIntellectual_Disability_Autosomal_Dominant_30:phenotype:Seizure","kind":"phenotype","kind_label":"Phenotype","label":"Seizure","description":"Epilepsy in ZMYND11 disorder is heterogeneous rather than a single syndrome. Among 20 individuals it split into atypical benign partial or idiopathic focal epilepsy, generalised epilepsies and infantile epileptic encephalopathy, and an unclassified group; prognosis ranged from spontaneous remission to drug resistance.","url":"https://dismech.monarchinitiative.org/pages/disorders/Intellectual_Disability,_Autosomal_Dominant_30.html#phenotype-seizure","resolved":true,"resolution_status":"resolved","candidate_kinds":["phenotype"],"distance":1,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Intellectual_Disability_Autosomal_Dominant_30.yaml:ZMYND11-deficient human embryonic stem cell-derived cortical neural stem cells","source_id":"model:kb/disorders/Intellectual_Disability_Autosomal_Dominant_30.yaml:ZMYND11-deficient human embryonic stem cell-derived cortical neural stem cells","target_id":"node:disorder%3AIntellectual_Disability_Autosomal_Dominant_30:pathophysiology:Impaired%20cortical%20progenitor%20and%20neuron%20production","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Partially Recapitulates","directed":false,"relationship":"PARTIALLY_RECAPITULATES","fidelity":"UNKNOWN","causal_link_type":null,"causal_link_type_label":null,"description":"ZMYND11-deficient cortical cultures produce fewer TBR2-positive intermediate progenitors and fewer TBR1-positive deep-layer neurons, and re-expressing ZMYND11 restores neuron differentiation in the cells that keep expressing the transgene. The heterozygous patient-like lines behave like the knockout, which is what makes the model relevant to a dominant disorder.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":4},{"id":"causal:disorder%3AIntellectual_Disability_Autosomal_Dominant_30:1:0","source_id":"node:disorder%3AIntellectual_Disability_Autosomal_Dominant_30:pathophysiology:De-repression%20of%20latent%20developmental%20transcriptional%20programmes","target_id":"node:disorder%3AIntellectual_Disability_Autosomal_Dominant_30:pathophysiology:Impaired%20cortical%20progenitor%20and%20neuron%20production","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[1].downstream[0]","label":"Directly causes","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"DIRECT","causal_link_type_label":"Direct","description":"De-repressed developmental programmes impair the production of cortical progenitors and 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disorder.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1},{"id":"causal:disorder%3AIntellectual_Disability_Autosomal_Dominant_30:3:1","source_id":"node:disorder%3AIntellectual_Disability_Autosomal_Dominant_30:pathophysiology:Impaired%20cortical%20progenitor%20and%20neuron%20production","target_id":"node:disorder%3AIntellectual_Disability_Autosomal_Dominant_30:phenotype:Seizure","kind":"causal","predicate":"causes","source_slot":"pathophysiology.downstream","source_location":"pathophysiology[3].downstream[1]","label":"Indirectly causes (unknown intermediates)","directed":true,"relationship":null,"fidelity":null,"causal_link_type":"INDIRECT_UNKNOWN_INTERMEDIATES","causal_link_type_label":"Indirect Unknown Intermediates","description":"Epilepsy in this disorder is grouped with the other chromatin-reader epilepsies, which places the seizure phenotype downstream of the same corticogenesis defect rather than of a separate channel 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corticogenesis.","intermediate_mechanisms":[],"hypothesis_groups":[],"evidence_count":1}]}}],"mechanism_names":["Impaired cortical progenitor and neuron production"],"relationships":["Partially Recapitulates"],"fidelities":["Unknown"],"biological_scales":["Tissue"],"system_context_sources":["Model-level cell type","Linked mechanism cell type","Linked mechanism biological scale"],"modeled_system_labels":["neural stem cell","neuron","Tissue"],"biological_process_terms":[{"id":"GO:0021987","label":"cerebral cortex development","display_label":"cerebral cortex development","url":"http://purl.obolibrary.org/obo/GO_0021987"}],"biological_processes":["cerebral cortex development"],"pathway_terms":[],"pathways":[],"gene_terms":[],"genes":[],"chemical_terms":[],"chemicals":[],"readout_names":["TBR2-positive intermediate progenitor generation","TBR1-positive deep-layer neuron generation","Neuron differentiation after ZMYND11 re-expression"],"readout_phenotype_terms":[],"readout_phenotypes":[],"readout_biomarker_terms":[],"readout_biomarkers":[],"readout_assay_terms":[],"readout_assays":[],"findings":[],"findings_text":[],"evidence":[{"reference":"PMID:41068108","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41068108","reference_title":"ZMYND11 functions in bimodal regulation of latent genes and brain-like splicing to safeguard corticogenesis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"we engineered loss-of-function and heterozygous/patient-like mutations in human embryonic stem cells (hESCs) to investigate its function in disease-relevant cell types within an isogenic background","explanation":"Describes how the model was built: isogenic knockout and heterozygous patient-like ZMYND11 lines in human embryonic stem cells."},{"reference":"PMID:41068108","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41068108","reference_title":"ZMYND11 functions in bimodal regulation of latent genes and brain-like splicing to safeguard corticogenesis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Here, we show that mutations in ZMYND11, a newly implicated risk gene, impair human cortical progenitor and neuron production.","explanation":"The study's own statement that the model shows the deficit this node describes."},{"reference":"PMID:41068108","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41068108","reference_title":"ZMYND11 functions in bimodal regulation of latent genes and brain-like splicing to safeguard corticogenesis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"No differences in IPC or neuron differentiation were observed between heterozygous and the knockout lines","explanation":"The heterozygous patient-like state reproduces the full deficit, so the model is informative for a haploinsufficient disorder and not only for complete loss."},{"reference":"PMID:41068108","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41068108","reference_title":"ZMYND11 functions in bimodal regulation of latent genes and brain-like splicing to safeguard corticogenesis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"To determine whether corticogenesis was delayed rather than permanently blocked, we analyzed a later time point (day 30) and observed a ~ 4-5-fold increase in IPCs","explanation":"The day-30 comparison shows the mutant cultures recover, the basis of the delay-not-block caveat in limitations."},{"reference":"PMID:41068108","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41068108","reference_title":"ZMYND11 functions in bimodal regulation of latent genes and brain-like splicing to safeguard corticogenesis.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"patients with ZMYND11 mutations did not display major brain malformations","explanation":"The authors' own statement of the human-model gap recorded in limitations. It restates earlier clinical reports rather than a result of this study."},{"reference":"PMID:41068108","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41068108","reference_title":"ZMYND11 functions in bimodal regulation of latent genes and brain-like splicing to safeguard corticogenesis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"we observed a ~ 4-7-fold decrease in IPC generation in ZMYND11 mutants","explanation":"Reports the measured fall in intermediate progenitor generation."},{"reference":"PMID:41068108","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41068108","reference_title":"ZMYND11 functions in bimodal regulation of latent genes and brain-like splicing to safeguard corticogenesis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"we found that the generation of TBR1-positive deep-layer neurons was also impaired to a similar magnitude","explanation":"Reports the measured fall in deep-layer neuron generation."},{"reference":"PMID:41068108","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41068108","reference_title":"ZMYND11 functions in bimodal regulation of latent genes and brain-like splicing to safeguard corticogenesis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"we specifically analyzed FLAG positive cells and found that neuron differentiation exhibited a ~ 4-fold increase, similar to the magnitude of decrease in ZMYND11 knockout","explanation":"Re-expression reverses the deficit by about the same magnitude as the loss, which ties the phenotype to ZMYND11 itself."}],"evidence_text":["we engineered loss-of-function and heterozygous/patient-like mutations in human embryonic stem cells (hESCs) to investigate its function in disease-relevant cell types within an isogenic background","Here, we show that mutations in ZMYND11, a newly implicated risk gene, impair human cortical progenitor and neuron production.","No differences in IPC or neuron differentiation were observed between heterozygous and the knockout lines","To determine whether corticogenesis was delayed rather than permanently blocked, we analyzed a later time point (day 30) and observed a ~ 4-5-fold increase in IPCs","patients with ZMYND11 mutations did not display major brain malformations","we observed a ~ 4-7-fold decrease in IPC generation in ZMYND11 mutants","we found that the generation of TBR1-positive deep-layer neurons was also impaired to a similar magnitude","we specifically analyzed FLAG positive cells and found that neuron differentiation exhibited a ~ 4-fold increase, similar to the magnitude of decrease in ZMYND11 knockout","Describes how the model was built: isogenic knockout and heterozygous patient-like ZMYND11 lines in human embryonic stem cells.","The study's own statement that the model shows the deficit this node describes.","The heterozygous patient-like state reproduces the full deficit, so the model is informative for a haploinsufficient disorder and not only for complete loss.","The day-30 comparison shows the mutant cultures recover, the basis of the delay-not-block caveat in limitations.","The authors' own statement of the human-model gap recorded in limitations. It restates earlier clinical reports rather than a result of this study.","Reports the measured fall in intermediate progenitor generation.","Reports the measured fall in deep-layer neuron generation.","Re-expression reverses the deficit by about the same magnitude as the loss, which ties the phenotype to ZMYND11 itself."],"evidence_status":"Evidence recorded","metadata_completeness":80,"metadata_present":["Model category","Organism","Cell type","Cell source","Culture system","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Anatomy"],"dataset_context":"None recorded in same entry","context_dataset_ids":[],"candidate_dataset_ids":[],"source_path":"kb/disorders/Intellectual_Disability_Autosomal_Dominant_30.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Intellectual_Disability_Autosomal_Dominant_30.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Intellectual_Disability,_Autosomal_Dominant_30.html#experimental-model-zmynd11-deficient-human-embryonic-stem-cell-derived-cortical-neural-stem-cells","source_anchor":"experimental-model-zmynd11-deficient-human-embryonic-stem-cell-derived-cortical-neural-stem-cells"},{"id":"model:kb/disorders/Pericarditis.yaml:Zymosan A intrapericardial injection mouse model","name":"Zymosan A intrapericardial injection mouse model","description":"Intrapericardial injection of zymosan A, producing pericardial inflammation with inflammasome activation matching that seen in human pericardial tissue. It was used to test inflammasome blockers against colchicine, and it is the source of the observation that colchicine improves pericardial inflammation only partially where interleukin-1 directed agents improve it substantially.\n","notes":null,"context_id":"disorder:Pericarditis","context_kind":"Disorder","disease_name":"Pericarditis","disease_synonyms":[],"disease_term":{"id":"MONDO:0005904","label":"pericarditis","display_label":"pericarditis","url":"http://purl.obolibrary.org/obo/MONDO_0005904"},"experimental_model_type":"OTHER","experimental_model_type_label":"Other","namo_type":null,"declared_namo_class_name":null,"namo_class_name":null,"namo_class_label":null,"namo_description":null,"namo_docs_url":null,"namo_ontology_url":null,"namo_mapping_basis":"Not mapped","namo_class_in_schema":false,"namo_schema_status":null,"modality":null,"organism":{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"house mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"},"organism_label":"Mus musculus","model_tissue":[],"model_tissue_labels":[],"linked_anatomy":[{"id":"UBERON:0002407","label":"pericardium","display_label":"pericardium","url":"http://purl.obolibrary.org/obo/UBERON_0002407"}],"linked_anatomy_labels":["pericardium"],"anatomy":[{"id":"UBERON:0002407","label":"pericardium","display_label":"pericardium","url":"http://purl.obolibrary.org/obo/UBERON_0002407"}],"anatomy_labels":["pericardium"],"tissue_label":null,"model_cell_types":[],"model_cell_type_labels":[],"linked_cell_types":[{"id":"CL:0000077","label":"mesothelial cell","display_label":"pericardial mesothelial cell","url":"http://purl.obolibrary.org/obo/CL_0000077"},{"id":"CL:0000235","label":"macrophage","display_label":"macrophage","url":"http://purl.obolibrary.org/obo/CL_0000235"}],"linked_cell_type_labels":["mesothelial cell","macrophage"],"cell_types":[{"id":"CL:0000077","label":"mesothelial cell","display_label":"pericardial mesothelial cell","url":"http://purl.obolibrary.org/obo/CL_0000077"},{"id":"CL:0000235","label":"macrophage","display_label":"macrophage","url":"http://purl.obolibrary.org/obo/CL_0000235"}],"cell_type_labels":["mesothelial cell","macrophage"],"conditions":[],"cell_source":null,"source_category":null,"culture_system":null,"publication":"PMID:33665514","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/33665514","mechanisms":[{"target":"Inflammasome activation in pericardial tissue","target_url":"https://dismech.monarchinitiative.org/pages/disorders/Pericarditis.html#pathophysiology-inflammasome-activation-in-pericardial-tissue","relationship":"NOT_SPECIFIED","relationship_label":"Not Specified","fidelity":"NOT_SPECIFIED","fidelity_label":"Not Specified","description":"The model reproduces inflammasome activation in the pericardium and allows blockers to be compared against each other.\n","limitations":null,"biological_scale":"CELLULAR","anatomy":[{"id":"UBERON:0002407","label":"pericardium","display_label":"pericardium","url":"http://purl.obolibrary.org/obo/UBERON_0002407"}],"cell_types":[{"id":"CL:0000077","label":"mesothelial cell","display_label":"pericardial mesothelial cell","url":"http://purl.obolibrary.org/obo/CL_0000077"},{"id":"CL:0000235","label":"macrophage","display_label":"macrophage","url":"http://purl.obolibrary.org/obo/CL_0000235"}],"biological_processes":[{"id":"GO:0044546","label":"NLRP3 inflammasome complex assembly","display_label":"NLRP3 inflammasome complex assembly","url":"http://purl.obolibrary.org/obo/GO_0044546"}],"pathways":[],"genes":[],"chemicals":[],"readouts":[],"evidence":[],"neighborhood":{"version":1,"scope":"one_hop_incident_causal_edges","status":"resolved","context_id":"disorder:Pericarditis","model_node_id":"model:kb/disorders/Pericarditis.yaml:Zymosan A intrapericardial injection mouse model","focus_node_id":"node:disorder%3APericarditis:pathophysiology:Inflammasome%20activation%20in%20pericardial%20tissue","source_pathograph_url":"https://dismech.monarchinitiative.org/pages/disorders/Pericarditis.html#pathograph","nodes":[{"id":"model:kb/disorders/Pericarditis.yaml:Zymosan A intrapericardial injection mouse model","kind":"experimental_model","kind_label":"NAM model","label":"Zymosan A intrapericardial injection mouse model","description":"Intrapericardial injection of zymosan A, producing pericardial inflammation with inflammasome activation matching that seen in human pericardial tissue. It was used to test inflammasome blockers against colchicine, and it is the source of the observation that colchicine improves pericardial inflammation only partially where interleukin-1 directed agents improve it substantially.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Pericarditis.html#experimental-model-zymosan-a-intrapericardial-injection-mouse-model","resolved":true,"resolution_status":"resolved","candidate_kinds":["experimental_model"],"distance":null,"biological_scale":null,"biological_scale_label":null,"mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APericarditis:pathophysiology:Inflammasome%20activation%20in%20pericardial%20tissue","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Inflammasome activation in pericardial tissue","description":"Innate immune sensing assembles the NLRP3 inflammasome in pericardial mesothelial cells and macrophages. This is the convergence point of the module, and it is established in human pericardial tissue rather than inferred from the drug response alone, with inflammasome components more strongly stained in patients with chronic pericarditis than in controls and the same activation reproduced in a mouse model of the disease.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Pericarditis.html#pathophysiology-inflammasome-activation-in-pericardial-tissue","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":0,"biological_scale":"CELLULAR","biological_scale_label":"Cellular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APericarditis:pathophysiology:Interleukin-1%20release%20and%20cytokine%20amplification","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Interleukin-1 release and cytokine amplification","description":"Active interleukin-1 alpha and beta drive a nuclear-factor-kappa-B-dependent cascade of interleukin-6, tumour necrosis factor, and chemokines. Interleukin-1 also induces its own production, which is the property that turns an injury response into a self-sustaining loop and gives the disease its tendency to recur. This node is the drug target for the two agents that work in refractory disease.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Pericarditis.html#pathophysiology-interleukin-1-release-and-cytokine-amplification","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"MOLECULAR","biological_scale_label":"Molecular","mechanism_confidence":null,"mechanism_confidence_label":null},{"id":"node:disorder%3APericarditis:pathophysiology:Pericardial%20injury%20from%20a%20heterogeneous%20trigger","kind":"pathophysiology","kind_label":"Pathophysiology event","label":"Pericardial injury from a heterogeneous trigger","description":"Viral infection, mycobacterial or pyogenic infection, uraemic toxin accumulation, myocardial or surgical injury, irradiation, malignant infiltration, or systemic autoimmune disease injures the pericardial mesothelium. The list is long and the downstream response is not, which is the central structural feature of this disease. Trigger identity determines the probability of progression to constriction and determines what treats the cause, but it barely determines the acute syndrome. Curating one trigger node rather than a separate chain per aetiology reflects that convergence.\n","url":"https://dismech.monarchinitiative.org/pages/disorders/Pericarditis.html#pathophysiology-pericardial-injury-from-a-heterogeneous-trigger","resolved":true,"resolution_status":"resolved","candidate_kinds":["pathophysiology"],"distance":1,"biological_scale":"TISSUE","biological_scale_label":"Tissue","mechanism_confidence":null,"mechanism_confidence_label":null}],"edges":[{"id":"model-link:0:model:kb/disorders/Pericarditis.yaml:Zymosan A intrapericardial injection mouse model","source_id":"model:kb/disorders/Pericarditis.yaml:Zymosan A intrapericardial injection mouse model","target_id":"node:disorder%3APericarditis:pathophysiology:Inflammasome%20activation%20in%20pericardial%20tissue","kind":"model_mechanism","predicate":null,"source_slot":"experimental_models.modeled_mechanisms","source_location":"modeled_mechanisms[0]","label":"Not 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inflammasome inhibitor, anakinra, and interleukin-1 trap were found to significantly improve pericardial alterations.","Describes the model and its route of induction.","Provides the preclinical counterpart of the two clinical trials curated on the treatment entries, testing the same pathway from the opposite direction."],"evidence_status":"Evidence recorded","metadata_completeness":70,"metadata_present":["Model category","Organism","Anatomy","Cell type","Modeled mechanism","Publication","Evidence"],"metadata_missing":["NAMO class","Cell source","Culture system"],"dataset_context":"None recorded in same 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The repository lists three disease groups and no linked publication at time of curation; sample count is the repository's own figure. ArrayExpress records are resolved against the BioStudies API on each verifier run and are not cached, so this record carries no quoted evidence."],"contexts":[{"id":"disorder:Rosacea","name":"Rosacea","kind":"Disorder","source_path":"kb/disorders/Rosacea.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rosacea.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Rosacea.html#dataset-arrayexpress-e-mtab-16629"}],"context_names":["Rosacea"],"disease_names":["Rosacea"],"disease_name":"Rosacea","same_context_model_ids":["model:kb/disorders/Rosacea.yaml:HaCaT keratinocytes under simulated rosacea conditions","model:kb/disorders/Rosacea.yaml:Paired lesional and non-lesional papulopustular rosacea skin explants","model:kb/disorders/Rosacea.yaml:SZ95 sebocyte and live Demodex mite co-culture"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Rosacea.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rosacea.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Rosacea.html#dataset-arrayexpress-e-mtab-16629"]},{"id":"dataset:bioproject:prjdb18292","accession":"bioproject:PRJDB18292","repository":"Bioproject","accession_url":"https://www.ncbi.nlm.nih.gov/bioproject/PRJDB18292","title":"Topical ivermectin treatment of rosacea changes the bacterial microbiome of the skin","alternate_titles":[],"description":"16S bacterial microbiome of facial skin in rosacea patients sampled before and after topical ivermectin treatment (24 SRA experiments, DDBJ). 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The project registration (2020-06-26) and description match Woo et al. 2020, Br J Dermatol, PMID:32533846 (\"Bacterial and fungal microbiome characterization in patients with rosacea and healthy controls\"), but the repository lists no publication link, so the PMID is recorded here rather than in publication. No data_type is set because the schema enum has no value for amplicon (16S/ITS) metagenomics."],"contexts":[{"id":"disorder:Rosacea","name":"Rosacea","kind":"Disorder","source_path":"kb/disorders/Rosacea.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rosacea.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Rosacea.html#dataset-bioproject-prjeb37562"}],"context_names":["Rosacea"],"disease_names":["Rosacea"],"disease_name":"Rosacea","same_context_model_ids":["model:kb/disorders/Rosacea.yaml:HaCaT keratinocytes under simulated rosacea conditions","model:kb/disorders/Rosacea.yaml:Paired lesional and non-lesional papulopustular rosacea skin explants","model:kb/disorders/Rosacea.yaml:SZ95 sebocyte and live Demodex mite co-culture"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Rosacea.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rosacea.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Rosacea.html#dataset-bioproject-prjeb37562"]},{"id":"dataset:bioproject:prjeb82826","accession":"bioproject:PRJEB82826","repository":"Bioproject","accession_url":"https://www.ncbi.nlm.nih.gov/bioproject/PRJEB82826","title":"Multi-omics study of microbe-host interactions in rosacea","alternate_titles":[],"description":"Cutaneous microbiome (96 amplicon runs in ENA) with paired Demodex density and host skin transcriptome from rosacea patients before and after 30 days of topical 1% ivermectin, versus healthy volunteers. The dataset that separates the mite, microbiome and host-transcriptome arms of the Demodex mechanism: ivermectin cleared mites and normalized the host transcriptome without correcting bacterial dysbiosis.","alternate_descriptions":[],"data_types":["MULTI_OMICS"],"data_type_labels":["Multi Omics"],"data_type_label":"Multi Omics","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:1000021","label":"skin of face","display_label":"skin of face","url":"http://purl.obolibrary.org/obo/UBERON_1000021"}],"sample_type_labels":["skin of face"],"sample_counts":[96],"sample_count":96,"conditions":["rosacea lesional skin, day 0 (pre-ivermectin)","rosacea lesional skin, day 30 (post-ivermectin)","healthy volunteer skin"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40220854"],"publication_contexts":[{"context_id":"disorder:Rosacea","publication":"PMID:40220854"}],"publication":"PMID:40220854","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40220854","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:40220854","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40220854","reference_title":"Microbe-Host Interaction in Rosacea and Its Modulation through Topical Ivermectin.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"At day 0, distinct microbial community changes included the decrease in Cutibacterium acnes abundance, whereas Staphylococcus epidermidis colonization increased compared with that in healthy volunteers.","explanation":"The cutaneous dysbiosis signature measured in this dataset."},{"reference":"PMID:40220854","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40220854","reference_title":"Microbe-Host Interaction in Rosacea and Its Modulation through Topical Ivermectin.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"However, improvement of clinical signs during topical ivermectin is not associated with normalization of the bacterial microbiome but rather a decrease of transcriptomic dysregulation and mite density.","explanation":"Dissociates the treatment response from bacterial dysbiosis and ties it to mite clearance and host transcriptome normalization, the Demodex-directed reading of the acaricide link in this entry."}],"notes":["Sample count is the number of amplicon read runs in ENA; a sibling umbrella accession, PRJEB82848, carries the same title and description but no data objects and is not recorded separately. The host transcriptome arm is not among the ENA runs under this accession."],"contexts":[{"id":"disorder:Rosacea","name":"Rosacea","kind":"Disorder","source_path":"kb/disorders/Rosacea.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rosacea.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Rosacea.html#dataset-bioproject-prjeb82826"}],"context_names":["Rosacea"],"disease_names":["Rosacea"],"disease_name":"Rosacea","same_context_model_ids":["model:kb/disorders/Rosacea.yaml:HaCaT keratinocytes under simulated rosacea conditions","model:kb/disorders/Rosacea.yaml:Paired lesional and non-lesional papulopustular rosacea skin explants","model:kb/disorders/Rosacea.yaml:SZ95 sebocyte and live Demodex mite co-culture"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a 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No linked publication on the record at time of curation; no data_type is set because the schema enum has no value for amplicon (16S) metagenomics."],"contexts":[{"id":"disorder:Rosacea","name":"Rosacea","kind":"Disorder","source_path":"kb/disorders/Rosacea.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rosacea.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Rosacea.html#dataset-bioproject-prjna1189573"}],"context_names":["Rosacea"],"disease_names":["Rosacea"],"disease_name":"Rosacea","same_context_model_ids":["model:kb/disorders/Rosacea.yaml:HaCaT keratinocytes under simulated rosacea conditions","model:kb/disorders/Rosacea.yaml:Paired lesional and non-lesional papulopustular rosacea skin explants","model:kb/disorders/Rosacea.yaml:SZ95 sebocyte and live Demodex mite co-culture"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Rosacea.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rosacea.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Rosacea.html#dataset-bioproject-prjna1189573"]},{"id":"dataset:bioproject:prjna1191396","accession":"bioproject:PRJNA1191396","repository":"Bioproject","accession_url":"https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1191396","title":"Raw 16S rRNA Sequencing Data of Fecal Samples from Patients with Neurogenic Rosacea","alternate_titles":[],"description":"Fecal 16S rRNA microbiome from patients with neurogenic rosacea (34 SRA experiments), the burning/stinging-predominant presentation, probing the gut-skin-nerve axis behind the TRP and neuropeptide signaling node.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0001988","label":"feces","display_label":"feces","url":"http://purl.obolibrary.org/obo/UBERON_0001988"}],"sample_type_labels":["feces"],"sample_counts":[34],"sample_count":34,"conditions":["neurogenic rosacea fecal samples"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Sample count is the number of SRA experiments. The record does not say whether controls are included. No linked publication on the record at time of curation; no data_type is set because the schema enum has no value for amplicon (16S) metagenomics."],"contexts":[{"id":"disorder:Rosacea","name":"Rosacea","kind":"Disorder","source_path":"kb/disorders/Rosacea.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rosacea.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Rosacea.html#dataset-bioproject-prjna1191396"}],"context_names":["Rosacea"],"disease_names":["Rosacea"],"disease_name":"Rosacea","same_context_model_ids":["model:kb/disorders/Rosacea.yaml:HaCaT keratinocytes under simulated rosacea conditions","model:kb/disorders/Rosacea.yaml:Paired lesional and non-lesional papulopustular rosacea skin explants","model:kb/disorders/Rosacea.yaml:SZ95 sebocyte and live Demodex mite co-culture"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Rosacea.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rosacea.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Rosacea.html#dataset-bioproject-prjna1191396"]},{"id":"dataset:bioproject:prjna1257465","accession":"bioproject:PRJNA1257465","repository":"Bioproject","accession_url":"https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1257465","title":"Auto-brewery syndrome flare, remission, household-partner, and FMT microbiome sequencing","alternate_titles":[],"description":"Public shotgun metagenomic and ITS2 sequencing from the 2026 observational cohort, including ABS flare and remission samples, unaffected household partners, and longitudinal samples around FMT. 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study.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"The annual increase of the SARA score was greatest in SCA1 (2.18 ± 0.17, mean ± SE) followed by SCA3 (1.61 ± 0.12) and SCA2 (1.40 ± 0.11).","explanation":"Provides a published cohort finding from the EUROSCA dataset."}],"notes":[],"contexts":[{"id":"disorder:Autosomal_Dominant_Cerebellar_Ataxia_Type_I","name":"Autosomal Dominant Cerebellar Ataxia Type I","kind":"Disorder","source_path":"kb/disorders/Autosomal_Dominant_Cerebellar_Ataxia_Type_I.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autosomal_Dominant_Cerebellar_Ataxia_Type_I.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Dominant_Cerebellar_Ataxia_Type_I.html#dataset-clinicaltrials-nct02440763"}],"context_names":["Autosomal Dominant Cerebellar Ataxia Type I"],"disease_names":["Autosomal Dominant Cerebellar Ataxia Type 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caries (also known as tooth decay) remains the most common chronic disease of childhood, five times more common than asthma and seven times more common than environmental allergies, with more than 40% of children exhibiting caries when they enter kindergarten. In 2005, it was estimated that dental health care costs were approximately $84 billion, of which 60% or about $50 billion were related to treatment of dental caries.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Dental Caries\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Dental_Caries","name":"Dental Caries","kind":"Disorder","source_path":"kb/disorders/Dental_Caries.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dental_Caries.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Dental_Caries.html#dataset-dbgap-phs000095"}],"context_names":["Dental Caries"],"disease_names":["Dental Caries"],"disease_name":"Dental Caries","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Dental_Caries.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dental_Caries.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Dental_Caries.html#dataset-dbgap-phs000095"]},{"id":"dataset:dbgap:phs000102","accession":"dbgap:phs000102","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000102","title":"Ischemic Stroke Genetics Study (ISGS)","alternate_titles":[],"description":"The third leading cause of death in the United States, stroke is an acute neurological event leading to death of neural tissues. Although the majority of strokes are ischemic strokes, meaning there is oxygen deprivation to the brain, almost 20% of strokes are hemorrhagic, resulting from bleeding into the brain. Stroke is a complex disorder and likely multigenic in nature, resulting from a combination of genetic and environmental factors.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Ischemic Stroke\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Ischemic_Stroke","name":"Ischemic Stroke","kind":"Disorder","source_path":"kb/disorders/Ischemic_Stroke.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ischemic_Stroke.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Ischemic_Stroke.html#dataset-dbgap-phs000102"}],"context_names":["Ischemic Stroke"],"disease_names":["Ischemic Stroke"],"disease_name":"Ischemic Stroke","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Ischemic_Stroke.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ischemic_Stroke.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Ischemic_Stroke.html#dataset-dbgap-phs000102"]},{"id":"dataset:dbgap:phs000222","accession":"dbgap:phs000222","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000222","title":"PREDICT-HD Huntington Disease Study","alternate_titles":[],"description":"The purpose of this project is to make clinical measurements from the PREDICT-HD consortium available through the dbGaP mechanism. The phenotype data will first be converted into a community open standard and subsequently exported to dbGaP for archival and open access distribution of the results of the studies. This will permit members of the scientific community to utilize a permanent resource for investigating the interactions of phenotypes upon an international cohort of early Huntington Disease.   In  version 2  cut of the data we provided HD CAG repeat lengths for both allele","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Huntington Disease\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Huntington_Disease","name":"Huntington Disease","kind":"Disorder","source_path":"kb/disorders/Huntington_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Huntington_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Huntington_Disease.html#dataset-dbgap-phs000222"}],"context_names":["Huntington Disease"],"disease_names":["Huntington Disease"],"disease_name":"Huntington Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Huntington_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Huntington_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Huntington_Disease.html#dataset-dbgap-phs000222"]},{"id":"dataset:dbgap:phs000274","accession":"dbgap:phs000274","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000274","title":"Genome-Wide Association Study of Celiac Disease","alternate_titles":[],"description":"Celiac disease (gluten-sensitive enteropathy, celiac sprue) is a common disease with significant morbidity and mortality. It is caused by sensitivity to the dietary protein gluten, resulting in a chronic enteropathy in the small intestine. Celiac disease is now recognized to be a common disease, with reports that the disease frequency is 1:133 in the United States, similar to European estimates. There is recent evidence to suggest that the incidence of the disease is rising. Occult disease is frequently present with minimal classic symptoms or signs.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Celiac Disease\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Celiac_Disease","name":"Celiac Disease","kind":"Disorder","source_path":"kb/disorders/Celiac_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Celiac_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Celiac_Disease.html#dataset-dbgap-phs000274"}],"context_names":["Celiac Disease"],"disease_names":["Celiac Disease"],"disease_name":"Celiac Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Celiac_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Celiac_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Celiac_Disease.html#dataset-dbgap-phs000274"]},{"id":"dataset:dbgap:phs000352","accession":"dbgap:phs000352","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000352","title":"Sequencing of Retinoblastoma","alternate_titles":[],"description":"Retinoblastoma is a pediatric cancer of the developing retina. All retinoblastomas are believed to initiate with biallelic inactivation of the RB1 gene. To identify subsequent genetic lesions in retinoblastoma, we performed whole genome sequencing of tumor and normal DNA of 4 children with retinoblastoma and one matched orthotopic xenograft. Both alleles of RB1 were inactivated in the tumor samples. 3 of the patients had sporadic retinoblastoma and one patient had inherited retinoblastoma.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Retinoblastoma\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Retinoblastoma","name":"Retinoblastoma","kind":"Disorder","source_path":"kb/disorders/Retinoblastoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Retinoblastoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Retinoblastoma.html#dataset-dbgap-phs000352"}],"context_names":["Retinoblastoma"],"disease_names":["Retinoblastoma"],"disease_name":"Retinoblastoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Retinoblastoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Retinoblastoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Retinoblastoma.html#dataset-dbgap-phs000352"]},{"id":"dataset:dbgap:phs000357","accession":"dbgap:phs000357","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000357","title":"Genome-Wide Association Study in Systemic Sclerosis","alternate_titles":[],"description":"The Scleroderma Family Registry and DNA Repository (Registry) was initially developed as a registry and bio-specimen repository of patients with systemic sclerosis (scleroderma), family members and unaffected healthy controls. A case-control design was later adopted due to the lack of availability of many parents in this adult-onset disease, which precluded a linkage approach. In addition to collecting demographic data, the registry included the collection of disease-pertinent, cross-sectional, clinical information from medical records of affected participants.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Systemic Sclerosis\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Systemic_Sclerosis","name":"Systemic Sclerosis","kind":"Disorder","source_path":"kb/disorders/Systemic_Sclerosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Systemic_Sclerosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Systemic_Sclerosis.html#dataset-dbgap-phs000357"}],"context_names":["Systemic Sclerosis"],"disease_names":["Systemic Sclerosis"],"disease_name":"Systemic Sclerosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Systemic_Sclerosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Systemic_Sclerosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Systemic_Sclerosis.html#dataset-dbgap-phs000357"]},{"id":"dataset:dbgap:phs000364","accession":"dbgap:phs000364","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000364","title":"Genome-Wide Analysis of Chronic Lymphocytic Leukemia","alternate_titles":[],"description":"Analysis of the chronic lymphocytic leukemia coding genome: role of NOTCH1 mutational activation    The pathogenesis of chronic lymphocytic leukemia (CLL), the most common leukemia in adults, is still largely unknown since the full spectrum of genetic lesions that are present in the CLL genome, and therefore the number and identity of dysregulated cellular pathways, have not been identified. By combining next-generation sequencing and copy number analysis, we show here that the typical CLL coding genome contains less than 20 clonally represented gene alterations/case, including p","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Chronic Lymphocytic Leukemia\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Chronic_Lymphocytic_Leukemia","name":"Chronic Lymphocytic Leukemia","kind":"Disorder","source_path":"kb/disorders/Chronic_Lymphocytic_Leukemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Lymphocytic_Leukemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chronic_Lymphocytic_Leukemia.html#dataset-dbgap-phs000364"}],"context_names":["Chronic Lymphocytic Leukemia"],"disease_names":["Chronic Lymphocytic Leukemia"],"disease_name":"Chronic Lymphocytic Leukemia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chronic_Lymphocytic_Leukemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Lymphocytic_Leukemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chronic_Lymphocytic_Leukemia.html#dataset-dbgap-phs000364"]},{"id":"dataset:dbgap:phs000387","accession":"dbgap:phs000387","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000387","title":"Geisinger eMERGE - Abdominal Aortic Aneurysm Project (AAAP)","alternate_titles":[],"description":"A large research cohort of Geisinger Abdominal Aortic Aneurysm (AAA) patients was created by enrolling and consenting patients of the Geisinger Department of Vascular Surgery. Consented patients provide blood, serum and DNA samples for research and authorize use of data in their medical record for research. They also complete a data questionnaire that asks information about family history of AAA and other vascular diseases, as well as information on known or suspected AAA risk factors, including smoking history, body mass index, hypertension, type 2 diabetes, and atherosclerotic disease.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Abdominal Aortic Aneurysm\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Abdominal_Aortic_Aneurysm","name":"Abdominal Aortic Aneurysm","kind":"Disorder","source_path":"kb/disorders/Abdominal_Aortic_Aneurysm.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Abdominal_Aortic_Aneurysm.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Abdominal_Aortic_Aneurysm.html#dataset-dbgap-phs000387"}],"context_names":["Abdominal Aortic Aneurysm"],"disease_names":["Abdominal Aortic Aneurysm"],"disease_name":"Abdominal Aortic Aneurysm","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Abdominal_Aortic_Aneurysm.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Abdominal_Aortic_Aneurysm.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Abdominal_Aortic_Aneurysm.html#dataset-dbgap-phs000387"]},{"id":"dataset:dbgap:phs000409","accession":"dbgap:phs000409","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000409","title":"Sequencing of Medulloblastoma","alternate_titles":[],"description":"Medulloblastoma is a heterogenous disease made up of at least four distinct subtypes of disease which appear to exploit and disrupt naturally occurring developmental pathways of cellular growth and hindbrain development. To better understand the driver mutations of this disease, we performed whole genome sequencing of 37 medulloblastomas and the corresponding normal DNA of the 37 affected children treated at St. Jude Children's Research Hospital. We have found several novel mutations which appear subtype specific.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Medulloblastoma\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Medulloblastoma","name":"Medulloblastoma","kind":"Disorder","source_path":"kb/disorders/Medulloblastoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Medulloblastoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Medulloblastoma.html#dataset-dbgap-phs000409"}],"context_names":["Medulloblastoma"],"disease_names":["Medulloblastoma"],"disease_name":"Medulloblastoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Medulloblastoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Medulloblastoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Medulloblastoma.html#dataset-dbgap-phs000409"]},{"id":"dataset:dbgap:phs000430","accession":"dbgap:phs000430","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000430","title":"Hepatitis C Antiviral Long-term Treatment Against Cirrhosis (HALT-C)","alternate_titles":[],"description":"Reprinted from http://www.haltctrial.org/    Purpose    The  H epatitis C  A ntiviral  L ong-term  T reatment against  C irrhosis (HALT-C) Trial is a randomized controlled trial designed to evaluate the safety and efficacy of long-term use of pegylated interferon for the treatment of chronic hepatitis C in patients who failed to respond to previous interferon therapy. The HALT-C Trial was developed to determine whether prolonged interferon therapy altered histological and clinical outcomes in a group of patients who had failed to eradicate hepatitis C","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Hepatitis C\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Hepatitis_C","name":"Hepatitis C","kind":"Disorder","source_path":"kb/disorders/Hepatitis_C.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatitis_C.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hepatitis_C.html#dataset-dbgap-phs000430"}],"context_names":["Hepatitis C"],"disease_names":["Hepatitis C"],"disease_name":"Hepatitis C","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hepatitis_C.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatitis_C.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hepatitis_C.html#dataset-dbgap-phs000430"]},{"id":"dataset:dbgap:phs000431","accession":"dbgap:phs000431","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000431","title":"IgA Nephropathy GWAS (IGANGWAS)","alternate_titles":[],"description":"In this second study version, we report a genome-wide association study of IgA nephropathy performed in individuals of European ancestry (US and Italian cohorts), followed by a meta-analysis with the existing GWAS cohorts (Han Chinese [study version 1] and French cohorts). Genomic DNA was extracted from whole blood and genotyped with the HumanHap550-2v3, Human610-Quadv1and HumanOmni1-Quad_v1 platforms. This GWAS also utilized pre-genotyped population controls from other studies.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"IgA Nephropathy\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:IgA_Nephropathy","name":"IgA Nephropathy","kind":"Disorder","source_path":"kb/disorders/IgA_Nephropathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/IgA_Nephropathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/IgA_Nephropathy.html#dataset-dbgap-phs000431"}],"context_names":["IgA Nephropathy"],"disease_names":["IgA Nephropathy"],"disease_name":"IgA Nephropathy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/IgA_Nephropathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/IgA_Nephropathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/IgA_Nephropathy.html#dataset-dbgap-phs000431"]},{"id":"dataset:dbgap:phs000437","accession":"dbgap:phs000437","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000437","title":"Next Generation Mendelian Genetics: Auriculocondylar Syndrome (ACS)","alternate_titles":[],"description":"This project is part of an ongoing project to identify the molecular genetic basis of rare craniofacial disorders. This specific project involved the collection of DNA samples from four probands with severe manifestations of auriculocondylar syndrome and their parents. Detailed clinical phenotypic data is available on each proband. The sole purpose of this research is to identify the molecular cause(s) of auriculochondylar syndrome.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["The dbGaP accession and disease-specific title were verified against the live repository on 2026-09-21. The project describes four severe ACS probands and their parents; it is a gene-discovery collection, not a representative phenotype-frequency cohort."],"contexts":[{"id":"disorder:Auriculocondylar_Syndrome","name":"Auriculocondylar Syndrome","kind":"Disorder","source_path":"kb/disorders/Auriculocondylar_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Auriculocondylar_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Auriculocondylar_Syndrome.html#dataset-dbgap-phs000437"}],"context_names":["Auriculocondylar Syndrome"],"disease_names":["Auriculocondylar Syndrome"],"disease_name":"Auriculocondylar Syndrome","same_context_model_ids":["model:kb/disorders/Auriculocondylar_Syndrome.yaml:ACS patient mandibular osteoblast cultures","model:kb/disorders/Auriculocondylar_Syndrome.yaml:GNAI3-variant signaling in HEK293T cells","model:kb/disorders/Auriculocondylar_Syndrome.yaml:PLCB4-variant DAG and transcriptional reporter assays","model:kb/disorders/Auriculocondylar_Syndrome.yaml:Purified GNAI3 S47R nucleotide-binding assays","model:kb/disorders/Auriculocondylar_Syndrome.yaml:Regulatory-duplication neural-crest mesenchymal derivatives","model:kb/disorders/Auriculocondylar_Syndrome.yaml:Regulatory-duplication patient iPSC neural-crest cultures"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Auriculocondylar_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Auriculocondylar_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Auriculocondylar_Syndrome.html#dataset-dbgap-phs000437"]},{"id":"dataset:dbgap:phs000440","accession":"dbgap:phs000440","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000440","title":"CCDG: Dental Caries and CL/P in Guatemala","alternate_titles":[],"description":"This study provides an opportunity to investigate the genetics of both dental caries and orofacial clefts (OFCs) in one set of families ascertained in Guatemala. This study is part of the Gene Environment Association Studies initiative (GENEVA, http://www.genevastudy.org), which was developed through the trans-NIH Genes, Environment, and Health Initiative (GEI).","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Dental Caries\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Dental_Caries","name":"Dental Caries","kind":"Disorder","source_path":"kb/disorders/Dental_Caries.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dental_Caries.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Dental_Caries.html#dataset-dbgap-phs000440"}],"context_names":["Dental Caries"],"disease_names":["Dental Caries"],"disease_name":"Dental Caries","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Dental_Caries.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dental_Caries.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Dental_Caries.html#dataset-dbgap-phs000440"]},{"id":"dataset:dbgap:phs000471","accession":"dbgap:phs000471","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000471","title":"TARGET: Kidney, Wilms Tumor (WT)","alternate_titles":[],"description":"TARGET high-risk Wilms tumor cohort with matched tumor-normal profiling, including gene expression, copy number, methylation, whole genome sequencing, and subset mRNA-seq, miRNA-seq, and whole exome sequencing.","alternate_descriptions":[],"data_types":["MULTI_OMICS"],"data_type_labels":["Multi Omics"],"data_type_label":"Multi Omics","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0002113","label":"kidney","display_label":"kidney","url":"http://purl.obolibrary.org/obo/UBERON_0002113"}],"sample_type_labels":["kidney"],"sample_counts":[130],"sample_count":130,"conditions":["high-risk Wilms tumor","anaplastic Wilms tumor","relapsed favorable histology Wilms tumor"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["dbGaP describes 130 fully characterized high-risk Wilms tumor cases with tumor-normal pairs, selected largely from anaplastic tumors or favorable histology tumors that relapsed."],"contexts":[{"id":"disorder:Wilms_Tumor","name":"Wilms Tumor","kind":"Disorder","source_path":"kb/disorders/Wilms_Tumor.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Wilms_Tumor.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Wilms_Tumor.html#dataset-dbgap-phs000471"}],"context_names":["Wilms Tumor"],"disease_names":["Wilms Tumor"],"disease_name":"Wilms Tumor","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Wilms_Tumor.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Wilms_Tumor.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Wilms_Tumor.html#dataset-dbgap-phs000471"]},{"id":"dataset:dbgap:phs000476","accession":"dbgap:phs000476","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000476","title":"Molecular Defects in Pseudohypoparathyroidism or Related Disorders","alternate_titles":[],"description":"Maintaining calcium levels within a narrow normal range is of critical importance for numerous different cellular functions. One of the most important regulators of blood calcium levels is parathyroid hormone (PTH), which mediates its actions through the PTH/PTHrP receptor, a Gαs-coupled receptor.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Pseudohypoparathyroidism\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Pseudohypoparathyroidism","name":"Pseudohypoparathyroidism","kind":"Disorder","source_path":"kb/disorders/Pseudohypoparathyroidism.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pseudohypoparathyroidism.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pseudohypoparathyroidism.html#dataset-dbgap-phs000476"}],"context_names":["Pseudohypoparathyroidism"],"disease_names":["Pseudohypoparathyroidism"],"disease_name":"Pseudohypoparathyroidism","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Pseudohypoparathyroidism.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pseudohypoparathyroidism.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Pseudohypoparathyroidism.html#dataset-dbgap-phs000476"]},{"id":"dataset:dbgap:phs000497","accession":"dbgap:phs000497","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000497","title":"Genetic Analysis of Hirschsprung Disease","alternate_titles":[],"description":"Hirschsprung disease (HSCR) is a birth defect resulting from the absence of nerve (ganglion) cells in the gastrointestinal tract. Hirschsprung disease has a population incidence of 1/5,000 live births and most often occurs as an isolated condition. However, approximately 30% of HSCR cases are associated with other birth defects such as Down syndrome, deafness, hypopigmentation, and Congenital Central Hypoventilation syndrome (CCHS). Hirschsprung disease is a genetic condition with autosomal dominant, autosomal recessive, and multigenic patterns of inheritance described.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Hirschsprung Disease\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Hirschsprung_Disease","name":"Hirschsprung Disease","kind":"Disorder","source_path":"kb/disorders/Hirschsprung_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hirschsprung_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hirschsprung_Disease.html#dataset-dbgap-phs000497"}],"context_names":["Hirschsprung Disease"],"disease_names":["Hirschsprung Disease"],"disease_name":"Hirschsprung Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hirschsprung_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hirschsprung_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hirschsprung_Disease.html#dataset-dbgap-phs000497"]},{"id":"dataset:dbgap:phs000502","accession":"dbgap:phs000502","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000502","title":"Genome-Wide Analysis of Splenic Marginal Zone Lymphoma","alternate_titles":[],"description":"Splenic Marginal Zone Lymphoma (SMZL) is a B-cell malignancy of unknown pathogenesis and thus orphan of targeted therapies. By integrating whole-exome sequencing and copy-number analysis of 8 paired tumor-normal DNAs from patients with SMZL, we show that the typical SMZL exome carries ~30 genetic alterations. Targeted resequencing of selected candidates in an extended panel of 40-117 samples revealed activating mutations of NOTCH2, a gene required for marginal-zone (MZ) development, as the most frequent and SMZL-specific lesion, accounting for approximately 20% of cases.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Splenic Marginal Zone Lymphoma\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Splenic_Marginal_Zone_Lymphoma","name":"Splenic Marginal Zone Lymphoma","kind":"Disorder","source_path":"kb/disorders/Splenic_Marginal_Zone_Lymphoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Splenic_Marginal_Zone_Lymphoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Splenic_Marginal_Zone_Lymphoma.html#dataset-dbgap-phs000502"}],"context_names":["Splenic Marginal Zone Lymphoma"],"disease_names":["Splenic Marginal Zone Lymphoma"],"disease_name":"Splenic Marginal Zone Lymphoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Splenic_Marginal_Zone_Lymphoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Splenic_Marginal_Zone_Lymphoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Splenic_Marginal_Zone_Lymphoma.html#dataset-dbgap-phs000502"]},{"id":"dataset:dbgap:phs000518","accession":"dbgap:phs000518","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000518","title":"NHLBI GO-ESP Family Studies: Idiopathic Bronchiectasis","alternate_titles":[],"description":"The NHLBI \"Grand Opportunity\" Exome Sequencing Project (GO-ESP), a signature project of the NHLBI Recovery Act investment, was designed to identify genetic variants in coding regions (exons) of the human genome (the \"exome\") that are associated with heart, lung and blood diseases. These and related diseases that are of high impact to public health and individuals from diverse racial and ethnic groups will be studied.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Bronchiectasis\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Bronchiectasis","name":"Bronchiectasis","kind":"Disorder","source_path":"kb/disorders/Bronchiectasis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bronchiectasis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Bronchiectasis.html#dataset-dbgap-phs000518"}],"context_names":["Bronchiectasis"],"disease_names":["Bronchiectasis"],"disease_name":"Bronchiectasis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Bronchiectasis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bronchiectasis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Bronchiectasis.html#dataset-dbgap-phs000518"]},{"id":"dataset:dbgap:phs000521","accession":"dbgap:phs000521","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000521","title":"Episodic Ataxia Syndrome","alternate_titles":[],"description":"Individuals with episodic ataxia experience recurrent attacks of dizziness and incoordination; between attacks patients are typically normal. The majority of cases are likely caused by an inherited genetic mutation. However, in some patients we are unable to identify the mutation. So far, 2 genes have been identified which cause different types of episodic ataxia. Ultimately, when the actual mutation is identified the protein product of the gene can be studied and specific medications can be designed.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Episodic Ataxia\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Episodic_Ataxia","name":"Episodic Ataxia","kind":"Disorder","source_path":"kb/disorders/Episodic_Ataxia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Episodic_Ataxia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Episodic_Ataxia.html#dataset-dbgap-phs000521"}],"context_names":["Episodic Ataxia"],"disease_names":["Episodic Ataxia"],"disease_name":"Episodic Ataxia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Episodic_Ataxia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Episodic_Ataxia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Episodic_Ataxia.html#dataset-dbgap-phs000521"]},{"id":"dataset:dbgap:phs000537","accession":"dbgap:phs000537","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000537","title":"Next Generation Mendelian Genetics: Familial Hemophagocytic Lymphohistiocytosis","alternate_titles":[],"description":"The NHGRI Next Generation Mendelian Genetics project uses exome resequencing to identify variants in unsolved Mendelian diseases. Familial hemophagocytic lymphohistiocytosis (fHLH) is a serious immune disorder that results from defective cytotoxic lymphocyte function. Autosomal recessive mutations in PFP1, UNC13D, STX11, STBP2, or RAB27, and hemizygous mutations in SH2D1A or BIRC4, account for known causes of the disease, but 30-70% of patients in North America lack a known genetic etiology. This project was designed to identify additional genetic abnormalities from HLH patients.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Hemophagocytic Lymphohistiocytosis\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Hemophagocytic_Lymphohistiocytosis","name":"Hemophagocytic Lymphohistiocytosis","kind":"Disorder","source_path":"kb/disorders/Hemophagocytic_Lymphohistiocytosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hemophagocytic_Lymphohistiocytosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hemophagocytic_Lymphohistiocytosis.html#dataset-dbgap-phs000537"}],"context_names":["Hemophagocytic Lymphohistiocytosis"],"disease_names":["Hemophagocytic Lymphohistiocytosis"],"disease_name":"Hemophagocytic Lymphohistiocytosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hemophagocytic_Lymphohistiocytosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hemophagocytic_Lymphohistiocytosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hemophagocytic_Lymphohistiocytosis.html#dataset-dbgap-phs000537"]},{"id":"dataset:dbgap:phs000540","accession":"dbgap:phs000540","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000540","title":"Next Generation Mendelian Genetics: Ehlers-Danlos Syndrome Type VIII","alternate_titles":[],"description":"The NHGRI Next Generation Mendelian Genetics project uses exome resequencing to identify variants in unsolved Mendelian diseases. Ehlers-Danlos syndrome Type VIII is a dominantly inherited connective tissue disorder that is distinguished from other forms of EDS by significant early-onset periodontal disease. Although the clinical phenotype is well delineated, the underlying molecular basis remains unknown.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Ehlers-Danlos Syndrome\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Ehlers-Danlos_Syndrome","name":"Ehlers-Danlos Syndrome","kind":"Disorder","source_path":"kb/disorders/Ehlers-Danlos_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ehlers-Danlos_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Ehlers-Danlos_Syndrome.html#dataset-dbgap-phs000540"}],"context_names":["Ehlers-Danlos Syndrome"],"disease_names":["Ehlers-Danlos Syndrome"],"disease_name":"Ehlers-Danlos Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Ehlers-Danlos_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ehlers-Danlos_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Ehlers-Danlos_Syndrome.html#dataset-dbgap-phs000540"]},{"id":"dataset:dbgap:phs000543","accession":"dbgap:phs000543","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000543","title":"Exome Sequencing of Pleuropulmonary Blastoma","alternate_titles":[],"description":"Pleuropulmonary blastoma (PPB) is a rare, aggressive pediatric cancer arising from the lung or pleural cavity. In this study, we sequenced and analyzed the exomes of 15 PPB matched tumor and normal pairs. This study is part of a larger effort to characterize pediatric cancers as part of the Slim Initiative for Genomic Medicine (SIGMA) project.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Pleuropulmonary Blastoma\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Pleuropulmonary_Blastoma","name":"Pleuropulmonary Blastoma","kind":"Disorder","source_path":"kb/disorders/Pleuropulmonary_Blastoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pleuropulmonary_Blastoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pleuropulmonary_Blastoma.html#dataset-dbgap-phs000543"}],"context_names":["Pleuropulmonary Blastoma"],"disease_names":["Pleuropulmonary Blastoma"],"disease_name":"Pleuropulmonary Blastoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Pleuropulmonary_Blastoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pleuropulmonary_Blastoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Pleuropulmonary_Blastoma.html#dataset-dbgap-phs000543"]},{"id":"dataset:dbgap:phs000562","accession":"dbgap:phs000562","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000562","title":"The Genetic Landscape of Mutations in Burkitt Lymphoma","alternate_titles":[],"description":"Burkitt lymphoma (BL) is characterized by deregulation of  MYC , but the contribution of other genetic mutations to the disease is largely unknown. We sequenced exomes of 59 BL tumors, 14 of which had paired normal tissue. Our work elucidates commonly occurring gene-coding mutations in Burkitt lymphoma and implicates  ID3  as a novel tumor suppressor gene.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Burkitt Lymphoma\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Burkitt_Lymphoma","name":"Burkitt Lymphoma","kind":"Disorder","source_path":"kb/disorders/Burkitt_Lymphoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Burkitt_Lymphoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Burkitt_Lymphoma.html#dataset-dbgap-phs000562"}],"context_names":["Burkitt Lymphoma"],"disease_names":["Burkitt Lymphoma"],"disease_name":"Burkitt Lymphoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Burkitt_Lymphoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Burkitt_Lymphoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Burkitt_Lymphoma.html#dataset-dbgap-phs000562"]},{"id":"dataset:dbgap:phs000563","accession":"dbgap:phs000563","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000563","title":"Pilocytic Astrocytoma in NF1","alternate_titles":[],"description":"Neurofibromatosis type 1 (NF1) inherited cancer predisposition syndrome is one of the most common autosomal dominant tumor predisposition syndromes in which affected individuals develop brain tumors. These low-grade glial neoplasms (pilocytic astrocytomas) typically arise in children younger than 7 years of age and are hypothesized to result from a combination of germline and acquired somatic NF1 tumor suppressor gene mutations.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Pilocytic Astrocytoma\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Pilocytic_Astrocytoma","name":"Pilocytic Astrocytoma","kind":"Disorder","source_path":"kb/disorders/Pilocytic_Astrocytoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pilocytic_Astrocytoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pilocytic_Astrocytoma.html#dataset-dbgap-phs000563"}],"context_names":["Pilocytic Astrocytoma"],"disease_names":["Pilocytic Astrocytoma"],"disease_name":"Pilocytic Astrocytoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Pilocytic_Astrocytoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pilocytic_Astrocytoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Pilocytic_Astrocytoma.html#dataset-dbgap-phs000563"]},{"id":"dataset:dbgap:phs000567","accession":"dbgap:phs000567","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000567","title":"NAB2-STAT6 Gene Fusions in Solitary Fibrous Tumor by Integrative Sequencing","alternate_titles":[],"description":"Transcriptome sequencing of solitary fibrous tumors / hemangiopericytomas from a variety of anatomic sites revealed recurrent gene fusions between two genes, NAB2 and STAT6. All SFTs examined exhibited an in-frame fusion transcript encoding a fusion protein containing the EGR1 interaction domain of NAB2 with the transcriptional activation domain of STAT6. Functional testing of the fusion alleles confirmed the conversion of the wt NAB2 repressor into a transcriptional activator.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Solitary Fibrous Tumor\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Solitary_Fibrous_Tumor","name":"Solitary Fibrous Tumor","kind":"Disorder","source_path":"kb/disorders/Solitary_Fibrous_Tumor.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Solitary_Fibrous_Tumor.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Solitary_Fibrous_Tumor.html#dataset-dbgap-phs000567"}],"context_names":["Solitary Fibrous Tumor"],"disease_names":["Solitary Fibrous Tumor"],"disease_name":"Solitary Fibrous Tumor","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Solitary_Fibrous_Tumor.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Solitary_Fibrous_Tumor.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Solitary_Fibrous_Tumor.html#dataset-dbgap-phs000567"]},{"id":"dataset:dbgap:phs000574","accession":"dbgap:phs000574","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000574","title":"Rett Syndrome Natural History Protocol","alternate_titles":[],"description":"This observational study will involve the comprehensive assessment of the clinical features of Rett syndrome with this Rare Diseases Clinical Research Network. A clinical database of 1350 individuals with Rett syndrome including MECP2 mutation status for the purpose of elaborating phenotype-genotype correlations will be established.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Rett Syndrome\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Rett_Syndrome","name":"Rett Syndrome","kind":"Disorder","source_path":"kb/disorders/Rett_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rett_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Rett_Syndrome.html#dataset-dbgap-phs000574"}],"context_names":["Rett Syndrome"],"disease_names":["Rett Syndrome"],"disease_name":"Rett Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Rett_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rett_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Rett_Syndrome.html#dataset-dbgap-phs000574"]},{"id":"dataset:dbgap:phs000581","accession":"dbgap:phs000581","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000581","title":"NHLBI GO-ESP: Family Studies (Dilated Cardiomyopathy)","alternate_titles":[],"description":"The NHLBI \"Grand Opportunity\" Exome Sequencing Project (GO-ESP), a signature project of the NHLBI Recovery Act investment, was designed to identify genetic variants in coding regions (exons) of the human genome (the \"exome\") that are associated with heart, lung and blood diseases. These and related diseases that are of high impact to public health and individuals from diverse racial and ethnic groups will be studied.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Dilated Cardiomyopathy\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Dilated_Cardiomyopathy","name":"Dilated Cardiomyopathy","kind":"Disorder","source_path":"kb/disorders/Dilated_Cardiomyopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dilated_Cardiomyopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy.html#dataset-dbgap-phs000581"}],"context_names":["Dilated Cardiomyopathy"],"disease_names":["Dilated Cardiomyopathy"],"disease_name":"Dilated Cardiomyopathy","same_context_model_ids":["model:kb/disorders/Dilated_Cardiomyopathy.yaml:Patient-specific TNNT2 R173W iPSC-derived cardiomyocytes (Clinical Trials in a Dish)"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Dilated_Cardiomyopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dilated_Cardiomyopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy.html#dataset-dbgap-phs000581"]},{"id":"dataset:dbgap:phs000586","accession":"dbgap:phs000586","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000586","title":"Genome Wide Association Studies in Alopecia Areata","alternate_titles":[],"description":"1054 unrelated alopecia areata patients were genotyped with the Illumina HumanHap550v3.0 genotyping chip. Allele frequencies were compared to publically available data from three population cohorts of controls.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Alopecia Areata\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Alopecia_Areata","name":"Alopecia Areata","kind":"Disorder","source_path":"kb/disorders/Alopecia_Areata.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alopecia_Areata.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Alopecia_Areata.html#dataset-dbgap-phs000586"}],"context_names":["Alopecia Areata"],"disease_names":["Alopecia Areata"],"disease_name":"Alopecia Areata","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Alopecia_Areata.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alopecia_Areata.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Alopecia_Areata.html#dataset-dbgap-phs000586"]},{"id":"dataset:dbgap:phs000588","accession":"dbgap:phs000588","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000588","title":"VCRC5502: Longitudinal Protocol for Giant Cell Arteritis","alternate_titles":[],"description":"The development and validation of accurate biological markers and predictors of disease activity and outcome for Giant Cell Arteritis, a form of idiopathic vasculitis, would have a major positive impact on the clinical care of patients with this rare disease, be an important insight into the design of clinical trials and feasibility of new drug development, and provide important insight into the pathogenesis of this condition.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Giant Cell Arteritis\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Giant_Cell_Arteritis","name":"Giant Cell Arteritis","kind":"Disorder","source_path":"kb/disorders/Giant_Cell_Arteritis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Giant_Cell_Arteritis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Giant_Cell_Arteritis.html#dataset-dbgap-phs000588"}],"context_names":["Giant Cell Arteritis"],"disease_names":["Giant Cell Arteritis"],"disease_name":"Giant Cell Arteritis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Giant_Cell_Arteritis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Giant_Cell_Arteritis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Giant_Cell_Arteritis.html#dataset-dbgap-phs000588"]},{"id":"dataset:dbgap:phs000605","accession":"dbgap:phs000605","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000605","title":"Multicenter International Lymphangioleiomyomatosis Efficacy of Sirolimus Trial (The MILES Trial)","alternate_titles":[],"description":"Lymphangioleiomyomatosis (LAM) is an uncommon, progressive, cystic lung disease that predominantly affects young women. It is believed to be caused by defects within cellular pathways that regulate nutrient uptake, cell size, cell migration, and cell proliferation. The disease is caused by mutations in tuberous sclerosis complex (TSC) genes. Individuals with Lymphangioleiomyomatosis (LAM) often experience pneumothorax and chylothorax, as well progressive loss of lung function.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Lymphangioleiomyomatosis\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Lymphangioleiomyomatosis","name":"Lymphangioleiomyomatosis","kind":"Disorder","source_path":"kb/disorders/Lymphangioleiomyomatosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Lymphangioleiomyomatosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Lymphangioleiomyomatosis.html#dataset-dbgap-phs000605"}],"context_names":["Lymphangioleiomyomatosis"],"disease_names":["Lymphangioleiomyomatosis"],"disease_name":"Lymphangioleiomyomatosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Lymphangioleiomyomatosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Lymphangioleiomyomatosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Lymphangioleiomyomatosis.html#dataset-dbgap-phs000605"]},{"id":"dataset:dbgap:phs000612","accession":"dbgap:phs000612","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000612","title":"The mutational characterization of adenoid cystic carcinoma","alternate_titles":[],"description":"Adenoid cystic carcinoma (ACC) typically emanate from the major and minor salivary glands of the head and neck. ACCs have high rates of perineural invasion, locoregional recurrence, and distant metastasis. Here we report sequencing of 60 tumor/normal pairs and find substantial mutational diversity. On pathway analysis, a significant percentage of mutations involved chromatin remodeling, DNA damage, protein kinase A signaling, and FGF/IGF/PI3K signaling. Whole genome sequencing and FISH confirmed the MYB-NFIB translocation as the main structural variant in ACC.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Adenoid Cystic Carcinoma\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Adenoid_Cystic_Carcinoma","name":"Adenoid Cystic Carcinoma","kind":"Disorder","source_path":"kb/disorders/Adenoid_Cystic_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Adenoid_Cystic_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Adenoid_Cystic_Carcinoma.html#dataset-dbgap-phs000612"}],"context_names":["Adenoid Cystic Carcinoma"],"disease_names":["Adenoid Cystic Carcinoma"],"disease_name":"Adenoid Cystic Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Adenoid_Cystic_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Adenoid_Cystic_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Adenoid_Cystic_Carcinoma.html#dataset-dbgap-phs000612"]},{"id":"dataset:dbgap:phs000671","accession":"dbgap:phs000671","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000671","title":"Somatic Mutations in Variant and IGHV4-34 Expressing Hairy Cell Leukemia","alternate_titles":[],"description":"To understand the genetic mechanisms driving variant and IGHV4-34 expressing hairy-cell leukemia, we performed whole exome sequencing of tumor/normal pairs from ten patients.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Hairy Cell Leukemia\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Hairy_Cell_Leukemia","name":"Hairy Cell Leukemia","kind":"Disorder","source_path":"kb/disorders/Hairy_Cell_Leukemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hairy_Cell_Leukemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hairy_Cell_Leukemia.html#dataset-dbgap-phs000671"}],"context_names":["Hairy Cell Leukemia"],"disease_names":["Hairy Cell Leukemia"],"disease_name":"Hairy Cell Leukemia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hairy_Cell_Leukemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hairy_Cell_Leukemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hairy_Cell_Leukemia.html#dataset-dbgap-phs000671"]},{"id":"dataset:dbgap:phs000720","accession":"dbgap:phs000720","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000720","title":"Comprehensive genomic analysis of rhabdomyosarcoma — WGS, WES, and RNA-seq of primary human tumors (Shern et al. 2014 Cancer Discovery)","alternate_titles":[],"description":"Reference multi-platform genomic landscape study of primary human rhabdomyosarcoma. Includes WGS (44 tumor/normal pairs at ~105× depth), WES (103 tumor/normal pairs), RNA-seq (80 tumors), and SNP arrays (865 consented subjects in dbGaP v5). PAX3-FOXO1 (n≈35) and PAX7-FOXO1 (n≈15) fusion-positive cases dominate the cohort. Establishes that the RTK/RAS/PIK3CA genetic axis is altered in 93% of cases, revealing a framework for genomics-directed therapy. Identifies the recurrent secondary somatic landscape (MYCN amplification, CDK4/CDKN2A alterations, TP53 mutations) co-occurring with PAX fusions. Publicly accessible mutation summary and expression data via cBioPortal study rms_nih_2014; raw BAM/VCF files require dbGaP controlled-access approval.","alternate_descriptions":[],"data_types":["MULTI_OMICS"],"data_type_labels":["Multi Omics"],"data_type_label":"Multi Omics","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0001134","label":"skeletal muscle tissue","display_label":"skeletal muscle tissue","url":"http://purl.obolibrary.org/obo/UBERON_0001134"}],"sample_type_labels":["skeletal muscle tissue"],"sample_counts":[147],"sample_count":147,"conditions":["fusion-positive rhabdomyosarcoma (PAX3-FOXO1 and PAX7-FOXO1)","fusion-negative rhabdomyosarcoma"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["Illumina HiSeq 2000; Illumina Omni 2.5M/5M SNP arrays"],"platform":"Illumina HiSeq 2000; Illumina Omni 2.5M/5M SNP arrays","publications":["PMID:24436047"],"publication_contexts":[{"context_id":"disorder:Alveolar_Rhabdomyosarcoma","publication":"PMID:24436047"}],"publication":"PMID:24436047","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/24436047","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:24436047","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/24436047","reference_title":"Comprehensive genomic analysis of rhabdomyosarcoma reveals a landscape of alterations affecting a common genetic axis in fusion-positive and fusion-negative tumors.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"Here, we report a collaborative effort between the National Cancer Institute, the Children's Oncology Group, and the Broad Institute using a combination of whole-genome, whole-exome and whole-transcriptome sequencing along with high resolution SNP arrays to characterize the landscape of somatic alterations in 147 tumor/normal pairs.","explanation":"Directly supports the multi-platform design, collaborators, and cohort size represented by this dbGaP record."}],"notes":["dbGaP accession phs000720 (currently v5.p2). Open summary-level mutation and expression data accessible via cBioPortal study rms_nih_2014 (https://www.cbioportal.org/study/summary?id=rms_nih_2014). This is the same study cited in the genetic and pathophysiology sections (PMID:24436047); the dataset entry enables direct linkage to the raw data repository."],"contexts":[{"id":"disorder:Alveolar_Rhabdomyosarcoma","name":"Alveolar Rhabdomyosarcoma","kind":"Disorder","source_path":"kb/disorders/Alveolar_Rhabdomyosarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alveolar_Rhabdomyosarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Alveolar_Rhabdomyosarcoma.html#dataset-dbgap-phs000720"}],"context_names":["Alveolar Rhabdomyosarcoma"],"disease_names":["Alveolar Rhabdomyosarcoma"],"disease_name":"Alveolar Rhabdomyosarcoma","same_context_model_ids":["model:kb/disorders/Alveolar_Rhabdomyosarcoma.yaml:Fusion-positive RMS cancer-associated fibroblast coculture","model:kb/disorders/Alveolar_Rhabdomyosarcoma.yaml:Patient-derived ARMS single-cell culture model"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Alveolar_Rhabdomyosarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alveolar_Rhabdomyosarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Alveolar_Rhabdomyosarcoma.html#dataset-dbgap-phs000720"]},{"id":"dataset:dbgap:phs000726","accession":"dbgap:phs000726","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000726","title":"Genome-wide Association Study of Myasthenia Gravis","alternate_titles":[],"description":"The purpose of this project was to conduct a genome-wide associate study to search for the genetic factors that predispose to myasthenia gravis. The rationale for this study lies in the fact that, although the immunological and physiological processes affecting the neuromuscular junctions of myasthenia gravis patients are well understood, the spectrum of genetic factors that predispose to myasthenia gravis and influence its disease manifestations are not well known.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Myasthenia Gravis\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Myasthenia_Gravis","name":"Myasthenia Gravis","kind":"Disorder","source_path":"kb/disorders/Myasthenia_Gravis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myasthenia_Gravis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Myasthenia_Gravis.html#dataset-dbgap-phs000726"}],"context_names":["Myasthenia Gravis"],"disease_names":["Myasthenia Gravis"],"disease_name":"Myasthenia Gravis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Myasthenia_Gravis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myasthenia_Gravis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Myasthenia_Gravis.html#dataset-dbgap-phs000726"]},{"id":"dataset:dbgap:phs000729","accession":"dbgap:phs000729","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000729","title":"Follicular Lymphoma 2013 - Malek","alternate_titles":[],"description":"A cohort of follicular lymphoma cases had tumor cells purified from tissue samples after informed consent using flow cytometry. DNA was extracted from the cells, and samples were subjected to solution-based exome capture using the Illumina TruSeq Exome Enrichment Kit and the Illumina HiSeq 2000 platform.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Follicular Lymphoma\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Follicular_Lymphoma","name":"Follicular Lymphoma","kind":"Disorder","source_path":"kb/disorders/Follicular_Lymphoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Follicular_Lymphoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Follicular_Lymphoma.html#dataset-dbgap-phs000729"}],"context_names":["Follicular Lymphoma"],"disease_names":["Follicular Lymphoma"],"disease_name":"Follicular Lymphoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Follicular_Lymphoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Follicular_Lymphoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Follicular_Lymphoma.html#dataset-dbgap-phs000729"]},{"id":"dataset:dbgap:phs000785","accession":"dbgap:phs000785","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000785","title":"Sequencing Analysis of Cutaneous Squamous Cell Carcinoma","alternate_titles":[],"description":"The Exome Sequencing Analysis of Cutaneous Squamous Cell Carcinoma (SCC) study is a single-center cohort study. To identify recurrent genomic aberrations that might underlie the development of this malignancy, we performed whole exome sequencing on a series of SCC-normal pairs to distill a list of 336 candidate genes that were subsequently re-sequenced in 100 SCC-normal pairs with an average depth >1200X. This study also included whole-genome copy number analysis on 5 primary SCC with KNSTRN p.Ser24Phe and 5 histologically matched SCC with wild-type KNSTRN.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Cutaneous Squamous Cell Carcinoma\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Cutaneous_Squamous_Cell_Carcinoma","name":"Cutaneous Squamous Cell Carcinoma","kind":"Disorder","source_path":"kb/disorders/Cutaneous_Squamous_Cell_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cutaneous_Squamous_Cell_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cutaneous_Squamous_Cell_Carcinoma.html#dataset-dbgap-phs000785"}],"context_names":["Cutaneous Squamous Cell Carcinoma"],"disease_names":["Cutaneous Squamous Cell Carcinoma"],"disease_name":"Cutaneous Squamous Cell Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cutaneous_Squamous_Cell_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cutaneous_Squamous_Cell_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cutaneous_Squamous_Cell_Carcinoma.html#dataset-dbgap-phs000785"]},{"id":"dataset:dbgap:phs000790","accession":"dbgap:phs000790","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000790","title":"Comparative Analysis of Primary and Metastatic Colorectal Cancer","alternate_titles":[],"description":"Molecular profiling for somatic mutations that predict response to anti-EGFR therapy in colorectal cancer (CRC) has become standard practice. However, abundant tissue from metastatic lesions is not always available from patients with metastatic CRC. Concerns involving genetic heterogeneity between primary and metastatic lesions have called into question the suitability of profiling primary tumors in patients with metastatic disease.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Metastatic Colorectal Cancer\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Colon_Adenocarcinoma","name":"Colon Adenocarcinoma","kind":"Disorder","source_path":"kb/disorders/Colon_Adenocarcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Colon_Adenocarcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Colon_Adenocarcinoma.html#dataset-dbgap-phs000790"}],"context_names":["Colon Adenocarcinoma"],"disease_names":["Colon Adenocarcinoma"],"disease_name":"Colon Adenocarcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Colon_Adenocarcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Colon_Adenocarcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Colon_Adenocarcinoma.html#dataset-dbgap-phs000790"]},{"id":"dataset:dbgap:phs000797","accession":"dbgap:phs000797","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000797","title":"CTLA4 haploinsufficiency and immune dysregulation","alternate_titles":[],"description":"We identified germline heterozygous mutations in  CTLA4  in members of four families with severe immune dysregulation. Human  CTLA4  haploinsufficiency caused dysregulation of FoxP3+ regulatory T (Treg) cells and lymphocytic infiltration of target organs, mimicking  Ctla4  homozygous mice. Patients also exhibited a B cell phenotype, with progressive loss of B cells and accumulation of autoreactive CD21 lo  B cells. This study demonstrates a critical quantitative role for CTLA-4 in human immune homeostasis.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Human family sequencing study underlying the discovery of germline CTLA4-associated immune dysregulation. Individual-level genomic data are subject to repository access controls."],"contexts":[{"id":"disorder:CTLA4_Haploinsufficiency","name":"CTLA4 Haploinsufficiency","kind":"Disorder","source_path":"kb/disorders/CTLA4_Haploinsufficiency.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/CTLA4_Haploinsufficiency.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/CTLA4_Haploinsufficiency.html#dataset-dbgap-phs000797"}],"context_names":["CTLA4 Haploinsufficiency"],"disease_names":["CTLA4 Haploinsufficiency"],"disease_name":"CTLA4 Haploinsufficiency","same_context_model_ids":["model:kb/disorders/CTLA4_Haploinsufficiency.yaml:CHO cells expressing CTLA4 variants","model:kb/disorders/CTLA4_Haploinsufficiency.yaml:CTLA4 knockdown and rescue in human lymphocytes","model:kb/disorders/CTLA4_Haploinsufficiency.yaml:Gene-edited patient T cells","model:kb/disorders/CTLA4_Haploinsufficiency.yaml:HEK293T Phe56Cys functional assays","model:kb/disorders/CTLA4_Haploinsufficiency.yaml:Patient Treg suppression coculture"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/CTLA4_Haploinsufficiency.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/CTLA4_Haploinsufficiency.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/CTLA4_Haploinsufficiency.html#dataset-dbgap-phs000797"]},{"id":"dataset:dbgap:phs000804","accession":"dbgap:phs000804","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000804","title":"Genomic Sequencing of Ewing Sarcoma","alternate_titles":[],"description":"Pediatric Ewing sarcoma is a pediatric cancer that primarily arises from the bone. It is characterized by chimeric fusions of the EWS gene and an ETS family transcription factor. In this study, we performed massively parallel sequencing of a larger collection of Ewing sarcoma tumors to define the genomic landscape of this disease. We found that these tumors are among of the most genetically normal cancers currently characterized. There was also a marked absence of recurrent mutations in immediately targetable signaling transduction pathway genes.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Ewing Sarcoma\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Ewing_Sarcoma","name":"Ewing Sarcoma","kind":"Disorder","source_path":"kb/disorders/Ewing_Sarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ewing_Sarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#dataset-dbgap-phs000804"}],"context_names":["Ewing Sarcoma"],"disease_names":["Ewing Sarcoma"],"disease_name":"Ewing Sarcoma","same_context_model_ids":["model:kb/disorders/Ewing_Sarcoma.yaml:BARD1-variant PSaRC318 and BARD1-depleted Ewing cells","model:kb/disorders/Ewing_Sarcoma.yaml:Ewing sarcoma tumor organoid model systems","model:kb/disorders/Ewing_Sarcoma.yaml:Flow-perfusion Ewing sarcoma 3D scaffold coculture","model:kb/disorders/Ewing_Sarcoma.yaml:Human embryonic mesenchymal stem cell EWS-FLI1 transformation model","model:kb/disorders/Ewing_Sarcoma.yaml:Patient-derived Ewing sarcoma culture panel"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Ewing_Sarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ewing_Sarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#dataset-dbgap-phs000804"]},{"id":"dataset:dbgap:phs000862","accession":"dbgap:phs000862","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000862","title":"Immune Response to IT ERT in Mucopolysaccharidosis I Patient","alternate_titles":[],"description":"In this study we characterized the immune response to intrathecal (IT) recombinant human alpha-L-iduronidase (rhIDU) in mucopolysaccharidosis I (MPS I) subjects with spinal cord compression who had been previously treated with intravenous rhIDU. Concentrations of specific antibodies and cytokines were measured in serum and cerebrospinal fluid (CSF) collected before monthly IT rhIDU infusions. These serologic findings were compared with clinical adverse event (AE) reports to establish temporal correlations with clinical symptoms.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Mucopolysaccharidosis\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Mucopolysaccharidosis","name":"Mucopolysaccharidosis","kind":"Disorder","source_path":"kb/disorders/Mucopolysaccharidosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mucopolysaccharidosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Mucopolysaccharidosis.html#dataset-dbgap-phs000862"}],"context_names":["Mucopolysaccharidosis"],"disease_names":["Mucopolysaccharidosis"],"disease_name":"Mucopolysaccharidosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Mucopolysaccharidosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mucopolysaccharidosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Mucopolysaccharidosis.html#dataset-dbgap-phs000862"]},{"id":"dataset:dbgap:phs000866","accession":"dbgap:phs000866","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000866","title":"Family Genomics of Bipolar Disorder","alternate_titles":[],"description":"This study examined the segregation of variants with phenotype in pedigrees harboring bipolar disorder.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Bipolar Disorder\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Bipolar_Disorder","name":"Bipolar Disorder","kind":"Disorder","source_path":"kb/disorders/Bipolar_Disorder.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bipolar_Disorder.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Bipolar_Disorder.html#dataset-dbgap-phs000866"}],"context_names":["Bipolar Disorder"],"disease_names":["Bipolar Disorder"],"disease_name":"Bipolar Disorder","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Bipolar_Disorder.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bipolar_Disorder.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Bipolar_Disorder.html#dataset-dbgap-phs000866"]},{"id":"dataset:dbgap:phs000904","accession":"dbgap:phs000904","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000904","title":"APC Promoter Deletion in Classic Familial Adenomatous Polyposis","alternate_titles":[],"description":"The ~80% of individuals with classic familial adenomatous polyposis (FAP) have detectable mutations in the coding sequence of the adenomatous polyposis coli (APC) gene. To investigate the 20% of families without detectable causative mutations, we used exome sequencing and second-generation sequencing of the APC locus including non-coding regions. We identified a novel ~11kb deletion 44kb upstream of APC that was present only in affected individuals of three kindreds.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Familial Adenomatous Polyposis\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Familial_Adenomatous_Polyposis","name":"Familial Adenomatous Polyposis","kind":"Disorder","source_path":"kb/disorders/Familial_Adenomatous_Polyposis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Familial_Adenomatous_Polyposis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Familial_Adenomatous_Polyposis.html#dataset-dbgap-phs000904"}],"context_names":["Familial Adenomatous Polyposis"],"disease_names":["Familial Adenomatous Polyposis"],"disease_name":"Familial Adenomatous Polyposis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Familial_Adenomatous_Polyposis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Familial_Adenomatous_Polyposis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Familial_Adenomatous_Polyposis.html#dataset-dbgap-phs000904"]},{"id":"dataset:dbgap:phs000913","accession":"dbgap:phs000913","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000913","title":"Genomic Analysis of Mycosis Fungoides and Sézary Syndrome","alternate_titles":[],"description":"Mycosis Fungoides (MF) and Sézary Syndrome (Sz) comprise the majority of Cutaneous T-Cell Lymphoma (CTCL) cases and are characterized by clinical heterogeneity. This array of symptoms includes skin patches, plaques and tumors as well as blood involvement and erythroderma. Because the genetic basis of CTCL is still poorly understood, we performed whole-exome sequencing on 11 MF/Sz samples and their matched, normal control DNA. Upon analyzing this data, we distilled a list of an additional 494 genes to be sequenced at depth.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Mycosis Fungoides\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Mycosis_Fungoides","name":"Mycosis Fungoides","kind":"Disorder","source_path":"kb/disorders/Mycosis_Fungoides.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mycosis_Fungoides.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Mycosis_Fungoides.html#dataset-dbgap-phs000913"}],"context_names":["Mycosis Fungoides"],"disease_names":["Mycosis Fungoides"],"disease_name":"Mycosis Fungoides","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Mycosis_Fungoides.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mycosis_Fungoides.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Mycosis_Fungoides.html#dataset-dbgap-phs000913"]},{"id":"dataset:dbgap:phs000917","accession":"dbgap:phs000917","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000917","title":"Pakistan Risk of Myocardial Infarction Study (PROMIS) human knockout cohort","alternate_titles":[],"description":"Whole-exome sequencing of 10,503 adult PROMIS participants identified six adults homozygous for a predicted TREH splice-acceptor deletion. The cohort was assembled for cardiometabolic research rather than trehalase deficiency, and no trehalose challenge or intestinal-enzyme phenotype was reported for the TREH homozygotes.","alternate_descriptions":[],"data_types":["WES"],"data_type_labels":["Whole exome sequencing"],"data_type_label":"Whole exome sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[10503],"sample_count":10503,"conditions":["Broad adult cardiometabolic cohort"],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:12266","label":"TREH","display_label":"TREH","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/12266"}],"genes":["TREH"],"platforms":[],"platform":null,"publications":["PMID:28406212"],"publication_contexts":[{"context_id":"disorder:Trehalase_Deficiency","publication":"PMID:28406212"}],"publication":"PMID:28406212","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/28406212","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"url:https://www.ebi.ac.uk/europepmc/webservices/rest/PMC5600291/fullTextXML","reference_url":null,"reference_title":"Methods","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"Here, we sequenced the protein-coding regions of 10,503 adult participants in the Pakistan Risk of Myocardial Infarction Study (PROMIS)","explanation":"Supports study design and sample count."},{"reference":"url:https://www.ebi.ac.uk/europepmc/webservices/rest/PMC5600291/fullTextXML","reference_url":null,"reference_title":"Methods","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"DNA sequences have been deposited with the NIH dbGAP repository under accession numbers phs000917.","explanation":"Supports the public controlled-access dataset identifier."}],"notes":["Direct variant-cohort relevance, not a disease-specific natural-history dataset. Sequence data are controlled-access through dbGaP."],"contexts":[{"id":"disorder:Trehalase_Deficiency","name":"Trehalase Deficiency","kind":"Disorder","source_path":"kb/disorders/Trehalase_Deficiency.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Trehalase_Deficiency.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Trehalase_Deficiency.html#dataset-dbgap-phs000917"}],"context_names":["Trehalase Deficiency"],"disease_names":["Trehalase Deficiency"],"disease_name":"Trehalase Deficiency","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Trehalase_Deficiency.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Trehalase_Deficiency.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Trehalase_Deficiency.html#dataset-dbgap-phs000917"]},{"id":"dataset:dbgap:phs000926","accession":"dbgap:phs000926","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000926","title":"Rare disease susceptibility alleles in children with Crohn disease","alternate_titles":[],"description":"The overall goal of this proposed project is to identify rare genetic variants contributing to childhood onset-Crohn disease. Crohn disease is a chronic inflammatory disorder of the gastrointestinal tract of unclear etiology and no known cure. Affected children suffer from diarrhea, abdominal pain, growth disturbances, and an impaired quality of life. The identified Crohn disease susceptibility alleles have improved our understanding of Crohn disease pathogenesis.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Crohn Disease\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Crohn_Disease","name":"Crohn Disease","kind":"Disorder","source_path":"kb/disorders/Crohn_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Crohn_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Crohn_Disease.html#dataset-dbgap-phs000926"}],"context_names":["Crohn Disease"],"disease_names":["Crohn Disease"],"disease_name":"Crohn Disease","same_context_model_ids":["model:kb/disorders/Crohn_Disease.yaml:Enteroendocrine-deficient intestinal enteroid barrier model","model:kb/disorders/Crohn_Disease.yaml:Primary human small-intestinal monolayer barrier model","model:kb/disorders/Crohn_Disease.yaml:PSC-derived intestinal organoid-macrophage coculture model"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Crohn_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Crohn_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Crohn_Disease.html#dataset-dbgap-phs000926"]},{"id":"dataset:dbgap:phs000966","accession":"dbgap:phs000966","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000966","title":"Family Study of Essential Tremor (FASET)","alternate_titles":[],"description":"The Familial Study of Essential Tremor (FASET) was designed to identify susceptibility genes for Essential Tremor. ET is among the most common neurological diseases with a prevalence (age > 40 years) estimated to be 4.0% and prevalence in advanced age (' 90 years) exceeding 20%. ET, often referred to as \"familial tremor\", is generally regarded as a highly genetic disorder with families with affecteds over multiple generations, and twin studies showing high concordance among monozygotic twins. Probands (affected with ET) and relatives were enrolled in a family study of ET at Columbia","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Essential Tremor\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Essential_Tremor","name":"Essential Tremor","kind":"Disorder","source_path":"kb/disorders/Essential_Tremor.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Essential_Tremor.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Essential_Tremor.html#dataset-dbgap-phs000966"}],"context_names":["Essential Tremor"],"disease_names":["Essential Tremor"],"disease_name":"Essential Tremor","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Essential_Tremor.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Essential_Tremor.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Essential_Tremor.html#dataset-dbgap-phs000966"]},{"id":"dataset:dbgap:phs000973","accession":"dbgap:phs000973","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000973","title":"The Genomic Landscape of Juvenile Myelomonocytic Leukemia","alternate_titles":[],"description":"This study analyzed samples from 29 patients with juvenile myelomonocytic leukemia (JMML) using whole exome sequencing. Each patient had a paired germline tissue along with a diagnostic leukemia sample. Germline tissue types included buccal mucosa, cordblood, Epstein-Barr virus immortalized cell lines and fibroblasts from either skin or bone marrow. Leukemia samples were either blood or bone marrow. Seven of the 29 patients also had a relapsed leukemia sample available for exome analysis.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Juvenile Myelomonocytic Leukemia\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Juvenile_Myelomonocytic_Leukemia","name":"Juvenile Myelomonocytic Leukemia","kind":"Disorder","source_path":"kb/disorders/Juvenile_Myelomonocytic_Leukemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Juvenile_Myelomonocytic_Leukemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Juvenile_Myelomonocytic_Leukemia.html#dataset-dbgap-phs000973"}],"context_names":["Juvenile Myelomonocytic Leukemia"],"disease_names":["Juvenile Myelomonocytic Leukemia"],"disease_name":"Juvenile Myelomonocytic Leukemia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Juvenile_Myelomonocytic_Leukemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Juvenile_Myelomonocytic_Leukemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Juvenile_Myelomonocytic_Leukemia.html#dataset-dbgap-phs000973"]},{"id":"dataset:dbgap:phs000982","accession":"dbgap:phs000982","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000982","title":"Genetic Analysis of Psoriasis and Psoriatic Arthritis","alternate_titles":[],"description":"This study is a genome-wide study of genetic associations with psoriatic arthritis (PsA), an inflammatory musculoskeletal condition that develops in up to 30% of people who have chronic psoriasis skin lesions. 1,526 cases affected with psoriatic arthritis and 1,508 unaffected controls were recruited and typed on the Illumina HumanOmni1-Quad BeadChip array. After application of quality control measures to both samples and SNPs, genotypes for 791,217 autosomal SNPs were available for 1,430 PsA cases and 1,417 controls.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Psoriatic Arthritis\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Psoriatic_Arthritis","name":"Psoriatic Arthritis","kind":"Disorder","source_path":"kb/disorders/Psoriatic_Arthritis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Psoriatic_Arthritis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Psoriatic_Arthritis.html#dataset-dbgap-phs000982"}],"context_names":["Psoriatic Arthritis"],"disease_names":["Psoriatic Arthritis"],"disease_name":"Psoriatic Arthritis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Psoriatic_Arthritis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Psoriatic_Arthritis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Psoriatic_Arthritis.html#dataset-dbgap-phs000982"]},{"id":"dataset:dbgap:phs000987","accession":"dbgap:phs000987","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000987","title":"Whole Exome Sequence of 184 Individuals with 22q11.2 Deletion Syndrome","alternate_titles":[],"description":"Our goal is to find genetic modifiers of major phenotypes in patients with 22q11.2 deletion syndrome, also known as DiGeorge syndrome or velo-cardio-facial syndrome. Whole exome sequencing was performed as part of a contract to the NHLBI, Resequencing and Genotyping Service. We have obtained cardiac phenotype information from the de-identified subjects enrolled in the study, either by echocardiography report or medical doctor report. All of the subjects have a 3 million base pair 22q11.2 deletion flanked by low copy repeats, LCR22, A-D.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"22q11.2 Deletion Syndrome\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:22q11.2_Deletion_Syndrome","name":"22q11.2 Deletion Syndrome","kind":"Disorder","source_path":"kb/disorders/22q11.2_Deletion_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/22q11.2_Deletion_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/22q11.2_Deletion_Syndrome.html#dataset-dbgap-phs000987"}],"context_names":["22q11.2 Deletion Syndrome"],"disease_names":["22q11.2 Deletion Syndrome"],"disease_name":"22q11.2 Deletion Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/22q11.2_Deletion_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/22q11.2_Deletion_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/22q11.2_Deletion_Syndrome.html#dataset-dbgap-phs000987"]},{"id":"dataset:dbgap:phs000994","accession":"dbgap:phs000994","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000994","title":"The Mutational Landscape of CTCL and Sezary Syndrome.","alternate_titles":[],"description":"Sezary syndrome is a leukemic and aggressive form of cutaneous T-cell lymphoma (CTCL) resulting from the malignant transformation of skin-homing central memory CD4+ T cells. To identify new genetic alterations involved in Sezary syndrome and CTCL transformation we performed whole-exome sequencing of tumor-normal sample pairs from 26 Sezary syndrome and 16 CTCL patients.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Sezary Syndrome\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Sezary_Syndrome","name":"Sezary Syndrome","kind":"Disorder","source_path":"kb/disorders/Sezary_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sezary_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Sezary_Syndrome.html#dataset-dbgap-phs000994"}],"context_names":["Sezary Syndrome"],"disease_names":["Sezary Syndrome"],"disease_name":"Sezary Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Sezary_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sezary_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Sezary_Syndrome.html#dataset-dbgap-phs000994"]},{"id":"dataset:dbgap:phs001080","accession":"dbgap:phs001080","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001080","title":"Genome Studies in Hereditary Spastic Paraplegia","alternate_titles":[],"description":"Next-generation sequencing technology is opening up new opportunities to rethink the way we identify disease causing genetic variation. An early application, whole exome sequencing, has now been established by a small number of research labs, including ours. Exome sequencing allows obtaining a near complete set of protein coding genomic variation in single individuals for less than $5,000. Promising targets for exome sequencing studies are Mendelian diseases, such as hereditary spastic paraplegias (HSP).","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Hereditary Spastic Paraplegia\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Hereditary_Spastic_Paraplegia","name":"Hereditary Spastic Paraplegia","kind":"Disorder","source_path":"kb/disorders/Hereditary_Spastic_Paraplegia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hereditary_Spastic_Paraplegia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hereditary_Spastic_Paraplegia.html#dataset-dbgap-phs001080"}],"context_names":["Hereditary Spastic Paraplegia"],"disease_names":["Hereditary Spastic Paraplegia"],"disease_name":"Hereditary Spastic Paraplegia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hereditary_Spastic_Paraplegia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hereditary_Spastic_Paraplegia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hereditary_Spastic_Paraplegia.html#dataset-dbgap-phs001080"]},{"id":"dataset:dbgap:phs001183","accession":"dbgap:phs001183","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001183","title":"Epi4K: Gene Discovery in 4,000 Epilepsy Genomes: Genetic Analyses in Periventricular Nodular Heterotopia","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Periventricular Nodular Heterotopia\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Periventricular_Nodular_Heterotopia","name":"Periventricular Nodular Heterotopia","kind":"Disorder","source_path":"kb/disorders/Periventricular_Nodular_Heterotopia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Periventricular_Nodular_Heterotopia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Periventricular_Nodular_Heterotopia.html#dataset-dbgap-phs001183"}],"context_names":["Periventricular Nodular Heterotopia"],"disease_names":["Periventricular Nodular Heterotopia"],"disease_name":"Periventricular Nodular Heterotopia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Periventricular_Nodular_Heterotopia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Periventricular_Nodular_Heterotopia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Periventricular_Nodular_Heterotopia.html#dataset-dbgap-phs001183"]},{"id":"dataset:dbgap:phs001207","accession":"dbgap:phs001207","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001207","title":"NHLBI TOPMed: African American Sarcoidosis Genetics Resource","alternate_titles":[],"description":"This study aims to comprehensively interrogate the genomes of African American sarcoidosis families. Sarcoidosis is characterized by a hyperimmune response resulting in granuloma formation in multiple organs. It affects African Americans (AAs) more frequently and more severely than whites. While previous linkage, admixture, candidate gene and genome-wide association (GWA) studies show statistically compelling effects, causal variants are still unknown and much of sarcoidosis heritability is yet to be explained.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Sarcoidosis\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Sarcoidosis","name":"Sarcoidosis","kind":"Disorder","source_path":"kb/disorders/Sarcoidosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sarcoidosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Sarcoidosis.html#dataset-dbgap-phs001207"}],"context_names":["Sarcoidosis"],"disease_names":["Sarcoidosis"],"disease_name":"Sarcoidosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Sarcoidosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sarcoidosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Sarcoidosis.html#dataset-dbgap-phs001207"]},{"id":"dataset:dbgap:phs001229","accession":"dbgap:phs001229","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001229","title":"Sequencing Follicular Lymphoma","alternate_titles":[],"description":"We performed exome sequencing of tumor (lymph node) and normal (skin) frozen tissue pairs from 24 patients in a discovery cohort with untreated follicular lymphoma (FL), relapsed FL, or transformed FL/iNHL (indolent non-Hodgkin lymphoma). From 24 patients, 28 tumor samples were exome sequenced including 1 patient with both untreated and relapse samples and 3 patients with samples derived from both bulk lymph node and following flow-sorting to purify light chain-restricted CD19+ lymphoma cells.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Follicular Lymphoma\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Follicular_Lymphoma","name":"Follicular Lymphoma","kind":"Disorder","source_path":"kb/disorders/Follicular_Lymphoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Follicular_Lymphoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Follicular_Lymphoma.html#dataset-dbgap-phs001229"}],"context_names":["Follicular Lymphoma"],"disease_names":["Follicular Lymphoma"],"disease_name":"Follicular Lymphoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Follicular_Lymphoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Follicular_Lymphoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Follicular_Lymphoma.html#dataset-dbgap-phs001229"]},{"id":"dataset:dbgap:phs001279","accession":"dbgap:phs001279","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001279","title":"Cross-Sectional Characterization of Idiopathic Bronchiectasis","alternate_titles":[],"description":"This GDMCC protocol will study adult patients with non-CF, idiopathic bronchiectasis, whose genetic etiologies are not known. Idiopathic bronchiectasis is reportedly more common in females with certain tall, thin body types and associated with environmental organisms, such as nontuberculous mycobacterium (NTM). The other susceptibility factors predisposing to bronchiectasis or acquisition of NTM are unclear. The study will attempt to broaden the understanding of this disease by comparing gender-associated factors and NTM status.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Bronchiectasis\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Bronchiectasis","name":"Bronchiectasis","kind":"Disorder","source_path":"kb/disorders/Bronchiectasis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bronchiectasis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Bronchiectasis.html#dataset-dbgap-phs001279"}],"context_names":["Bronchiectasis"],"disease_names":["Bronchiectasis"],"disease_name":"Bronchiectasis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Bronchiectasis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bronchiectasis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Bronchiectasis.html#dataset-dbgap-phs001279"]},{"id":"dataset:dbgap:phs001282","accession":"dbgap:phs001282","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001282","title":"Genomics of Endemic Burkitt Lymphoma","alternate_titles":[],"description":"This genomic landscape of Burkitt lymphoma represents a multimodal sequencing of tumors and control tissues and individuals to better understand the etiology, and molecular pathogenesis of Burkitt lymphoma including the roles of the associated Plasmodium falciparum malaria and EBV infections. Comprehensive sequencing set includes genomic, transcriptomic, and epigenomic datasets in concert with variable clinical phenotypes and outcome information such as anatomical presentation site, in-hospital survival rates, and EBV genome type.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Burkitt Lymphoma\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Burkitt_Lymphoma","name":"Burkitt Lymphoma","kind":"Disorder","source_path":"kb/disorders/Burkitt_Lymphoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Burkitt_Lymphoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Burkitt_Lymphoma.html#dataset-dbgap-phs001282"}],"context_names":["Burkitt Lymphoma"],"disease_names":["Burkitt Lymphoma"],"disease_name":"Burkitt Lymphoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Burkitt_Lymphoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Burkitt_Lymphoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Burkitt_Lymphoma.html#dataset-dbgap-phs001282"]},{"id":"dataset:dbgap:phs001284","accession":"dbgap:phs001284","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001284","title":"NCI Waldenstrom Macroglobulinemia Genome-wide Association Study","alternate_titles":[],"description":"A discovery GWAS is performed, consisting of genotyping 221 Waldenstrom macroglobulinemia (WM) cases on the Illumina Omni Express 12v1.1 platform and analyzing the genotypes together with those of 3798 previously genotyped controls in a model taking into account gender, age, and principal components of ancestry (i.e., significant eigenvectors). Directly genotyped data are supplemented by imputation using the Haplotype Reference Consortium.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Waldenstrom Macroglobulinemia\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Waldenstrom_Macroglobulinemia","name":"Waldenstrom Macroglobulinemia","kind":"Disorder","source_path":"kb/disorders/Waldenstrom_Macroglobulinemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Waldenstrom_Macroglobulinemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Waldenstrom_Macroglobulinemia.html#dataset-dbgap-phs001284"}],"context_names":["Waldenstrom Macroglobulinemia"],"disease_names":["Waldenstrom Macroglobulinemia"],"disease_name":"Waldenstrom Macroglobulinemia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Waldenstrom_Macroglobulinemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Waldenstrom_Macroglobulinemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Waldenstrom_Macroglobulinemia.html#dataset-dbgap-phs001284"]},{"id":"dataset:dbgap:phs001317","accession":"dbgap:phs001317","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001317","title":"Long-Term Outcome in Offspring and Mothers of Dexamethasone-Treated Pregnancies at Risk for Classical Congenital Adrenal Hyperplasia Owing to 21-Hydroxylase Deficiency","alternate_titles":[],"description":"Summary    The purpose of this study is to perform the first long-term follow up study both of adolescents and young adults with a history of prenatal treatment with dexamethasone and of their mothers and to test for adverse medical or behavioral side effects. The emphasis will be on the outcome of this prenatal treatment in those fetuses who are not affected with steroid 21-hydroxylase deficiency (21OHD) form of congenital adrenal hyperplasia (CAH) and are either heterozygotes or homozygote-unaffected.   Prenatal treatment of 46,XX fetuses with 21OHD (via administration of","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Congenital Adrenal Hyperplasia\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Congenital_Adrenal_Hyperplasia","name":"Congenital Adrenal Hyperplasia","kind":"Disorder","source_path":"kb/disorders/Congenital_Adrenal_Hyperplasia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Congenital_Adrenal_Hyperplasia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Congenital_Adrenal_Hyperplasia.html#dataset-dbgap-phs001317"}],"context_names":["Congenital Adrenal Hyperplasia"],"disease_names":["Congenital Adrenal Hyperplasia"],"disease_name":"Congenital Adrenal Hyperplasia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Congenital_Adrenal_Hyperplasia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Congenital_Adrenal_Hyperplasia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Congenital_Adrenal_Hyperplasia.html#dataset-dbgap-phs001317"]},{"id":"dataset:dbgap:phs001357","accession":"dbgap:phs001357","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001357","title":"The Genomic Landscape of Tuberous Sclerosis Complex (TSC)","alternate_titles":[],"description":"In this study, we characterized the genomic landscape of tuberous sclerosis complex (TSC), a rare genetic disease causing multisystem growth of benign tumors and other hamartomatous lesions. We analyzed 127 human tissues, including 111 TSC-associated samples and 16 non-TSC negative controls, using multiple genomic platforms including whole exome sequencing, targeted sequencing of known disease-causative loci ( TSC1  and  TSC2 ), mRNA sequencing, high-density SNP arrays, and DNA methylation arrays.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Tuberous Sclerosis Complex\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Tuberous_Sclerosis_Complex","name":"Tuberous Sclerosis Complex","kind":"Disorder","source_path":"kb/disorders/Tuberous_Sclerosis_Complex.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Tuberous_Sclerosis_Complex.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Tuberous_Sclerosis_Complex.html#dataset-dbgap-phs001357"}],"context_names":["Tuberous Sclerosis Complex"],"disease_names":["Tuberous Sclerosis Complex"],"disease_name":"Tuberous Sclerosis Complex","same_context_model_ids":["model:kb/disorders/Tuberous_Sclerosis_Complex.yaml:CRISPR-engineered TSC2 conditional-biallelic human cortical spheroids","model:kb/disorders/Tuberous_Sclerosis_Complex.yaml:TSC human cerebral organoids with caudal late interneuron progenitor (CLIP) over-proliferation","model:kb/disorders/Tuberous_Sclerosis_Complex.yaml:TSC patient-derived neurovascular unit (iPSC blood-brain-barrier chip)"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Tuberous_Sclerosis_Complex.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Tuberous_Sclerosis_Complex.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Tuberous_Sclerosis_Complex.html#dataset-dbgap-phs001357"]},{"id":"dataset:dbgap:phs001361","accession":"dbgap:phs001361","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001361","title":"Genetics of Age-Related Macular Degeneration in the Amish","alternate_titles":[],"description":"Identifying genetic risk loci for Age-Related Macular Degeneration is important. Most of the loci identified to date have been found through the interrogation of common variants. This study initiates the identification of rare variants in a founder population, the Amish, and will use genotyping of known risk loci and ultimately use the whole exome chip to assess the association of Age-related Macular Degeneration with coding variants.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Age-Related Macular Degeneration\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Age_Related_Macular_Degeneration","name":"Age-Related Macular Degeneration","kind":"Disorder","source_path":"kb/disorders/Age_Related_Macular_Degeneration.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Age_Related_Macular_Degeneration.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Age-Related_Macular_Degeneration.html#dataset-dbgap-phs001361"}],"context_names":["Age-Related Macular Degeneration"],"disease_names":["Age-Related Macular Degeneration"],"disease_name":"Age-Related Macular Degeneration","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Age_Related_Macular_Degeneration.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Age_Related_Macular_Degeneration.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Age-Related_Macular_Degeneration.html#dataset-dbgap-phs001361"]},{"id":"dataset:dbgap:phs001370","accession":"dbgap:phs001370","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001370","title":"Whole Exome Sequencing of Uveal Melanoma","alternate_titles":[],"description":"Uveal melanoma is a rare form of melanoma that occurs in the eye and has no effective treatment once metastatic. To further characterize the genomic events driving uveal melanoma, whole exome sequencing was performed on 61 primary tumors derived from enucleations, 3 liver metasases, and paired normal DNA. Recurrent somatic genetic alterations including point mutations, small insertions and deletions, as well as copy number variations were identified.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Uveal Melanoma\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Uveal_Melanoma","name":"Uveal Melanoma","kind":"Disorder","source_path":"kb/disorders/Uveal_Melanoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Uveal_Melanoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Uveal_Melanoma.html#dataset-dbgap-phs001370"}],"context_names":["Uveal Melanoma"],"disease_names":["Uveal Melanoma"],"disease_name":"Uveal Melanoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Uveal_Melanoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Uveal_Melanoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Uveal_Melanoma.html#dataset-dbgap-phs001370"]},{"id":"dataset:dbgap:phs001433","accession":"dbgap:phs001433","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001433","title":"Non-coding RNAs Activated in Hepatoblastoma","alternate_titles":[],"description":"Hepatoblastoma (HB) is the most common pediatric liver tumor, affecting mostly children under 3 years of age. This rare tumor represents 1% of all pediatric cancers. Genetic studies have shown that HB is characterized by high frequency mutations of the CTNNB1 gene encoding beta-catenin (around 75%) and relative genomic stability. Here we have analyzed the transcriptional profile of 21 HBs compared to matched non-tumor livers by Cap Analysis of Gene Expression (CAGE), which provides accurate and quantitative profiling of all transcripts.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Hepatoblastoma\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Hepatoblastoma","name":"Hepatoblastoma","kind":"Disorder","source_path":"kb/disorders/Hepatoblastoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatoblastoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hepatoblastoma.html#dataset-dbgap-phs001433"}],"context_names":["Hepatoblastoma"],"disease_names":["Hepatoblastoma"],"disease_name":"Hepatoblastoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hepatoblastoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatoblastoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hepatoblastoma.html#dataset-dbgap-phs001433"]},{"id":"dataset:dbgap:phs001466","accession":"dbgap:phs001466","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001466","title":"NHBLI TOPMed: Pharmacogenomics of Hydroxyurea in Sickle Cell Disease (PharmHU)","alternate_titles":[],"description":"Sickle cell disease (SCD) is characterized by the presence of sickle hemoglobin (HbS) within circulating erythrocytes resulting in hemolytic anemia, vascular occlusion, and end organ damage due to alterations in the shape and deformability of the cell membrane. The disease is inherited in an autosomal recessive pattern, and is most commonly caused by a single nucleotide substitution in the hemoglobin subunit beta (HBB) gene located on chromosome 11.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Sickle Cell Disease\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Sickle_Cell_Disease","name":"Sickle Cell Disease","kind":"Disorder","source_path":"kb/disorders/Sickle_Cell_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sickle_Cell_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Sickle_Cell_Disease.html#dataset-dbgap-phs001466"}],"context_names":["Sickle Cell Disease"],"disease_names":["Sickle Cell Disease"],"disease_name":"Sickle Cell Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Sickle_Cell_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sickle_Cell_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Sickle_Cell_Disease.html#dataset-dbgap-phs001466"]},{"id":"dataset:dbgap:phs001549","accession":"dbgap:phs001549","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001549","title":"Genome-wide Association Study and Meta-Analysis of Ewing Sarcoma","alternate_titles":[],"description":"We combined a set of 122 French Ewing sarcoma (EWS) cases from the Institut Curie, 19 EWS cases from the National Cancer Institute (NCI) Center for Cancer Research (CCR), and 29 EWS cases from the NCI Bone Disease and Injury Study. All EWS cases were confirmed by medical record review and the presence of a specific EWSR1-ETS translocation were noted when data was available. Each participant provided informed consent and each participating study was approved by the Institutional Review Boards of their study center.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Ewing Sarcoma\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Ewing_Sarcoma","name":"Ewing Sarcoma","kind":"Disorder","source_path":"kb/disorders/Ewing_Sarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ewing_Sarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#dataset-dbgap-phs001549"}],"context_names":["Ewing Sarcoma"],"disease_names":["Ewing Sarcoma"],"disease_name":"Ewing Sarcoma","same_context_model_ids":["model:kb/disorders/Ewing_Sarcoma.yaml:BARD1-variant PSaRC318 and BARD1-depleted Ewing cells","model:kb/disorders/Ewing_Sarcoma.yaml:Ewing sarcoma tumor organoid model systems","model:kb/disorders/Ewing_Sarcoma.yaml:Flow-perfusion Ewing sarcoma 3D scaffold coculture","model:kb/disorders/Ewing_Sarcoma.yaml:Human embryonic mesenchymal stem cell EWS-FLI1 transformation model","model:kb/disorders/Ewing_Sarcoma.yaml:Patient-derived Ewing sarcoma culture panel"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Ewing_Sarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ewing_Sarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#dataset-dbgap-phs001549"]},{"id":"dataset:dbgap:phs001555","accession":"dbgap:phs001555","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001555","title":"CRIM Status and Follow-up of Individuals with Pompe Disease","alternate_titles":[],"description":"Infantile-onset Pompe disease is an inherited disorder that is normally diagnosed within the first months of life. It is caused by lack of or defect in an enzyme (a special protein that carries out normal chemical reactions within the body) called acid alpha-glucosidase (GAA). GAA normally breaks down glycogen (stored sugar) in lysosomes (the part of the cell that digests food and other chemicals). Pompe disease is one of many lysosomal storage diseases (LSDs). LSDs are diseases caused by the malfunction of the lysosome or one of their digestive enzymes.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Pompe Disease\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Pompe_Disease","name":"Pompe Disease","kind":"Disorder","source_path":"kb/disorders/Pompe_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pompe_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pompe_Disease.html#dataset-dbgap-phs001555"}],"context_names":["Pompe Disease"],"disease_names":["Pompe Disease"],"disease_name":"Pompe Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Pompe_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pompe_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Pompe_Disease.html#dataset-dbgap-phs001555"]},{"id":"dataset:dbgap:phs001609","accession":"dbgap:phs001609","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001609","title":"Genetic Contributions of Lupus Nephritis in A Multi-Ethnic Cohort","alternate_titles":[],"description":"Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE) and it occurs at a much higher rate in patients that are not of European descent. The purpose of this study is to identify genetic variants contributing to the risk of LN in a multi-ethnic cohort of SLE patients. We used a comprehensive genome-wide screen and 1244 SLE patients from 5 different ethnic groups. In genome-wide gene-based and candidate SNP analyses, we found distinct genes and pathways, and established risk SNPs associated with lupus nephritis for each ethnic group.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Lupus Nephritis\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Lupus_Nephritis","name":"Lupus Nephritis","kind":"Disorder","source_path":"kb/disorders/Lupus_Nephritis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Lupus_Nephritis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Lupus_Nephritis.html#dataset-dbgap-phs001609"}],"context_names":["Lupus Nephritis"],"disease_names":["Lupus Nephritis"],"disease_name":"Lupus Nephritis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Lupus_Nephritis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Lupus_Nephritis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Lupus_Nephritis.html#dataset-dbgap-phs001609"]},{"id":"dataset:dbgap:phs001643","accession":"dbgap:phs001643","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001643","title":"Chordoma Genomics","alternate_titles":[],"description":"In this study, we performed paired tumor/normal whole exome and shallow long insert whole genome sequencing, as well as tumor RNAseq, from archival chordoma specimens collected from four patients at the Barrow Neurological Institute in Phoenix, AZ. The purpose of this analysis was to identify potential therapeutic targets. In three patients, we observed that although different DNA and RNA changes were present in each tumor, alterations fell on converging pathways.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Chordoma\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Chordoma","name":"Chordoma","kind":"Disorder","source_path":"kb/disorders/Chordoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chordoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chordoma.html#dataset-dbgap-phs001643"}],"context_names":["Chordoma"],"disease_names":["Chordoma"],"disease_name":"Chordoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chordoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chordoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chordoma.html#dataset-dbgap-phs001643"]},{"id":"dataset:dbgap:phs001672","accession":"dbgap:phs001672","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001672","title":"Million Veteran Program model-derived BED GWAS summary statistics","alternate_titles":["Million Veteran Program (MVP) rosacea genome-wide association summary statistics"],"description":"BMI-adjusted, bi-ancestry GWAS summary statistics for a machine-learning model-derived BED phenotype in the Million Veteran Program. The publication reports 77,574 participants of African ancestry and 285,138 of European ancestry and identifies loci near HFE, MCHR2, and LRP11. Access is governed by dbGaP; the phenotype is probabilistic and is not equivalent to a clinician-confirmed BED cohort.","alternate_descriptions":["Genome-wide association summary statistics for rosacea (PheCode 695.3) from the VA Million Veteran Program phenome-wide atlas, the only public rosacea GWAS with deposited full summary statistics. European-ancestry analysis of 14,815 cases and 427,372 controls; access to individual level data is governed by dbGaP. The phenotype is an EHR PheCode, not a dermatologist-confirmed cohort."],"data_types":["GWAS"],"data_type_labels":["Genome-wide association study"],"data_type_label":"Genome-wide association study","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[362712,442187],"sample_count":442187,"conditions":["Model-derived probability of binge eating disorder","BMI-adjusted African-ancestry GWAS","BMI-adjusted European-ancestry GWAS","rosacea (PheCode 695.3), European ancestry","rosacea (PheCode 695.3), African American or Afro-Caribbean ancestry","rosacea (PheCode 695.3), Hispanic or Latin American ancestry"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37550530","PMID:39024449"],"publication_contexts":[{"context_id":"disorder:Binge_Eating_Disorder","publication":"PMID:37550530"},{"context_id":"disorder:Rosacea","publication":"PMID:39024449"}],"publication":"PMID:37550530","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37550530","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:37550530","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/37550530","reference_title":"Genome-wide analysis of a model-derived binge eating disorder phenotype identifies risk loci and implicates iron metabolism.","supports":"SUPPORT","evidence_source":"COMPUTATIONAL","snippet":"We perform a genome-wide association study of individuals of African (n = 77,574) and European (n = 285,138) ancestry while controlling for body mass index to identify three independent loci near the HFE, MCHR2 and LRP11 genes and suggest APOE as a risk gene for BED.","explanation":"The publication documents the ancestry-specific sample counts, phenotype construction, and principal GWAS findings represented by this accession."}],"notes":["No evidence block: the publication is a 2,068-trait atlas whose text does not name rosacea, so nothing in it can be quoted for this record. Trait-level results are catalogued by the GWAS Catalog, which has no reference prefix in this repository, so they are recorded here as provenance. GCST90476178 (European ancestry) lists eight genome-wide significant associations: rs6866614 (IRF1/CARINH), rs12203592 (IRF4), rs12898729 (HERC2), rs5743618 (TLR1), rs10806180 (near ELOVL4), and three signals given only as positions (chr2:28627629, chr7:50327367, chr16:90024970). The IRF4 and HERC2 hits replicate the 23andMe symptom-severity loci recorded in the genetic section, and the IRF1 hit independently corroborates the Mendelian-randomization-derived IRF1 entry. The TLR1 signal is mechanistically notable given the TLR2 pathway in this entry, since TLR1 heterodimerizes with TLR2. The African-ancestry analysis (GCST90480451, 410 cases) reports nine associations dominated by pigmentation variants (rs16891982 SLC45A2, rs1805007 MC1R, rs12203592, rs12898729); with so few cases in an admixed sample these are more plausibly ancestry stratification than replication and are not curated as gene entries. The Hispanic-ancestry analysis (GCST90478792) reports no genome-wide significant hits."],"contexts":[{"id":"disorder:Binge_Eating_Disorder","name":"Binge Eating Disorder","kind":"Disorder","source_path":"kb/disorders/Binge_Eating_Disorder.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Binge_Eating_Disorder.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Binge_Eating_Disorder.html#dataset-dbgap-phs001672"},{"id":"disorder:Rosacea","name":"Rosacea","kind":"Disorder","source_path":"kb/disorders/Rosacea.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rosacea.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Rosacea.html#dataset-dbgap-phs001672"}],"context_names":["Binge Eating Disorder","Rosacea"],"disease_names":["Binge Eating Disorder","Rosacea"],"disease_name":"Binge Eating Disorder","same_context_model_ids":["model:kb/disorders/Rosacea.yaml:HaCaT keratinocytes under simulated rosacea conditions","model:kb/disorders/Rosacea.yaml:Paired lesional and non-lesional papulopustular rosacea skin explants","model:kb/disorders/Rosacea.yaml:SZ95 sebocyte and live Demodex mite co-culture"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Binge_Eating_Disorder.yaml","kb/disorders/Rosacea.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Binge_Eating_Disorder.yaml","https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rosacea.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Binge_Eating_Disorder.html#dataset-dbgap-phs001672","https://dismech.monarchinitiative.org/pages/disorders/Rosacea.html#dataset-dbgap-phs001672"]},{"id":"dataset:dbgap:phs001850","accession":"dbgap:phs001850","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001850","title":"Systemic Lupus Erythematosus Subtypes in a Multi-Ethnic Cohort","alternate_titles":[],"description":"Systemic lupus erythematosus (SLE) is a complex autoimmune disease that affects multiple organ systems and varies in severity across different populations. To examine the clinical heterogeneity of SLE, we sought to identify different lupus subtypes within our multi-ethnic cohort using a clustering approach. Additionally, with genome-wide methylation and genotype data generated for our cohort, we applied integrative methods to investigate genetic and epigenetic risk factors. This integrative and computational approach revealed molecular differences associated with phenotypic clusters.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Systemic Lupus Erythematosus\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Systemic_Lupus_Erythematosus","name":"Systemic Lupus Erythematosus","kind":"Disorder","source_path":"kb/disorders/Systemic_Lupus_Erythematosus.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Systemic_Lupus_Erythematosus.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Systemic_Lupus_Erythematosus.html#dataset-dbgap-phs001850"}],"context_names":["Systemic Lupus Erythematosus"],"disease_names":["Systemic Lupus Erythematosus"],"disease_name":"Systemic Lupus Erythematosus","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Systemic_Lupus_Erythematosus.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Systemic_Lupus_Erythematosus.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Systemic_Lupus_Erythematosus.html#dataset-dbgap-phs001850"]},{"id":"dataset:dbgap:phs001854","accession":"dbgap:phs001854","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001854","title":"Human Pilocytic Astrocytoma Single Cell RNA Sequencing","alternate_titles":[],"description":"Pilocytic astrocytoma (PA), the most common childhood brain tumor, is a low-grade glioma with a single driver BRAF rearrangement. Here, we perform scRNAseq in six PAs using methods that enabled detection of the rearrangement. When compared to higher-grade gliomas, a strikingly higher proportion of the PA cancer cells exhibit a differentiated, astrocyte-like phenotype. A smaller proportion of cells exhibit a progenitor-like phenotype with evidence of proliferation. These express a mitogen-activated protein kinase (MAPK) program that was absent from higher-grade gliomas.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Pilocytic Astrocytoma\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Pilocytic_Astrocytoma","name":"Pilocytic Astrocytoma","kind":"Disorder","source_path":"kb/disorders/Pilocytic_Astrocytoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pilocytic_Astrocytoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pilocytic_Astrocytoma.html#dataset-dbgap-phs001854"}],"context_names":["Pilocytic Astrocytoma"],"disease_names":["Pilocytic Astrocytoma"],"disease_name":"Pilocytic Astrocytoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Pilocytic_Astrocytoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pilocytic_Astrocytoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Pilocytic_Astrocytoma.html#dataset-dbgap-phs001854"]},{"id":"dataset:dbgap:phs002161","accession":"dbgap:phs002161","repository":"DBGAP","accession_url":"https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs002161","title":"Kids First: Genomic Analysis of Esophageal Atresia and Tracheoesophageal Fistulas and Associated Congenital Anomalies","alternate_titles":[],"description":"The Gabriella Miller Kids First Pediatric Research Program (Kids First) is a trans-NIH effort initiated in response to the 2014 Gabriella Miller Kids First Research Act and supported by the NIH Common Fund. This program focuses on gene discovery in pediatric cancers and structural birth defects and the development of the Gabriella Miller Kids First Pediatric Data Resource (Kids First Data Resource).        All of the WGS and phenotypic data from this study are accessible through dbGaP and  kidsfirstdrc.org , where ot","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Esophageal Atresia\"). 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from an epidemiological birth cohort","explanation":"The abstract provides the cohort size and sample type."},{"reference":"DOI:10.1111/cdev.12957","reference_url":null,"reference_title":"A Methylome-Wide Association Study of Trajectories of Oppositional Defiant Behaviors and Biological Overlap With Attention Deficit Hyperactivity Disorder","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"Methylome-wide significant associations were identified for the ODD and headstrong, but not for irritable.","explanation":"Captures the principal methylome-wide result."}],"notes":[],"contexts":[{"id":"disorder:Oppositional_Defiant_Disorder","name":"Oppositional Defiant 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<scp>callous‐unemotional</scp>\n                    traits: a systematic review and two multilevel\n                    <scp>meta‐analyses</scp>","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"treatment was associated with similar reductions in DBD symptoms for DBD+CU ( SMD  = 1.08, 95% CI = 0.45, 1.72) and DBD‐only ( SMD  = 1.01, 95% CI = 0.38, 1.64).","explanation":"Captures the primary treatment-effect comparison by CU-trait status."}]}],"findings_text":["Treatment reduced disruptive behavior symptoms in both DBD+CU and DBD-only children, but DBD+CU children had greater symptom severity."],"evidence":[{"reference":"DOI:10.1111/jcpp.13774","reference_url":null,"reference_title":"Treatment of childhood disruptive behavior disorders and\n                    <scp>callous‐unemotional</scp>\n                    traits: a systematic review and two multilevel\n                    <scp>meta‐analyses</scp>","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"Sixty studies with 9,405 participants were included","explanation":"The abstract reports the evidence base for the treatment meta-analyses."},{"reference":"DOI:10.1111/jcpp.13774","reference_url":null,"reference_title":"Treatment of childhood disruptive behavior disorders and\n                    <scp>callous‐unemotional</scp>\n                    traits: a systematic review and two multilevel\n                    <scp>meta‐analyses</scp>","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"treatment was associated with similar reductions in DBD symptoms for DBD+CU ( SMD  = 1.08, 95% CI = 0.45, 1.72) and DBD‐only ( SMD  = 1.01, 95% CI = 0.38, 1.64).","explanation":"Captures the primary treatment-effect comparison by CU-trait status."}],"notes":[],"contexts":[{"id":"disorder:Conduct_Disorder","name":"Conduct 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upregulated complement and coagulation genes","evidence":[{"reference":"PMID:38847551","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38847551","reference_title":"Single-cell RNA sequencing of cystic fibrosis liver disease explants reveals endothelial complement activation.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"we performed single-cell RNA sequencing (scRNA-seq) on four explant livers from CFLD patients to identify differential endothelial characteristics which could contribute to the disease","explanation":"First scRNA-seq characterization of endothelial involvement in CF liver disease."}]}],"findings_text":["CF liver explants contain a distinct population of sinusoidal endothelial cells with upregulated complement and coagulation genes"],"evidence":[{"reference":"PMID:38847551","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38847551","reference_title":"Single-cell RNA sequencing of cystic fibrosis liver disease explants reveals endothelial 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Spaceflight reduced ERG a-wave and b-wave amplitudes by 39% and 32% respectively, demonstrating functional photoreceptor impairment. 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retina, which may lead to photoreceptor cell damage and retinal function impairment.","explanation":"The demonstration that antioxidant therapy mitigates spaceflight retinal damage supports investigation of similar countermeasures against bisretinoid-driven oxidative stress in Stargardt disease."}]}],"findings_text":["Spaceflight causes measurable photoreceptor functional impairment (39% a-wave, 32% b-wave reduction) that is partially mitigated by antioxidant therapy, suggesting shared oxidative stress pathways with Stargardt disease."],"evidence":[{"reference":"PMID:37108526","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/37108526","reference_title":"Evidence of Spaceflight-Induced Adverse Effects on Photoreceptors and Retinal Function in the Mouse Eye.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"ERG data showed that the average amplitudes of the a- and b-wave were significantly decreased (39% and 32% by spaceflight, respectively) compared to that of habitat ground controls.","explanation":"Quantified photoreceptor functional decline after spaceflight provides a benchmark for comparing spaceflight-induced and ABCA4-related retinal dysfunction."},{"reference":"PMID:37108526","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/37108526","reference_title":"Evidence of Spaceflight-Induced Adverse Effects on Photoreceptors and Retinal Function in the Mouse Eye.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"BuOE treatment significantly decreased the level of the oxidative stress biomarker.","explanation":"Successful antioxidant countermeasure against spaceflight retinal oxidative stress suggests therapeutic overlap with oxidative RPE injury pathways in Stargardt disease."},{"reference":"PMID:37108526","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/37108526","reference_title":"Evidence of Spaceflight-Induced Adverse Effects on Photoreceptors and Retinal Function in the Mouse 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patients.","explanation":"The abstract describes the human familial WGS cohort."},{"reference":"DOI:10.3390/ijms25115758","reference_url":null,"reference_title":"Structural Variants and Implicated Processes Associated with Familial Tourette Syndrome","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"Enrichment analysis showed that identified structural variants affected synaptic vesicle endocytosis, cell leading-edge organization, and signaling for neurite outgrowth.","explanation":"Captures the principal pathway-enrichment finding from the dataset."}],"notes":[],"contexts":[{"id":"disorder:Tourette_Syndrome","name":"Tourette 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pathophysiology of AN, such as processes of adaptation to starvation.","explanation":"The authors explicitly use associative language and interpret the finding as adaptation to starvation."}]}],"findings_text":["Multiple endocrine and metabolic biomarkers differ between AN and non-AN groups, consistent with starvation adaptation but not diagnostic specificity."],"evidence":[{"reference":"DOI:10.3390/nu16132095","reference_url":null,"reference_title":"Peripheral Biomarkers of Anorexia Nervosa: A Meta-Analysis","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"We conducted two-level random-effects meta-analyses to examine the difference between AN and comparison groups across 52 distinct biomarkers","explanation":"The abstract describes the dataset scope and analysis design."},{"reference":"DOI:10.3390/nu16132095","reference_url":null,"reference_title":"Peripheral Biomarkers of Anorexia Nervosa: A 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Multiple mutation signatures testify to the cocktail of carcinogens in tobacco smoke and their proclivities for particular bases and surrounding sequence context.","alternate_descriptions":[],"data_types":["WGS"],"data_type_labels":["Whole genome sequencing"],"data_type_label":"Whole genome sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Small Cell Lung Cancer\"); description-level mentions were not accepted. EGA study_type: Whole Genome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Small_Cell_Lung_Cancer","name":"Small Cell Lung Cancer","kind":"Disorder","source_path":"kb/disorders/Small_Cell_Lung_Cancer.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Small_Cell_Lung_Cancer.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Small_Cell_Lung_Cancer.html#dataset-ega-egas00000000051"}],"context_names":["Small Cell Lung Cancer"],"disease_names":["Small Cell Lung Cancer"],"disease_name":"Small Cell Lung Cancer","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Small_Cell_Lung_Cancer.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Small_Cell_Lung_Cancer.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Small_Cell_Lung_Cancer.html#dataset-ega-egas00000000051"]},{"id":"dataset:ega:egas00000000060","accession":"ega:EGAS00000000060","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00000000060","title":"A genome-wide meta analysis on stroke and ischemic stroke within four populations","alternate_titles":[],"description":"In this analysis a genome-wide meta-analysis was performed on all stroke and ischemic stroke.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Ischemic Stroke\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Ischemic_Stroke","name":"Ischemic Stroke","kind":"Disorder","source_path":"kb/disorders/Ischemic_Stroke.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ischemic_Stroke.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Ischemic_Stroke.html#dataset-ega-egas00000000060"}],"context_names":["Ischemic Stroke"],"disease_names":["Ischemic Stroke"],"disease_name":"Ischemic Stroke","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Ischemic_Stroke.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ischemic_Stroke.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Ischemic_Stroke.html#dataset-ega-egas00000000060"]},{"id":"dataset:ega:egas00000000075","accession":"ega:EGAS00000000075","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00000000075","title":"ARID1A Mutations in Endometriosis-Associated Ovarian Carcinomas","alternate_titles":[],"description":"We have sequenced the whole transcriptomes of 18 ovarian clear-cell carcinomas and 1 ovarian clear-cell carcinoma cell line and found somatic mutations in ARID1A (the AT-rich interactive domain 1A [SWI-like] gene) in 6 of the samples. ARID1A encodes BAF250a, a key component of the SWI–SNF chromatin remodeling complex. We sequenced ARID1A in an additional 210 ovarian carcinomas and a second ovarian clear-cell carcinoma cell line and measured BAF250a expression by means of immunohistochemical analysis in an additional 455 ovarian carcinomas","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Endometriosis\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Endometriosis","name":"Endometriosis","kind":"Disorder","source_path":"kb/disorders/Endometriosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Endometriosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Endometriosis.html#dataset-ega-egas00000000075"}],"context_names":["Endometriosis"],"disease_names":["Endometriosis"],"disease_name":"Endometriosis","same_context_model_ids":["model:kb/disorders/Endometriosis.yaml:Droplet-based microfluidic protease-activity profiling platform (PrAMA; MIT Griffith/Han)"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Endometriosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Endometriosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Endometriosis.html#dataset-ega-egas00000000075"]},{"id":"dataset:ega:egas00000000101","accession":"ega:EGAS00000000101","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00000000101","title":"The Genetic Analysis of multiple sclerosis","alternate_titles":[],"description":"We created these data in order to identify genetic variants associated with increased susceptibility to multiple sclerosis. 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In our analysis we also used control data from the WTCCC2 common UK controls and from other published studies.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Multiple Sclerosis\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Multiple_Sclerosis","name":"Multiple Sclerosis","kind":"Disorder","source_path":"kb/disorders/Multiple_Sclerosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Multiple_Sclerosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Multiple_Sclerosis.html#dataset-ega-egas00000000101"}],"context_names":["Multiple Sclerosis"],"disease_names":["Multiple Sclerosis"],"disease_name":"Multiple Sclerosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Multiple_Sclerosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Multiple_Sclerosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Multiple_Sclerosis.html#dataset-ega-egas00000000101"]},{"id":"dataset:ega:egas00000000104","accession":"ega:EGAS00000000104","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00000000104","title":"Genomewide association studies in ankylosing spondylitis","alternate_titles":[],"description":"The aim of this study was to identify genes associated with ankylosing spondylitis susceptibility in British and Australian individuals of European descent.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Ankylosing Spondylitis\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Ankylosing_Spondylitis","name":"Ankylosing Spondylitis","kind":"Disorder","source_path":"kb/disorders/Ankylosing_Spondylitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ankylosing_Spondylitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Ankylosing_Spondylitis.html#dataset-ega-egas00000000104"}],"context_names":["Ankylosing Spondylitis"],"disease_names":["Ankylosing Spondylitis"],"disease_name":"Ankylosing Spondylitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Ankylosing_Spondylitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ankylosing_Spondylitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Ankylosing_Spondylitis.html#dataset-ega-egas00000000104"]},{"id":"dataset:ega:egas00000000105","accession":"ega:EGAS00000000105","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00000000105","title":"Copy number analysis of Diamond-Blackfan Anemia (DBA) using SNP array","alternate_titles":[],"description":"Diamond–Blackfan anemia (DBA), is a rare congenital anemia that usually presents in infancy. About fifty percent of DBA patients possess mutations in ribosomal protains (RPs). In this study, we performed genomic copy number analysis using SNP arrays for 27 Japanese DBA patients to detect genomic copy number lesions of the RP genes' loci.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Diamond-Blackfan Anemia\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Diamond-Blackfan_Anemia","name":"Diamond-Blackfan Anemia","kind":"Disorder","source_path":"kb/disorders/Diamond-Blackfan_Anemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Diamond-Blackfan_Anemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Diamond-Blackfan_Anemia.html#dataset-ega-egas00000000105"}],"context_names":["Diamond-Blackfan Anemia"],"disease_names":["Diamond-Blackfan Anemia"],"disease_name":"Diamond-Blackfan Anemia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Diamond-Blackfan_Anemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Diamond-Blackfan_Anemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Diamond-Blackfan_Anemia.html#dataset-ega-egas00000000105"]},{"id":"dataset:ega:egas00000000118","accession":"ega:EGAS00000000118","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00000000118","title":"WTCCC2 Schizophrenia study","alternate_titles":[],"description":"A WTCCC2 project genome-wide case-control association study for schizophrenia (SP) in individuals from Ireland.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Schizophrenia\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Schizophrenia","name":"Schizophrenia","kind":"Disorder","source_path":"kb/disorders/Schizophrenia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Schizophrenia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Schizophrenia.html#dataset-ega-egas00000000118"}],"context_names":["Schizophrenia"],"disease_names":["Schizophrenia"],"disease_name":"Schizophrenia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Schizophrenia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Schizophrenia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Schizophrenia.html#dataset-ega-egas00000000118"]},{"id":"dataset:ega:egas00000000129","accession":"ega:EGAS00000000129","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00000000129","title":"The complex SNP and CNV genetic architecture of the increased risk of  congenital heart defects in Down syndrome","alternate_titles":[],"description":"Here we aimed to contribute to the description of the genetic architecture of Congenital heart defect (CHD) in Down syndrome (DS), and report the results of a genome-wide association study using samples from DS individuals with and without CHD. CHD is a common developmental defect of DS occurring in 40% of cases. This case-control GWAS includes 187 DS with CHD as cases, and 151 DS without CHD as controls.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Down syndrome\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Down_syndrome","name":"Down_syndrome","kind":"Disorder","source_path":"kb/disorders/Down_syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Down_syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Down_syndrome.html#dataset-ega-egas00000000129"}],"context_names":["Down_syndrome"],"disease_names":["Down_syndrome"],"disease_name":"Down_syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Down_syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Down_syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Down_syndrome.html#dataset-ega-egas00000000129"]},{"id":"dataset:ega:egas00001000085","accession":"ega:EGAS00001000085","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000085","title":"Linking genes, genomic instability and molecular subgroups in medulloblastoma","alternate_titles":[],"description":"Brain tumors are the second most common pediatric cancer and carry the highest mortality rates in this age group. Medulloblastoma is the most frequent malignant brain tumor of childhood. Recent studies indicate that medulloblastoma comprises at least four sub-entities (SHH-signaling, WNT-signaling, Group-C, Group-D) that differ in molecular alterations, cell of origin, clinicopathological features and outcome. Further characterization of the entire spectrum of genomic alterations underlying the formation of these distinct groups is urgently needed to identify diagnostic and prognostic biomarkers for clinical management and uncover novel therapeutic targets.","alternate_descriptions":[],"data_types":["WGS"],"data_type_labels":["Whole genome sequencing"],"data_type_label":"Whole genome sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:22265402"],"publication_contexts":[{"context_id":"disorder:Medulloblastoma","publication":"PMID:22265402"}],"publication":"PMID:22265402","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/22265402","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Medulloblastoma\"); description-level mentions were not accepted. EGA study_type: Whole Genome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Medulloblastoma","name":"Medulloblastoma","kind":"Disorder","source_path":"kb/disorders/Medulloblastoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Medulloblastoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Medulloblastoma.html#dataset-ega-egas00001000085"}],"context_names":["Medulloblastoma"],"disease_names":["Medulloblastoma"],"disease_name":"Medulloblastoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Medulloblastoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Medulloblastoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Medulloblastoma.html#dataset-ega-egas00001000085"]},{"id":"dataset:ega:egas00001000096","accession":"ega:EGAS00001000096","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000096","title":"Identification of improved IL28B SNPs and haplotypes for prediction of drug response in treatment of hepatitis C using massively parallel sequencing in a cross-sectional European cohort","alternate_titles":[],"description":"The hepatitis C virus infects nearly 3% of the World’s population, causing severe liver disease in many. Standard of care therapy is currently pegylated interferon alpha and ribavirin (PegIFN/R), which is effective in less than half of those infected with the most common viral genotype. Two IL28B SNPs, rs8099917 and rs12979860, predict response to (PegIFN/R) therapy in treatment of hepatitis C virus infection. These SNPs were identified in genome wide analyses using Illumina genotyping chips. In people of European ancestry, there are 6 common (>1%) haplotypes for IL28B, one tagged by rs8099917 minor allele, four tagged by rs12979860.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Hepatitis C\"); description-level mentions were not accepted. EGA study_type: Resequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Hepatitis_C","name":"Hepatitis C","kind":"Disorder","source_path":"kb/disorders/Hepatitis_C.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatitis_C.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hepatitis_C.html#dataset-ega-egas00001000096"}],"context_names":["Hepatitis C"],"disease_names":["Hepatitis C"],"disease_name":"Hepatitis C","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hepatitis_C.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatitis_C.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hepatitis_C.html#dataset-ega-egas00001000096"]},{"id":"dataset:ega:egas00001000152","accession":"ega:EGAS00001000152","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000152","title":"Full genome sequencing of a monozygotic twin discordant for schizophrenia","alternate_titles":[],"description":"We sequenced the genomes from a monozygotic twin discordant for schizophrenia and a tumor-normal pair of an ovarian cancer patient. Using whole-genome twin data to discriminate between correctly identified single nucleotide variants (SNVs) and errors a strategy for the accurate detection of SNVs was developed. By applying stringent sequencing quality measures, excluding error-prone regions and selecting SNVs identified by different mapping and variation calling algorithms, error rates were ~37-fold reduced. This enabled us to identify the first discordant SNVs in monozygotic twins using whole-genome sequencing.","alternate_descriptions":[],"data_types":["WGS"],"data_type_labels":["Whole genome sequencing"],"data_type_label":"Whole genome sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Schizophrenia\"); description-level mentions were not accepted. EGA study_type: Whole Genome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Schizophrenia","name":"Schizophrenia","kind":"Disorder","source_path":"kb/disorders/Schizophrenia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Schizophrenia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Schizophrenia.html#dataset-ega-egas00001000152"}],"context_names":["Schizophrenia"],"disease_names":["Schizophrenia"],"disease_name":"Schizophrenia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Schizophrenia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Schizophrenia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Schizophrenia.html#dataset-ega-egas00001000152"]},{"id":"dataset:ega:egas00001000217","accession":"ega:EGAS00001000217","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000217","title":"Exome-sequencing identifies new oncogenes and tumor suppressor genes recurrently altered in hepatocellular carcinoma","alternate_titles":[],"description":"Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. High-resolution copy number analysis of 125 tumors of which 24 were subjected to whole-exome sequencing identified 135 homozygous deletions and 994 somatic gene mutations with predicted functional consequences. We identified new recurrent alterations in 4 genes (ARID1A, RPS6KA3, NFE2L2 and IRF2) not previously described in HCC. Functional analyses demonstrated tumor suppressor properties for IRF2 whose inactivation, exclusively found in hepatitis B virus related tumors, leads to impaired TP53 function.","alternate_descriptions":[],"data_types":["WES"],"data_type_labels":["Whole exome sequencing"],"data_type_label":"Whole exome sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:22561517"],"publication_contexts":[{"context_id":"disorder:Hepatocellular_Carcinoma","publication":"PMID:22561517"}],"publication":"PMID:22561517","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/22561517","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Hepatocellular Carcinoma\"); description-level mentions were not accepted. EGA study_type: Exome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Hepatocellular_Carcinoma","name":"Hepatocellular Carcinoma","kind":"Disorder","source_path":"kb/disorders/Hepatocellular_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatocellular_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hepatocellular_Carcinoma.html#dataset-ega-egas00001000217"}],"context_names":["Hepatocellular Carcinoma"],"disease_names":["Hepatocellular Carcinoma"],"disease_name":"Hepatocellular Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hepatocellular_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatocellular_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hepatocellular_Carcinoma.html#dataset-ega-egas00001000217"]},{"id":"dataset:ega:egas00001000246","accession":"ega:EGAS00001000246","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000246","title":"Genetic landscape of pediatric Infant Acute Lymphoblastic leukemia","alternate_titles":[],"description":"We performed whole genome sequencing of tumor and normal DNA samples obtained from 22 infant ALL cases with MLL rearrangements. In addition, we sequenced 2 paired diagnostic-relapse samples. Using complementary pipelines, somatically acquired genetic changes were analyzed, including single nucleotide variations (SNVs), insertion/deletions, structural variations and copy number variations in the cancer genomes. In addition, exome sequencing was performed on paired diagnostic and normal DNA samples obtained from 20 cases of non-infant MLL rearranged leukemias and somatic mutations in the coding regions were identified.","alternate_descriptions":[],"data_types":["WGS"],"data_type_labels":["Whole genome sequencing"],"data_type_label":"Whole genome sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Acute Lymphoblastic Leukemia\"); description-level mentions were not accepted. EGA study_type: Whole Genome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Acute_Lymphoblastic_Leukemia","name":"Acute Lymphoblastic Leukemia","kind":"Disorder","source_path":"kb/disorders/Acute_Lymphoblastic_Leukemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Acute_Lymphoblastic_Leukemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Acute_Lymphoblastic_Leukemia.html#dataset-ega-egas00001000246"}],"context_names":["Acute Lymphoblastic Leukemia"],"disease_names":["Acute Lymphoblastic Leukemia"],"disease_name":"Acute Lymphoblastic Leukemia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Acute_Lymphoblastic_Leukemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Acute_Lymphoblastic_Leukemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Acute_Lymphoblastic_Leukemia.html#dataset-ega-egas00001000246"]},{"id":"dataset:ega:egas00001000253","accession":"ega:EGAS00001000253","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000253","title":"Whole genome sequencing of pediatric BCR-ABL1 positive acute lymphoblastic leukemia","alternate_titles":[],"description":"We performed whole-genome sequencing of 18 paired tumor/normal BCR-ABL1+ leukemia genomes and analyzed single nucleotide variations (SNVs), insertion/deletions, structural variations and copy number variations in the tumor and normal genomes","alternate_descriptions":[],"data_types":["WGS"],"data_type_labels":["Whole genome sequencing"],"data_type_label":"Whole genome sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Acute Lymphoblastic Leukemia\"); description-level mentions were not accepted. EGA study_type: Whole Genome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Acute_Lymphoblastic_Leukemia","name":"Acute Lymphoblastic Leukemia","kind":"Disorder","source_path":"kb/disorders/Acute_Lymphoblastic_Leukemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Acute_Lymphoblastic_Leukemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Acute_Lymphoblastic_Leukemia.html#dataset-ega-egas00001000253"}],"context_names":["Acute Lymphoblastic Leukemia"],"disease_names":["Acute Lymphoblastic Leukemia"],"disease_name":"Acute Lymphoblastic Leukemia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Acute_Lymphoblastic_Leukemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Acute_Lymphoblastic_Leukemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Acute_Lymphoblastic_Leukemia.html#dataset-ega-egas00001000253"]},{"id":"dataset:ega:egas00001000273","accession":"ega:EGAS00001000273","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000273","title":"Stratifying and Targeting Pediatric Medulloblastoma through Genomics","alternate_titles":[],"description":"In this project, genomic analyses of pediatric medulloblastoma samples, obtained through the international medulloblastoma consortium, will be performed. RNA and miRNA expression profiles of 1000 samples, representing all four subgroups (Wnt, Shh, Group C, and D), will be studied to identify novel subtypes within each subgroup. The resulting subtype-specific expression profiles will support the development of reliable and robust biomarkers to more accurately and reliably classify medulloblastomas for treatment in clinical trials. For that purpose, two assays will be developed: an antibody-based immunohistochemical assay and an orthogonal nucleic acid-based hybridization assay.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:22832581"],"publication_contexts":[{"context_id":"disorder:Medulloblastoma","publication":"PMID:22832581"}],"publication":"PMID:22832581","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/22832581","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Medulloblastoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Medulloblastoma","name":"Medulloblastoma","kind":"Disorder","source_path":"kb/disorders/Medulloblastoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Medulloblastoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Medulloblastoma.html#dataset-ega-egas00001000273"}],"context_names":["Medulloblastoma"],"disease_names":["Medulloblastoma"],"disease_name":"Medulloblastoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Medulloblastoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Medulloblastoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Medulloblastoma.html#dataset-ega-egas00001000273"]},{"id":"dataset:ega:egas00001000296","accession":"ega:EGAS00001000296","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000296","title":"Exome sequencing identifies mutation of the ribosome in T-cell acute lymphoblastic leukemia","alternate_titles":[],"description":"Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy and responds well to therapy in children, but not in adults. We used exome sequencing of 67 T-cell ALL (T- ALL) samples to gain insight in the mutational spectrum and age related differences of these leukemias. We detected protein-altering mutations in 508 genes, with an average of 8.2 mutations in pediatric and 21.0 in adult T-ALL. Based on stringent filtering, we predict 15 of these genes to be drivers, including 7 genes that were not previously implicated in T-ALL.","alternate_descriptions":[],"data_types":["WES"],"data_type_labels":["Whole exome sequencing"],"data_type_label":"Whole exome sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Acute Lymphoblastic Leukemia\"); description-level mentions were not accepted. EGA study_type: Exome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Acute_Lymphoblastic_Leukemia","name":"Acute Lymphoblastic Leukemia","kind":"Disorder","source_path":"kb/disorders/Acute_Lymphoblastic_Leukemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Acute_Lymphoblastic_Leukemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Acute_Lymphoblastic_Leukemia.html#dataset-ega-egas00001000296"}],"context_names":["Acute Lymphoblastic Leukemia"],"disease_names":["Acute Lymphoblastic Leukemia"],"disease_name":"Acute Lymphoblastic Leukemia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Acute_Lymphoblastic_Leukemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Acute_Lymphoblastic_Leukemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Acute_Lymphoblastic_Leukemia.html#dataset-ega-egas00001000296"]},{"id":"dataset:ega:egas00001000299","accession":"ega:EGAS00001000299","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000299","title":"Integrative analysis of small cell lung cancer","alternate_titles":[],"description":"Small-cell lung cancer (SCLC) is an aggressive lung tumor subtype. We conducted integrated analysis of genome sequencing, transcriptome, and copy number analysis and found an extremely high mutation rate of 7.4±1 protein-changing mutations per million basepairs. Evidence for inactivation of TP53 and RB1 was found in all sequenced cases. Furthermore, we identified recurrent mutations in CREBBP, EP300, and MLL, observed mutations in PTEN, in SLIT2, and EPHA7, as well as focal amplifications of the FGFR1 locus.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:22941188"],"publication_contexts":[{"context_id":"disorder:Small_Cell_Lung_Cancer","publication":"PMID:22941188"}],"publication":"PMID:22941188","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/22941188","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Small Cell Lung Cancer\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Small_Cell_Lung_Cancer","name":"Small Cell Lung Cancer","kind":"Disorder","source_path":"kb/disorders/Small_Cell_Lung_Cancer.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Small_Cell_Lung_Cancer.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Small_Cell_Lung_Cancer.html#dataset-ega-egas00001000299"}],"context_names":["Small Cell Lung Cancer"],"disease_names":["Small Cell Lung Cancer"],"disease_name":"Small Cell Lung Cancer","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Small_Cell_Lung_Cancer.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Small_Cell_Lung_Cancer.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Small_Cell_Lung_Cancer.html#dataset-ega-egas00001000299"]},{"id":"dataset:ega:egas00001000325","accession":"ega:EGAS00001000325","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000325","title":"Whole genome sequencing of hepatocellular carcinoma tumors and their matched noncancerous liver tissues and the background germline","alternate_titles":[],"description":"We performed whole-genome sequencing on multifocal hepatocellular carcinoma tumors and their matched noncancerous liver tissues and the background germline. We found that the noncancerous liver tissues presented varying degrees of genomic alterations that were associated with the background liver diseases. Most of the genomic alterations in the metastatic tumors were inherited from the primary tumor and a small number developed de novo. Few genomic alterations were shared between the multicentric tumors with the exception of the alterations that also existed in the noncancerous liver tissue.","alternate_descriptions":[],"data_types":["WGS"],"data_type_labels":["Whole genome sequencing"],"data_type_label":"Whole genome sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Hepatocellular Carcinoma\"); description-level mentions were not accepted. EGA study_type: Whole Genome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Hepatocellular_Carcinoma","name":"Hepatocellular Carcinoma","kind":"Disorder","source_path":"kb/disorders/Hepatocellular_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatocellular_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hepatocellular_Carcinoma.html#dataset-ega-egas00001000325"}],"context_names":["Hepatocellular Carcinoma"],"disease_names":["Hepatocellular Carcinoma"],"disease_name":"Hepatocellular Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hepatocellular_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatocellular_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hepatocellular_Carcinoma.html#dataset-ega-egas00001000325"]},{"id":"dataset:ega:egas00001000334","accession":"ega:EGAS00001000334","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000334","title":"Genentech Small Cell Lung Cancer (SCLC) Screen","alternate_titles":[],"description":"Exome capture, RNA-Seq, whole genome sequencing of set of Small Cell Lung Cancer samples.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:22941189"],"publication_contexts":[{"context_id":"disorder:Small_Cell_Lung_Cancer","publication":"PMID:22941189"}],"publication":"PMID:22941189","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/22941189","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Small Cell Lung Cancer\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Small_Cell_Lung_Cancer","name":"Small Cell Lung Cancer","kind":"Disorder","source_path":"kb/disorders/Small_Cell_Lung_Cancer.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Small_Cell_Lung_Cancer.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Small_Cell_Lung_Cancer.html#dataset-ega-egas00001000334"}],"context_names":["Small Cell Lung Cancer"],"disease_names":["Small Cell Lung Cancer"],"disease_name":"Small Cell Lung Cancer","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Small_Cell_Lung_Cancer.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Small_Cell_Lung_Cancer.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Small_Cell_Lung_Cancer.html#dataset-ega-egas00001000334"]},{"id":"dataset:ega:egas00001000346","accession":"ega:EGAS00001000346","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000346","title":"Genetic landscape of pediatric Retinoblastoma","alternate_titles":[],"description":"Retinoblastoma is a pediatric cancer of the developing retina. All retinoblastomas are believed to initiate with biallelic inactivation of the RB1 gene. To identify subsequent genetic lesions in retinoblastoma, we performed whole genome sequencing of tumor and normal DNA of 4 children with retinoblastoma and one matched orthotopic xenograft. Both alleles of RB1 were inactivated in the tumor samples. 3 of the patients had sporadic retinoblastoma and one patient had inherited retinoblastoma. Overall, there were few single nucleotide changes in coding regions of the genome and some of the tumors had few chromosomal lesions.","alternate_descriptions":[],"data_types":["WGS"],"data_type_labels":["Whole genome sequencing"],"data_type_label":"Whole genome sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:22237022"],"publication_contexts":[{"context_id":"disorder:Retinoblastoma","publication":"PMID:22237022"}],"publication":"PMID:22237022","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/22237022","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Retinoblastoma\"); description-level mentions were not accepted. EGA study_type: Whole Genome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Retinoblastoma","name":"Retinoblastoma","kind":"Disorder","source_path":"kb/disorders/Retinoblastoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Retinoblastoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Retinoblastoma.html#dataset-ega-egas00001000346"}],"context_names":["Retinoblastoma"],"disease_names":["Retinoblastoma"],"disease_name":"Retinoblastoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Retinoblastoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Retinoblastoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Retinoblastoma.html#dataset-ega-egas00001000346"]},{"id":"dataset:ega:egas00001000347","accession":"ega:EGAS00001000347","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000347","title":"Genetic landscape of pediatric Medulloblastoma","alternate_titles":[],"description":"Medulloblastoma is a heterogenous disease made up of at least four distinct subtypes of disease which appear to exploit and disrupt naturally occurring developmental pathways of cellular growth and hindbrain development. To better understand the driver mutations of this disease, we performed whole genome sequencing of 37 medulloblastomas and the corresponding normal DNA of the 37 affected children treated at St. Jude Children's Research Hospital. We have found several novel mutations which appear subtype specific. These mutations were checked for frequency in a separate tumor cohort of 56 children with medulloblastoma, also treated on the St.","alternate_descriptions":[],"data_types":["WGS"],"data_type_labels":["Whole genome sequencing"],"data_type_label":"Whole genome sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Medulloblastoma\"); description-level mentions were not accepted. EGA study_type: Whole Genome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Medulloblastoma","name":"Medulloblastoma","kind":"Disorder","source_path":"kb/disorders/Medulloblastoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Medulloblastoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Medulloblastoma.html#dataset-ega-egas00001000347"}],"context_names":["Medulloblastoma"],"disease_names":["Medulloblastoma"],"disease_name":"Medulloblastoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Medulloblastoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Medulloblastoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Medulloblastoma.html#dataset-ega-egas00001000347"]},{"id":"dataset:ega:egas00001000372","accession":"ega:EGAS00001000372","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000372","title":"Poly(A) RNA sequencing of hepatocellular carcinoma tumors and their matched noncancerous liver tissues","alternate_titles":[],"description":"We performed poly(A) RNA sequencing on multiple hepatocellular carcinoma tumors and their matched noncancerous liver tissues.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Hepatocellular Carcinoma\"); description-level mentions were not accepted. EGA study_type: Transcriptome Analysis. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Hepatocellular_Carcinoma","name":"Hepatocellular Carcinoma","kind":"Disorder","source_path":"kb/disorders/Hepatocellular_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatocellular_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hepatocellular_Carcinoma.html#dataset-ega-egas00001000372"}],"context_names":["Hepatocellular Carcinoma"],"disease_names":["Hepatocellular Carcinoma"],"disease_name":"Hepatocellular Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hepatocellular_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatocellular_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hepatocellular_Carcinoma.html#dataset-ega-egas00001000372"]},{"id":"dataset:ega:egas00001000375","accession":"ega:EGAS00001000375","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000375","title":"Exome sequencing of paired tumor/normal DNA samples from the eight intrahepatic cholangiocarcinoma patients","alternate_titles":[],"description":"Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver malignancy after hepatocellular carcinoma, with increasing incidence worldwide. To gain new insight into the genetic basis of ICC, we performed whole-exome sequencing of paired tumor/normal DNA samples from the 8 ICC patients. The patients underwent surgical resection at the Liver Cancer Institute, Zhongshan Hospital of Fudan University. The study was approved by the Zhongshan Hospital Ethics Committee, and informed consent was obtained from each patients under Institutional Review Board protocols. Tumor tissue was analyzed by frozen section to assess neoplastic cellularity (above 80%).","alternate_descriptions":[],"data_types":["WES"],"data_type_labels":["Whole exome sequencing"],"data_type_label":"Whole exome sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Cholangiocarcinoma\"); description-level mentions were not accepted. EGA study_type: Exome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Cholangiocarcinoma","name":"Cholangiocarcinoma","kind":"Disorder","source_path":"kb/disorders/Cholangiocarcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cholangiocarcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cholangiocarcinoma.html#dataset-ega-egas00001000375"}],"context_names":["Cholangiocarcinoma"],"disease_names":["Cholangiocarcinoma"],"disease_name":"Cholangiocarcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cholangiocarcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cholangiocarcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cholangiocarcinoma.html#dataset-ega-egas00001000375"]},{"id":"dataset:ega:egas00001000399","accession":"ega:EGAS00001000399","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000399","title":"Integrated genomic analysis identifies recurrent mutations and evolution patterns driving the initiation and progression of follicular lymphoma.","alternate_titles":[],"description":"follicular lymphoma (FL), the most common indolent non-Hodgkin’s lymphoma, remains incurable. A well-recognized complication of FL is its transformation to a diffuse large B-cell lymphoma (DLBCL)-morphology in a subset of patients, for which the clinical outcomes are poor. Recent genetic profiling and single case studies of donor-derived FL following stem cell transplantation had alluded to the putative existence of a ‘long lived’ tumor-initiating progenitor cell compartment from which successive disease events occurred.","alternate_descriptions":[],"data_types":["WGS"],"data_type_labels":["Whole genome sequencing"],"data_type_label":"Whole genome sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Follicular Lymphoma\"); description-level mentions were not accepted. EGA study_type: Whole Genome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Follicular_Lymphoma","name":"Follicular Lymphoma","kind":"Disorder","source_path":"kb/disorders/Follicular_Lymphoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Follicular_Lymphoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Follicular_Lymphoma.html#dataset-ega-egas00001000399"}],"context_names":["Follicular Lymphoma"],"disease_names":["Follicular Lymphoma"],"disease_name":"Follicular Lymphoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Follicular_Lymphoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Follicular_Lymphoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Follicular_Lymphoma.html#dataset-ega-egas00001000399"]},{"id":"dataset:ega:egas00001000416","accession":"ega:EGAS00001000416","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000416","title":"Preeclampsia InterPregGen Consortium: Whole Genome Sequencing of 100 unrelated Uzbeks (DNA samples from the Institute of Immunology, Uzbek Academy of Sciences, Tashkent, Uzbekistan; Republic Specialized Scientific Practical Medical Centre of Obstetrics and Gynecology, Tashkent, Uzbekistan)","alternate_titles":[],"description":"Preeclampsia (PE) is a syndrome affecting pregnant mothers and fetus/babies characterised by hypertension and proteinuria, and is a leading cause of maternal and fetal death and of premature births worldwide. The InterPregGen Consortium was funded by a European Framework 7 (FP7) grant and grew out of the WTCCC3 GWAS comparing ~2000 UK PE mothers with ~6000 common UK controls.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:33239696"],"publication_contexts":[{"context_id":"disorder:Preeclampsia","publication":"PMID:33239696"}],"publication":"PMID:33239696","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/33239696","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Preeclampsia\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Preeclampsia","name":"Preeclampsia","kind":"Disorder","source_path":"kb/disorders/Preeclampsia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Preeclampsia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Preeclampsia.html#dataset-ega-egas00001000416"}],"context_names":["Preeclampsia"],"disease_names":["Preeclampsia"],"disease_name":"Preeclampsia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Preeclampsia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Preeclampsia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Preeclampsia.html#dataset-ega-egas00001000416"]},{"id":"dataset:ega:egas00001000417","accession":"ega:EGAS00001000417","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000417","title":"Preeclampsia InterPregGen Consortium: Whole Genome Sequencing of 100 unrelated Kazakhs (DNA samples from the Scientific Center of Obstetrics, Gynecology and Perinatology, Almaty, Kazakhstan; Gulnara Svyatova, Principal Investigator","alternate_titles":[],"description":"Preeclampsia (PE) is a syndrome affecting pregnant mothers and fetus/babies characterised by hypertension and proteinuria, and is a leading cause of maternal and fetal death and of premature births worldwide. The InterPregGen Consortium was funded by a European Framework 7 (FP7) grant and grew out of the WTCCC3 GWAS comparing ~2000 UK PE mothers with ~6000 common UK controls.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:33239696"],"publication_contexts":[{"context_id":"disorder:Preeclampsia","publication":"PMID:33239696"}],"publication":"PMID:33239696","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/33239696","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Preeclampsia\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Preeclampsia","name":"Preeclampsia","kind":"Disorder","source_path":"kb/disorders/Preeclampsia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Preeclampsia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Preeclampsia.html#dataset-ega-egas00001000417"}],"context_names":["Preeclampsia"],"disease_names":["Preeclampsia"],"disease_name":"Preeclampsia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Preeclampsia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Preeclampsia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Preeclampsia.html#dataset-ega-egas00001000417"]},{"id":"dataset:ega:egas00001000451","accession":"ega:EGAS00001000451","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000451","title":"Plasma-Seq of patients with metastatic prostate cancer","alternate_titles":[],"description":"Study 1 In this study we analysed patients with metastatic prostate cancer to scan their tumor genomes noninvasively in plasma DNA. We wanted to make whole-genome analysis from plasma DNA amenable to clinical routine applications and developed an approach based on a benchtop high-throughput platform, i.e. Illuminas MiSeq instrument. We performed whole-genome sequencing from plasma at a shallow sequencing depth to establish a genome-wide copy number profile of the tumor at low costs within 2 days. The genome-wide profiling in the plasma of our patients revealed multiple copy number aberrations including those previously reported in prostate tumors, such as losses in 8p and gains in 8q.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:23561577"],"publication_contexts":[{"context_id":"disorder:Prostate_Adenocarcinoma","publication":"PMID:23561577"}],"publication":"PMID:23561577","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/23561577","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Metastatic Prostate Cancer\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Prostate_Adenocarcinoma","name":"Prostate Adenocarcinoma","kind":"Disorder","source_path":"kb/disorders/Prostate_Adenocarcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Prostate_Adenocarcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Prostate_Adenocarcinoma.html#dataset-ega-egas00001000451"}],"context_names":["Prostate Adenocarcinoma"],"disease_names":["Prostate Adenocarcinoma"],"disease_name":"Prostate Adenocarcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Prostate_Adenocarcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Prostate_Adenocarcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Prostate_Adenocarcinoma.html#dataset-ega-egas00001000451"]},{"id":"dataset:ega:egas00001000453","accession":"ega:EGAS00001000453","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000453","title":"Identification of mutations and structural rearrangements in plasma DNA form metastatic prostate cancer patients","alternate_titles":[],"description":"In this study we analysed patients with metastatic prostate cancer to scan their tumor genomes noninvasively in plasma DNA. 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EGA study_type: Resequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Prostate_Adenocarcinoma","name":"Prostate Adenocarcinoma","kind":"Disorder","source_path":"kb/disorders/Prostate_Adenocarcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Prostate_Adenocarcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Prostate_Adenocarcinoma.html#dataset-ega-egas00001000453"}],"context_names":["Prostate Adenocarcinoma"],"disease_names":["Prostate Adenocarcinoma"],"disease_name":"Prostate Adenocarcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Prostate_Adenocarcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Prostate_Adenocarcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Prostate_Adenocarcinoma.html#dataset-ega-egas00001000453"]},{"id":"dataset:ega:egas00001000505","accession":"ega:EGAS00001000505","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000505","title":"Whole genome sequencing of chondrosarcoma","alternate_titles":[],"description":"Massive parallel sequencing of 10 chondrosarcoma genomes was conducted to identify somatic mutations, structural alterations including fusion genes and mutation signatures that may help to comprehensively characterize the molecular features.","alternate_descriptions":[],"data_types":["WGS"],"data_type_labels":["Whole genome sequencing"],"data_type_label":"Whole genome sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Chondrosarcoma\"); description-level mentions were not accepted. EGA study_type: Whole Genome Sequencing. Controlled access -- data require a Data Access Agreement. 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EGA study_type: Cancer Genomics. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Clear_Cell_Renal_Cell_Carcinoma","name":"Clear Cell Renal Cell Carcinoma","kind":"Disorder","source_path":"kb/disorders/Clear_Cell_Renal_Cell_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Clear_Cell_Renal_Cell_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Clear_Cell_Renal_Cell_Carcinoma.html#dataset-ega-egas00001000509"}],"context_names":["Clear Cell Renal Cell Carcinoma"],"disease_names":["Clear Cell Renal Cell Carcinoma"],"disease_name":"Clear Cell Renal Cell Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Clear_Cell_Renal_Cell_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Clear_Cell_Renal_Cell_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Clear_Cell_Renal_Cell_Carcinoma.html#dataset-ega-egas00001000509"]},{"id":"dataset:ega:egas00001000521","accession":"ega:EGAS00001000521","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000521","title":"Whole exome and whole genome sequencing of juvenile myelomonocytic leukemia (JMML)","alternate_titles":[],"description":"To obtain a complete registry of gene mutations in JMML, whole-exome sequencing was performed for paired tumor-normal DNA from 13 JMML cases, of which 2 cases were also analyzed by whole genome sequencing.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Juvenile Myelomonocytic Leukemia\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Juvenile_Myelomonocytic_Leukemia","name":"Juvenile Myelomonocytic Leukemia","kind":"Disorder","source_path":"kb/disorders/Juvenile_Myelomonocytic_Leukemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Juvenile_Myelomonocytic_Leukemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Juvenile_Myelomonocytic_Leukemia.html#dataset-ega-egas00001000521"}],"context_names":["Juvenile Myelomonocytic Leukemia"],"disease_names":["Juvenile Myelomonocytic Leukemia"],"disease_name":"Juvenile Myelomonocytic Leukemia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Juvenile_Myelomonocytic_Leukemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Juvenile_Myelomonocytic_Leukemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Juvenile_Myelomonocytic_Leukemia.html#dataset-ega-egas00001000521"]},{"id":"dataset:ega:egas00001000534","accession":"ega:EGAS00001000534","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000534","title":"Analysis of DNA methylation in normal B cells and chronic lymphocytic leukemia","alternate_titles":[],"description":"Charting differences between tumors and normal tissue is a mainstay of cancer research. However, clonal tumor expansion from complex normal tissue architectures potentially obscures cancer-specific events, including divergent epigenetic patterns. Using whole-genome bisulfite sequencing of normal B cell subsets, we observed broad epigenetic programming of selective transcription factor binding sites coincident with the degree of B cell maturation. By comparing normal B cells to malignant B cells from 268 patients with chronic lymphocytic leukemia (CLL), we showed that tumors derive largely from a continuum of maturation states reflected in normal developmental stages.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:24356097"],"publication_contexts":[{"context_id":"disorder:Chronic_Lymphocytic_Leukemia","publication":"PMID:24356097"}],"publication":"PMID:24356097","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/24356097","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Chronic Lymphocytic Leukemia\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Chronic_Lymphocytic_Leukemia","name":"Chronic Lymphocytic Leukemia","kind":"Disorder","source_path":"kb/disorders/Chronic_Lymphocytic_Leukemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Lymphocytic_Leukemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chronic_Lymphocytic_Leukemia.html#dataset-ega-egas00001000534"}],"context_names":["Chronic Lymphocytic Leukemia"],"disease_names":["Chronic Lymphocytic Leukemia"],"disease_name":"Chronic Lymphocytic Leukemia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chronic_Lymphocytic_Leukemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Lymphocytic_Leukemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chronic_Lymphocytic_Leukemia.html#dataset-ega-egas00001000534"]},{"id":"dataset:ega:egas00001000546","accession":"ega:EGAS00001000546","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000546","title":"Landscape of gene mutations in Down syndrome-related myeloid disorders","alternate_titles":[],"description":"To identify the spectrum of gene mutations in Down syndrome-related myeloid disorders, whole genome sequencing of 4 trio samples from TAM/AMKL/complete remission (CR) phases and whole exome sequencing of 15 TAM and 14 DS-AMKL samples were performed.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Down syndrome\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Down_syndrome","name":"Down_syndrome","kind":"Disorder","source_path":"kb/disorders/Down_syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Down_syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Down_syndrome.html#dataset-ega-egas00001000546"}],"context_names":["Down_syndrome"],"disease_names":["Down_syndrome"],"disease_name":"Down_syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Down_syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Down_syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Down_syndrome.html#dataset-ega-egas00001000546"]},{"id":"dataset:ega:egas00001000556","accession":"ega:EGAS00001000556","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000556","title":"Whole genome sequencing of autism spectrum disorder","alternate_titles":[],"description":"Autism Spectrum Disorder (ASD) demonstrates high heritability and familial clustering, yet the genetic causes remain only partially understood as a result of extensive clinical and genomic heterogeneity. Whole-genome sequencing (WGS) shows promise as a tool for identifying ASD risk genes as well as unreported mutations in known loci, but an assessment of its full utility in an ASD group has not been performed. We used WGS to examine 32 families with ASD to detect de novo or rare inherited genetic variants predicted to be deleterious (loss-of-function and damaging missense mutations).","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:23849776"],"publication_contexts":[{"context_id":"disorder:Autism_Spectrum_Disorder","publication":"PMID:23849776"}],"publication":"PMID:23849776","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/23849776","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Autism Spectrum Disorder\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Autism_Spectrum_Disorder","name":"Autism Spectrum Disorder","kind":"Disorder","source_path":"kb/disorders/Autism_Spectrum_Disorder.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autism_Spectrum_Disorder.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autism_Spectrum_Disorder.html#dataset-ega-egas00001000556"}],"context_names":["Autism Spectrum Disorder"],"disease_names":["Autism Spectrum Disorder"],"disease_name":"Autism Spectrum Disorder","same_context_model_ids":["model:kb/disorders/Autism_Spectrum_Disorder.yaml:Genotype-defined patient iPSC-derived neuronal networks","model:kb/disorders/Autism_Spectrum_Disorder.yaml:Multi-genotype human cortical organoid and neural-progenitor panel"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Autism_Spectrum_Disorder.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autism_Spectrum_Disorder.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Autism_Spectrum_Disorder.html#dataset-ega-egas00001000556"]},{"id":"dataset:ega:egas00001000557","accession":"ega:EGAS00001000557","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000557","title":"Whole exome sequencing of peripheral T-cell lymphoma (PTCL)","alternate_titles":[],"description":"Somatic mutations in 3 AITL and 3 PTCL, not otherwise specified (PTCL-NOS) specimens were explored using whole-exome sequencing.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Peripheral T-Cell Lymphoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Peripheral_T_Cell_Lymphoma","name":"Peripheral T-Cell Lymphoma","kind":"Disorder","source_path":"kb/disorders/Peripheral_T_Cell_Lymphoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Peripheral_T_Cell_Lymphoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Peripheral_T-Cell_Lymphoma.html#dataset-ega-egas00001000557"}],"context_names":["Peripheral T-Cell Lymphoma"],"disease_names":["Peripheral T-Cell Lymphoma"],"disease_name":"Peripheral T-Cell Lymphoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Peripheral_T_Cell_Lymphoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Peripheral_T_Cell_Lymphoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Peripheral_T-Cell_Lymphoma.html#dataset-ega-egas00001000557"]},{"id":"dataset:ega:egas00001000579","accession":"ega:EGAS00001000579","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000579","title":"Mutational analysis reveals the origin and therapy-driven evolution of recurrent glioma","alternate_titles":[],"description":"Tumor recurrence is a leading cause of cancer mortality. Therapies for recurrent disease may fail, at least in part, because the genomic alterations driving the growth of recurrences are distinct from those in the initial tumor. To explore this hypothesis, we sequenced the exomes of 23 initial low-grade gliomas and recurrent tumors resected from the same patients. In 43% of cases, at least half of the mutations in the initial tumor were undetected at recurrence, including driver mutations inTP53, ATRX, SMARCA4, and BRAF; this suggests that recurrent tumors are often seeded by cells derived from the initial tumor at a very early stage of their evolution.","alternate_descriptions":[],"data_types":["WES"],"data_type_labels":["Whole exome sequencing"],"data_type_label":"Whole exome sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:24336570"],"publication_contexts":[{"context_id":"disorder:Glioma","publication":"PMID:24336570"}],"publication":"PMID:24336570","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/24336570","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Glioma\"); description-level mentions were not accepted. EGA study_type: Exome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Glioma","name":"Glioma","kind":"Disorder","source_path":"kb/disorders/Glioma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Glioma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Glioma.html#dataset-ega-egas00001000579"}],"context_names":["Glioma"],"disease_names":["Glioma"],"disease_name":"Glioma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Glioma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Glioma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Glioma.html#dataset-ega-egas00001000579"]},{"id":"dataset:ega:egas00001000598","accession":"ega:EGAS00001000598","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000598","title":"RB1 Gene Inactivation by Chromothripsis in Human Retinoblastoma","alternate_titles":[],"description":"Retinoblastoma is a rare childhood cancer of the developing retina. Most retinoblastomas initiate with biallelic inactivation of the RB1 gene through diverse mechanisms including point mutations, nucleotide insertions, deletions, loss of heterozygosity and promoter hypermethylation. Recently, a novel mechanism of retinoblastoma initiation was proposed. Gallie and colleagues discovered that a small proportion of retinoblastomas lack RB1 mutations and had MYCN amplification [1]. In this study, we identified recurrent chromosomal, regional and focal genomic lesions in 94 primary retinoblastomas with their matched normal DNA using SNP 6.0 chips.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Retinoblastoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Retinoblastoma","name":"Retinoblastoma","kind":"Disorder","source_path":"kb/disorders/Retinoblastoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Retinoblastoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Retinoblastoma.html#dataset-ega-egas00001000598"}],"context_names":["Retinoblastoma"],"disease_names":["Retinoblastoma"],"disease_name":"Retinoblastoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Retinoblastoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Retinoblastoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Retinoblastoma.html#dataset-ega-egas00001000598"]},{"id":"dataset:ega:egas00001000624","accession":"ega:EGAS00001000624","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000624","title":"WTCCC2 project Glaucoma (GL) samples","alternate_titles":[],"description":"A WTCCC2 genome-wide association study for glaucoma (GL) in Australian individuals of European descent.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:23836780"],"publication_contexts":[{"context_id":"disorder:Glaucoma","publication":"PMID:23836780"}],"publication":"PMID:23836780","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/23836780","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Glaucoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Glaucoma","name":"Glaucoma","kind":"Disorder","source_path":"kb/disorders/Glaucoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Glaucoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Glaucoma.html#dataset-ega-egas00001000624"}],"context_names":["Glaucoma"],"disease_names":["Glaucoma"],"disease_name":"Glaucoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Glaucoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Glaucoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Glaucoma.html#dataset-ega-egas00001000624"]},{"id":"dataset:ega:egas00001000661","accession":"ega:EGAS00001000661","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000661","title":"Whole-exome analysis of corticotropin-independent Cushing's syndrome","alternate_titles":[],"description":"We performed WES for 8 cases with corticotropin-independent Cushing’s syndrome, in whom paired tumor and normal DNA was obtained from fresh frozen adenomas and either normal adrenal tissues or peripheral blood, respectively.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Cushing's Syndrome\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Cushings_Syndrome","name":"Cushing's Syndrome","kind":"Disorder","source_path":"kb/disorders/Cushings_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cushings_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cushing's_Syndrome.html#dataset-ega-egas00001000661"}],"context_names":["Cushing's Syndrome"],"disease_names":["Cushing's Syndrome"],"disease_name":"Cushing's Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cushings_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cushings_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cushing's_Syndrome.html#dataset-ega-egas00001000661"]},{"id":"dataset:ega:egas00001000662","accession":"ega:EGAS00001000662","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000662","title":"Biallelic DICER1 mutations in sporadic pleuropulmonary blastoma","alternate_titles":[],"description":"Pleuropulmonary blastoma (PPB) is an extremely rare pediatric malignancy in the lung, whose pathogenesis is poorly understood, except for recent reports of frequent germline heterozygous DICER1 mutations. To investigate the genetic basis of PPB, we performed whole-exome sequencing in 7 representative PPB cases, followed by targeted deep sequencing in 12 cases with PPB. DICER1 mutations were found in 11/12 cases. Biallelic DICER1 mutations were common in PPB, in which RNase IIIb domain mutations were found in all cases with or without nonsense/frameshift mutations and were somatic in all evaluable cases.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Pleuropulmonary Blastoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Pleuropulmonary_Blastoma","name":"Pleuropulmonary Blastoma","kind":"Disorder","source_path":"kb/disorders/Pleuropulmonary_Blastoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pleuropulmonary_Blastoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pleuropulmonary_Blastoma.html#dataset-ega-egas00001000662"}],"context_names":["Pleuropulmonary Blastoma"],"disease_names":["Pleuropulmonary Blastoma"],"disease_name":"Pleuropulmonary Blastoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Pleuropulmonary_Blastoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pleuropulmonary_Blastoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Pleuropulmonary_Blastoma.html#dataset-ega-egas00001000662"]},{"id":"dataset:ega:egas00001000693","accession":"ega:EGAS00001000693","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000693","title":"Neuromics / RD-Connect - congenital myasthenic syndrome","alternate_titles":[],"description":"This study contains omics datasets from the Neuromics project (www.rd-neuromics.eu) on rare neuromuscular and neurodegenerative disorders. Data includes BAM and VCF files from whole-exome sequencing and standardised phenotypic data mapped to the human phenotype ontology (HPO). In some cases proteomic, transcriptomic and metabolomic data may also be available. This study groups together datasets from individuals with a congenital myasthenic syndrome phenotype and also includes some unaffected family members. Search under the Neuromics name to find related studies for other neuromuscular and neurodegenerative disorders.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Congenital Myasthenic Syndrome\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Congenital_Myasthenic_Syndrome","name":"Congenital Myasthenic Syndrome","kind":"Disorder","source_path":"kb/disorders/Congenital_Myasthenic_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Congenital_Myasthenic_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Congenital_Myasthenic_Syndrome.html#dataset-ega-egas00001000693"}],"context_names":["Congenital Myasthenic Syndrome"],"disease_names":["Congenital Myasthenic Syndrome"],"disease_name":"Congenital Myasthenic Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Congenital_Myasthenic_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Congenital_Myasthenic_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Congenital_Myasthenic_Syndrome.html#dataset-ega-egas00001000693"]},{"id":"dataset:ega:egas00001000697","accession":"ega:EGAS00001000697","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000697","title":"Neuromics / RD-Connect - hereditary spastic paraplegia","alternate_titles":[],"description":"This study contains omics datasets from the Neuromics project (www.rd-neuromics.eu) on rare neuromuscular and neurodegenerative disorders. Data includes BAM and VCF files from whole-exome sequencing and standardised phenotypic data mapped to the human phenotype ontology (HPO). In some cases proteomic, transcriptomic and metabolomic data may also be available. This study groups together datasets from individuals with a hereditary spastic paraplegia phenotype, and also includes some unaffected family members. Search under the Neuromics name to find related studies for other neuromuscular and neurodegenerative disorders.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Hereditary Spastic Paraplegia\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Hereditary_Spastic_Paraplegia","name":"Hereditary Spastic Paraplegia","kind":"Disorder","source_path":"kb/disorders/Hereditary_Spastic_Paraplegia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hereditary_Spastic_Paraplegia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hereditary_Spastic_Paraplegia.html#dataset-ega-egas00001000697"}],"context_names":["Hereditary Spastic Paraplegia"],"disease_names":["Hereditary Spastic Paraplegia"],"disease_name":"Hereditary Spastic Paraplegia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hereditary_Spastic_Paraplegia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hereditary_Spastic_Paraplegia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hereditary_Spastic_Paraplegia.html#dataset-ega-egas00001000697"]},{"id":"dataset:ega:egas00001000734","accession":"ega:EGAS00001000734","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000734","title":"Genome wide association study on coronary heart disease in patients with familial hypercholesterolemia","alternate_titles":[],"description":"Mutations in the low-density lipoprotein receptor (LDLR) gene cause familial hypercholesterolemia (FH), a disorder characterized by coronary heart disease (CHD) at young age. We aimed to apply an extreme sampling method to enhance the statistical power to identify novel genetic risk variants for CHD in individuals with FH. We selected cases and controls with an extreme contrast in CHD risk from 17 000 FH patients from the Netherlands, whose functional LDLR mutation was unequivocally established.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Familial Hypercholesterolemia\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Familial_Hypercholesterolemia","name":"Familial Hypercholesterolemia","kind":"Disorder","source_path":"kb/disorders/Familial_Hypercholesterolemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Familial_Hypercholesterolemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Familial_Hypercholesterolemia.html#dataset-ega-egas00001000734"}],"context_names":["Familial Hypercholesterolemia"],"disease_names":["Familial Hypercholesterolemia"],"disease_name":"Familial Hypercholesterolemia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Familial_Hypercholesterolemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Familial_Hypercholesterolemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Familial_Hypercholesterolemia.html#dataset-ega-egas00001000734"]},{"id":"dataset:ega:egas00001000748","accession":"ega:EGAS00001000748","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000748","title":"GWA on coronary heart disease in patients with familial hypercholesterolemia (FH)","alternate_titles":[],"description":"Mutations in the low-density lipoprotein receptor (LDLR) gene cause familial hypercholesterolemia (FH), a disorder characterized by coronary heart disease (CHD) at young age. We aimed to apply an extreme sampling method to enhance the statistical power to identify novel genetic risk variants for CHD in individuals with FH. We selected cases and controls with an extreme contrast in CHD risk from 17 000 FH patients from the Netherlands, whose functional LDLR mutation was unequivocally established.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Familial Hypercholesterolemia\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Familial_Hypercholesterolemia","name":"Familial Hypercholesterolemia","kind":"Disorder","source_path":"kb/disorders/Familial_Hypercholesterolemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Familial_Hypercholesterolemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Familial_Hypercholesterolemia.html#dataset-ega-egas00001000748"}],"context_names":["Familial Hypercholesterolemia"],"disease_names":["Familial Hypercholesterolemia"],"disease_name":"Familial Hypercholesterolemia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Familial_Hypercholesterolemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Familial_Hypercholesterolemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Familial_Hypercholesterolemia.html#dataset-ega-egas00001000748"]},{"id":"dataset:ega:egas00001000767","accession":"ega:EGAS00001000767","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000767","title":"Next generation sequencing of sporadic schwannomatosis samples","alternate_titles":[],"description":"Schwannomatosis (MIM #162091) is characterized by the development of multiple schwannomas without vestibular nerve involvement (which is a characteristic of neurofibromatosis type 2 - NF2). In an effort to detect novel genetic alterations predisposing to schwannomatosis, we sequenced eight tumor-blood DNA pairs from de novo schwannomatosis patients. The results of our study are present in the paper \"Whole exome sequencing reveals that the majority of schwannomatosis cases remain unexplained after excluding SMARCB1 and LZTR1 germline variants\" published in Acta Neuropathologica (PMID:25008767)","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:25008767"],"publication_contexts":[{"context_id":"disorder:Schwannomatosis","publication":"PMID:25008767"}],"publication":"PMID:25008767","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/25008767","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Schwannomatosis\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Schwannomatosis","name":"Schwannomatosis","kind":"Disorder","source_path":"kb/disorders/Schwannomatosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Schwannomatosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Schwannomatosis.html#dataset-ega-egas00001000767"}],"context_names":["Schwannomatosis"],"disease_names":["Schwannomatosis"],"disease_name":"Schwannomatosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Schwannomatosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Schwannomatosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Schwannomatosis.html#dataset-ega-egas00001000767"]},{"id":"dataset:ega:egas00001000773","accession":"ega:EGAS00001000773","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000773","title":"WTCCC2 Visceral Leishmaniasis (VL) samples","alternate_titles":[],"description":"A WTCCC2 project genome-wide association study for visceral leishmaniasis (VL) in individuals from India, Brazil and Sudan, genotyped on the custom Illumina 670k array. The WTCCC2 analysis of the Brazilian and Indian samples is described in Fakiola et al. [Nat Genet. 2013 Feb;45(2):208-13].It should be noted that due to expected family structure in the data, normal analyses of these data should include an estimation of the relatedness between the samples. For more details about sample collection for the project please refer to the Methods section of the paper above. The samples from India were all collected from Bihar state in northeastern India.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:23291585"],"publication_contexts":[{"context_id":"disorder:Leishmaniasis","publication":"PMID:23291585"}],"publication":"PMID:23291585","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/23291585","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Leishmaniasis\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Leishmaniasis","name":"Leishmaniasis","kind":"Disorder","source_path":"kb/disorders/Leishmaniasis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Leishmaniasis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Leishmaniasis.html#dataset-ega-egas00001000773"}],"context_names":["Leishmaniasis"],"disease_names":["Leishmaniasis"],"disease_name":"Leishmaniasis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Leishmaniasis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Leishmaniasis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Leishmaniasis.html#dataset-ega-egas00001000773"]},{"id":"dataset:ega:egas00001000829","accession":"ega:EGAS00001000829","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000829","title":"Detection of Clinically Relevant Genetic Variants in Autism spectrum Disorder by Whole-Genome Sequencing","alternate_titles":[],"description":"Autism Spectrum Disorder (ASD) demonstrates high heritability and familial clustering, yet the genetic causes remain only partially understood as a result of extensive clinical and genomic heterogeneity. Whole-genome sequencing (WGS) shows promise as a tool for identifying ASD risk genes as well as unreported mutations in known loci, but an assessment of its full utility in an ASD group has not been performed. We used WGS to examine 32 families with ASD to detect de novo or rare inherited genetic variants predicted to be deleterious (loss-of-function and damaging missense mutations).","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Autism Spectrum Disorder\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Autism_Spectrum_Disorder","name":"Autism Spectrum Disorder","kind":"Disorder","source_path":"kb/disorders/Autism_Spectrum_Disorder.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autism_Spectrum_Disorder.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autism_Spectrum_Disorder.html#dataset-ega-egas00001000829"}],"context_names":["Autism Spectrum Disorder"],"disease_names":["Autism Spectrum Disorder"],"disease_name":"Autism Spectrum Disorder","same_context_model_ids":["model:kb/disorders/Autism_Spectrum_Disorder.yaml:Genotype-defined patient iPSC-derived neuronal networks","model:kb/disorders/Autism_Spectrum_Disorder.yaml:Multi-genotype human cortical organoid and neural-progenitor panel"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Autism_Spectrum_Disorder.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autism_Spectrum_Disorder.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Autism_Spectrum_Disorder.html#dataset-ega-egas00001000829"]},{"id":"dataset:ega:egas00001000839","accession":"ega:EGAS00001000839","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000839","title":"Targeting the DNA Repair Pathway in Ewing Sarcoma","alternate_titles":[],"description":"Ewing’s Sarcoma is a bone and soft tissue tumor that primarily affects adolescents and young adults. With current therapies, 70% of patients with localized disease survive but survival for metastatic and recurrent disease is poor. Whole genome sequencing of 19 Ewing’s Sarcoma tumors showed that STAG2 was mutated in 10% (2/19) of the tumors and STAG2 protein was absent in 14% (13/106) tumors by immunohistochemical staining. Previous studies have shown that glioblastoma cells lacking STAG2 are more sensitive to poly-ADP ribose polymerase (PARP) inhibitors. We found that Ewing’s Sarcoma cell lines are sensitive to PARP inhibitors irrespective of STAG2 protein expression.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Ewing Sarcoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Ewing_Sarcoma","name":"Ewing Sarcoma","kind":"Disorder","source_path":"kb/disorders/Ewing_Sarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ewing_Sarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#dataset-ega-egas00001000839"}],"context_names":["Ewing Sarcoma"],"disease_names":["Ewing Sarcoma"],"disease_name":"Ewing Sarcoma","same_context_model_ids":["model:kb/disorders/Ewing_Sarcoma.yaml:BARD1-variant PSaRC318 and BARD1-depleted Ewing cells","model:kb/disorders/Ewing_Sarcoma.yaml:Ewing sarcoma tumor organoid model systems","model:kb/disorders/Ewing_Sarcoma.yaml:Flow-perfusion Ewing sarcoma 3D scaffold coculture","model:kb/disorders/Ewing_Sarcoma.yaml:Human embryonic mesenchymal stem cell EWS-FLI1 transformation model","model:kb/disorders/Ewing_Sarcoma.yaml:Patient-derived Ewing sarcoma culture panel"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Ewing_Sarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ewing_Sarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#dataset-ega-egas00001000839"]},{"id":"dataset:ega:egas00001000841","accession":"ega:EGAS00001000841","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000841","title":"HumanMethylation450K data from Purified Plasma Cells of Monoclonal gammopathy of unknown significance and Multiple myeloma patients and Healthy donors","alternate_titles":[],"description":"HumanMethylation450K data from Purified Plasma Cells of Monoclonal gammopathy of unknown significance and Multiple myeloma patients and Healthy donors","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Multiple Myeloma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Multiple_Myeloma","name":"Multiple Myeloma","kind":"Disorder","source_path":"kb/disorders/Multiple_Myeloma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Multiple_Myeloma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Multiple_Myeloma.html#dataset-ega-egas00001000841"}],"context_names":["Multiple Myeloma"],"disease_names":["Multiple Myeloma"],"disease_name":"Multiple Myeloma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Multiple_Myeloma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Multiple_Myeloma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Multiple_Myeloma.html#dataset-ega-egas00001000841"]},{"id":"dataset:ega:egas00001000843","accession":"ega:EGAS00001000843","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000843","title":"Genomic analysis of Smoothened inhibitor resistance in basal cell carcinoma","alternate_titles":[],"description":"Genomic analysis of Smoothened inhibitor resistance in basal cell carcinoma","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Basal Cell Carcinoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Basal_Cell_Carcinoma","name":"Basal Cell Carcinoma","kind":"Disorder","source_path":"kb/disorders/Basal_Cell_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Basal_Cell_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Basal_Cell_Carcinoma.html#dataset-ega-egas00001000843"}],"context_names":["Basal Cell Carcinoma"],"disease_names":["Basal Cell Carcinoma"],"disease_name":"Basal Cell Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Basal_Cell_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Basal_Cell_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Basal_Cell_Carcinoma.html#dataset-ega-egas00001000843"]},{"id":"dataset:ega:egas00001000845","accession":"ega:EGAS00001000845","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000845","title":"Genomic analysis of Smoothened inhibitor resistance in basal cell carcinoma","alternate_titles":[],"description":"Smoothened inhibitors are currently being investigated for the treatment of several cancers. Vismodegib is approved for the treatment of locally advanced and metastatic basal cell carcinoma (BCC). The majority of BCC patients treated with vismodegib experience significant clinical benefit, however, a small number of patients develop resistance. Knowledge of resistance mechanisms can generate predictive biomarkers and is critical for the design of additional therapeutic strategies aimed at circumventing resistance.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Basal Cell Carcinoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Basal_Cell_Carcinoma","name":"Basal Cell Carcinoma","kind":"Disorder","source_path":"kb/disorders/Basal_Cell_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Basal_Cell_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Basal_Cell_Carcinoma.html#dataset-ega-egas00001000845"}],"context_names":["Basal Cell Carcinoma"],"disease_names":["Basal Cell Carcinoma"],"disease_name":"Basal Cell Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Basal_Cell_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Basal_Cell_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Basal_Cell_Carcinoma.html#dataset-ega-egas00001000845"]},{"id":"dataset:ega:egas00001000849","accession":"ega:EGAS00001000849","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000849","title":"Celiac disease case-control North Indian Immunochip dataset","alternate_titles":[],"description":"Illumina Immunochip genotype data for coeliac disease and control samples of North Indian samples origin. Data is in PLINK binary format. Calling algorithm for genotypes is based on GenomeStudio (GenTrain), with manual clustering of selected variants.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Celiac Disease\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Celiac_Disease","name":"Celiac Disease","kind":"Disorder","source_path":"kb/disorders/Celiac_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Celiac_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Celiac_Disease.html#dataset-ega-egas00001000849"}],"context_names":["Celiac Disease"],"disease_names":["Celiac Disease"],"disease_name":"Celiac Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Celiac_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Celiac_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Celiac_Disease.html#dataset-ega-egas00001000849"]},{"id":"dataset:ega:egas00001000853","accession":"ega:EGAS00001000853","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000853","title":"Whole exome sequencing for gallbladder cancer in Xinhua Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine","alternate_titles":[],"description":"Patients with gallbladder carcinoma (GBC), the most aggressive malignancy of the biliary tract, have a poor prognosis. Here, we report our identification of somatic mutations of GBCs in 57 tumor-normal pairs by use of a combination of exome sequencing and ultra-deep sequencing of cancer-related genes. The mutation pattern is defined by a dominative prevalence of C>T mutations at TCN sites. Genes with a significant frequency of non-silent mutations include TP53 (47.1%), KRAS (7.8%), and ERBB3 (11.8%). Moreover, ErbB signaling (including EGFR, ERBB2, ERBB3, ERBB4 and their downstream genes) is the most extensively mutated pathway, affecting 36.8% (21 of 57) of the GBC samples.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Gallbladder Cancer\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Gallbladder_Cancer","name":"Gallbladder Cancer","kind":"Disorder","source_path":"kb/disorders/Gallbladder_Cancer.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Gallbladder_Cancer.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Gallbladder_Cancer.html#dataset-ega-egas00001000853"}],"context_names":["Gallbladder Cancer"],"disease_names":["Gallbladder Cancer"],"disease_name":"Gallbladder Cancer","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Gallbladder_Cancer.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Gallbladder_Cancer.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Gallbladder_Cancer.html#dataset-ega-egas00001000853"]},{"id":"dataset:ega:egas00001000855","accession":"ega:EGAS00001000855","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000855","title":"Genomic landscape of Ewing sarcoma (ICGC project)","alternate_titles":[],"description":"The Ewing sarcoma project aims to sequence 100 complete genomes of cells of patients suffering from this disease. It is an initiative of great projection, since this is the second most common bone tumor in children and teenagers. The goal of the project is to establish the catalogue of somatic mutations that may cooperate with EWS-ETS fusion in the development of the tumor. The Ewing sarcoma project aims to perform 100 whole genome sequencing of germline and tumor DNA as well as at least 50 RNA-seq from tumors. Correlations between molecular profiles and clinical features will be established.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:25223734"],"publication_contexts":[{"context_id":"disorder:Ewing_Sarcoma","publication":"PMID:25223734"}],"publication":"PMID:25223734","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/25223734","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Ewing Sarcoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Ewing_Sarcoma","name":"Ewing Sarcoma","kind":"Disorder","source_path":"kb/disorders/Ewing_Sarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ewing_Sarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#dataset-ega-egas00001000855"}],"context_names":["Ewing Sarcoma"],"disease_names":["Ewing Sarcoma"],"disease_name":"Ewing Sarcoma","same_context_model_ids":["model:kb/disorders/Ewing_Sarcoma.yaml:BARD1-variant PSaRC318 and BARD1-depleted Ewing cells","model:kb/disorders/Ewing_Sarcoma.yaml:Ewing sarcoma tumor organoid model systems","model:kb/disorders/Ewing_Sarcoma.yaml:Flow-perfusion Ewing sarcoma 3D scaffold coculture","model:kb/disorders/Ewing_Sarcoma.yaml:Human embryonic mesenchymal stem cell EWS-FLI1 transformation model","model:kb/disorders/Ewing_Sarcoma.yaml:Patient-derived Ewing sarcoma culture panel"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Ewing_Sarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ewing_Sarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#dataset-ega-egas00001000855"]},{"id":"dataset:ega:egas00001000875","accession":"ega:EGAS00001000875","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000875","title":"Loss of functional mutation in RPL27 and RPS27 identified by whole-exome sequencing in Diamond-Blackfan Anemia","alternate_titles":[],"description":"We performed whole-exome sequencing analysis of 48 patients with no documented mutations/deletions involving known Diamond-Blackfan anemia genes and identified 10 mutations in previous known causative genes and 2 mutations in novel ribosomal genes.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Diamond-Blackfan Anemia\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Diamond-Blackfan_Anemia","name":"Diamond-Blackfan Anemia","kind":"Disorder","source_path":"kb/disorders/Diamond-Blackfan_Anemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Diamond-Blackfan_Anemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Diamond-Blackfan_Anemia.html#dataset-ega-egas00001000875"}],"context_names":["Diamond-Blackfan Anemia"],"disease_names":["Diamond-Blackfan Anemia"],"disease_name":"Diamond-Blackfan Anemia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Diamond-Blackfan_Anemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Diamond-Blackfan_Anemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Diamond-Blackfan_Anemia.html#dataset-ega-egas00001000875"]},{"id":"dataset:ega:egas00001000885","accession":"ega:EGAS00001000885","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000885","title":"Whole Genome Sequencing to track subclonal heterogeneity in 18  samples from 3 Chronic Lymphocytic Leukemia patients subjected to repeated cycles of therapy.","alternate_titles":[],"description":"This study took 18 samples from three patients with Chronic Lymphocytic Leukemia. The 3 CLL patients received multiple different treatments sequentially for a period of up to 7 years. Peripheral blood samples were taken at 5 specific time points during disease progression together with 1 matched buccal swab per patient. All the selected patients had unmutated IgVH status reflecting poor prognosis. However, none of the patients had complex genomic aberrations associated with aggressive disease. Peripheral blood samples and buccal smears were obtained from patients, who had given informed consent for sequential sample collection and analysis.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Chronic Lymphocytic Leukemia\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Chronic_Lymphocytic_Leukemia","name":"Chronic Lymphocytic Leukemia","kind":"Disorder","source_path":"kb/disorders/Chronic_Lymphocytic_Leukemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Lymphocytic_Leukemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chronic_Lymphocytic_Leukemia.html#dataset-ega-egas00001000885"}],"context_names":["Chronic Lymphocytic Leukemia"],"disease_names":["Chronic Lymphocytic Leukemia"],"disease_name":"Chronic Lymphocytic Leukemia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chronic_Lymphocytic_Leukemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Lymphocytic_Leukemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chronic_Lymphocytic_Leukemia.html#dataset-ega-egas00001000885"]},{"id":"dataset:ega:egas00001000936","accession":"ega:EGAS00001000936","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000936","title":"Ischemic stroke in a Swedish case-control study.","alternate_titles":[],"description":"Background. Genetic risk scores (GRS), summing up the total effect of several single nucleotide polymorphisms (SNPs) in genes associated with either coronary risk or cardiovascular risk factors, have been tested for association with ischemic stroke with conflicting results. Recently an association was found between a GRS, based on 29 SNPs discovered by genome-wide association studies (GWAS) and hypertension. The aim of our study was to investigate the possible association of the same GRS with ischemic stroke on top of other “traditional risk factors”, also testing its potential improvement in indices of discrimination and reclassification, in a Swedish case-control study.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Ischemic Stroke\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Ischemic_Stroke","name":"Ischemic Stroke","kind":"Disorder","source_path":"kb/disorders/Ischemic_Stroke.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ischemic_Stroke.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Ischemic_Stroke.html#dataset-ega-egas00001000936"}],"context_names":["Ischemic Stroke"],"disease_names":["Ischemic Stroke"],"disease_name":"Ischemic Stroke","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Ischemic_Stroke.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ischemic_Stroke.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Ischemic_Stroke.html#dataset-ega-egas00001000936"]},{"id":"dataset:ega:egas00001000962","accession":"ega:EGAS00001000962","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000962","title":"Plasma DNA aberrations in systemic lupus erythematosus revealed by genomic and methylomic sequencing","alternate_titles":[],"description":"We performed a high-resolution analysis of the biological characteristics of plasma DNA in systemic lupus erythematosus (SLE) patients using massively parallel genomic and methylomic sequencing. A number of plasma DNA abnormalities were found. First, aberrations in measured genomic representations (MGRs) were identified in the plasma DNA of SLE patients. The extent of the aberrations in MGRs correlated with anti-double–stranded DNA (anti-dsDNA) antibody level. Second, the plasma DNA of active SLE patients exhibited skewed molecular size-distribution profiles with a significantly increased proportion of short DNA fragments.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:25427797"],"publication_contexts":[{"context_id":"disorder:Systemic_Lupus_Erythematosus","publication":"PMID:25427797"}],"publication":"PMID:25427797","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/25427797","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Systemic Lupus Erythematosus\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Systemic_Lupus_Erythematosus","name":"Systemic Lupus Erythematosus","kind":"Disorder","source_path":"kb/disorders/Systemic_Lupus_Erythematosus.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Systemic_Lupus_Erythematosus.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Systemic_Lupus_Erythematosus.html#dataset-ega-egas00001000962"}],"context_names":["Systemic Lupus Erythematosus"],"disease_names":["Systemic Lupus Erythematosus"],"disease_name":"Systemic Lupus Erythematosus","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Systemic_Lupus_Erythematosus.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Systemic_Lupus_Erythematosus.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Systemic_Lupus_Erythematosus.html#dataset-ega-egas00001000962"]},{"id":"dataset:ega:egas00001000990","accession":"ega:EGAS00001000990","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001000990","title":"Fetal hemoglobin in sickle cell disease patients from Tanzania","alternate_titles":[],"description":"Levels of fetal hemoglobin have been associated with differences in severity and outcome of sickle cell disease (SCD). While some genetic associations have been reported between SNPs and HbF level, little of the variance in the trait is explained, and most studies have focused on African American, rather than African samples. We have carried out a GWAS in a collection of SCD patients from Dar es Salaam, Tanzania. This sample represents a diverse, metropolitan collection of individuals from East Africa. Omni 2.5M genotypes and HbF levels (measured after 5 years of age) are available.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Sickle Cell Disease\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Sickle_Cell_Disease","name":"Sickle Cell Disease","kind":"Disorder","source_path":"kb/disorders/Sickle_Cell_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sickle_Cell_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Sickle_Cell_Disease.html#dataset-ega-egas00001000990"}],"context_names":["Sickle Cell Disease"],"disease_names":["Sickle Cell Disease"],"disease_name":"Sickle Cell Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Sickle_Cell_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sickle_Cell_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Sickle_Cell_Disease.html#dataset-ega-egas00001000990"]},{"id":"dataset:ega:egas00001001018","accession":"ega:EGAS00001001018","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001001018","title":"Whole-genome plasma sequencing reveals focal amplifications as a driving force in metastatic prostate cancer","alternate_titles":[],"description":"Genomic alterations in metastatic prostate cancer remain incompletely characterized. Here we analyze 493 prostate cancer cases from the TCGA database and perform whole-genome plasma sequencing on 95 plasma samples derived from 43 patients with metastatic prostate cancer. From these samples, we identify established driver aberrations in a cancer-related gene in nearly all cases (97.7%), including driver gene fusions (TMPRSS2:ERG), driver focal deletions (PTEN, RYBP, SHQ1), and driver amplifications (AR, MYC). In serial plasma analyses, we observe changes in focal amplifications in 40% of cases.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Metastatic Prostate Cancer\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Prostate_Adenocarcinoma","name":"Prostate Adenocarcinoma","kind":"Disorder","source_path":"kb/disorders/Prostate_Adenocarcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Prostate_Adenocarcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Prostate_Adenocarcinoma.html#dataset-ega-egas00001001018"}],"context_names":["Prostate Adenocarcinoma"],"disease_names":["Prostate Adenocarcinoma"],"disease_name":"Prostate Adenocarcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Prostate_Adenocarcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Prostate_Adenocarcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Prostate_Adenocarcinoma.html#dataset-ega-egas00001001018"]},{"id":"dataset:ega:egas00001001025","accession":"ega:EGAS00001001025","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001001025","title":"Comprehensive miRNA Sequence Analysis Reveals Survival Differences in Diffuse Large B-cell Lymphoma Patients","alternate_titles":[],"description":"Diffuse large B-cell lymphoma (DLBCL) is an aggressive disease, with 30-40% of patients failing to achieve complete responses to standard therapy. miRNAs are RNA molecules that attenuate expression of their mRNA targets. To characterize the DLBCL miRNome, we sequenced miRNAs from 92 DLBCL and 15 benign centroblast fresh frozen samples and from 140 DLBCL formalin-fixed, paraffin-embedded tissue (FFPET) samples for validation.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Diffuse Large B-Cell Lymphoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Diffuse_Large_B_Cell_Lymphoma","name":"Diffuse Large B-Cell Lymphoma","kind":"Disorder","source_path":"kb/disorders/Diffuse_Large_B_Cell_Lymphoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Diffuse_Large_B_Cell_Lymphoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Diffuse_Large_B-Cell_Lymphoma.html#dataset-ega-egas00001001025"}],"context_names":["Diffuse Large B-Cell Lymphoma"],"disease_names":["Diffuse Large B-Cell Lymphoma"],"disease_name":"Diffuse Large B-Cell Lymphoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Diffuse_Large_B_Cell_Lymphoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Diffuse_Large_B_Cell_Lymphoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Diffuse_Large_B-Cell_Lymphoma.html#dataset-ega-egas00001001025"]},{"id":"dataset:ega:egas00001001048","accession":"ega:EGAS00001001048","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001001048","title":"Preeclampsia InterPregGen Consortium: GWAS meta-analysis summary statistics for European fetal preeclampsia cases versus controls and GWAS genotype data for European fetal preeclampsia cases","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:28628106"],"publication_contexts":[{"context_id":"disorder:Preeclampsia","publication":"PMID:28628106"}],"publication":"PMID:28628106","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/28628106","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Preeclampsia\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Preeclampsia","name":"Preeclampsia","kind":"Disorder","source_path":"kb/disorders/Preeclampsia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Preeclampsia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Preeclampsia.html#dataset-ega-egas00001001048"}],"context_names":["Preeclampsia"],"disease_names":["Preeclampsia"],"disease_name":"Preeclampsia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Preeclampsia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Preeclampsia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Preeclampsia.html#dataset-ega-egas00001001048"]},{"id":"dataset:ega:egas00001001067","accession":"ega:EGAS00001001067","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001001067","title":"Integrated genomic, transcriptional and epigenomic analyses in germinal center-cell lymphomas link the mutation landscape with differential DNA methylation in Burkitt lymphoma","alternate_titles":[],"description":"Biologically and clinically diverse B-cell neoplasms, including Burkitt, follicular and diffuse large B-cell lymphoma, show features of germinal center (GC) B-cells. Here we present a comprehensive analysis of the epigenetic landscape of GC-B-cell lymphomas using whole genome bisulfite sequencing paired with genome and transcriptome sequencing from 29 primary tumor samples and four normal GC-B-cell samples. All lymphomas studied showed extensive genome-wide methylation losses as well as intragenic regions where DNA methylation levels were strongly correlated with expression of associated genes.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Burkitt Lymphoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Burkitt_Lymphoma","name":"Burkitt Lymphoma","kind":"Disorder","source_path":"kb/disorders/Burkitt_Lymphoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Burkitt_Lymphoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Burkitt_Lymphoma.html#dataset-ega-egas00001001067"}],"context_names":["Burkitt Lymphoma"],"disease_names":["Burkitt Lymphoma"],"disease_name":"Burkitt Lymphoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Burkitt_Lymphoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Burkitt_Lymphoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Burkitt_Lymphoma.html#dataset-ega-egas00001001067"]},{"id":"dataset:ega:egas00001001089","accession":"ega:EGAS00001001089","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001001089","title":"Russian GWAS of tuberculosis","alternate_titles":[],"description":"Genome-wide association study of cases of tuberculosis from St. Petersburg and Samara, in Russia, compared to healthy controls from the same two cities. Genotyped using the Affy6 platform.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Tuberculosis\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Tuberculosis","name":"Tuberculosis","kind":"Disorder","source_path":"kb/disorders/Tuberculosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Tuberculosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Tuberculosis.html#dataset-ega-egas00001001089"}],"context_names":["Tuberculosis"],"disease_names":["Tuberculosis"],"disease_name":"Tuberculosis","same_context_model_ids":["model:kb/disorders/Tuberculosis.yaml:Autologous iPSC-derived alveolus-on-chip (iLoC) Mtb infection model"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Tuberculosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Tuberculosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Tuberculosis.html#dataset-ega-egas00001001089"]},{"id":"dataset:ega:egas00001001090","accession":"ega:EGAS00001001090","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001001090","title":"GWAS of tuberculosis in Russia","alternate_titles":[],"description":"Genome-wide association study of cases of tuberculosis from St Petersburg and Samara, in Russia, compared to healthy controls from the same two cities. Genotype data from Affy6 array.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Tuberculosis\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Tuberculosis","name":"Tuberculosis","kind":"Disorder","source_path":"kb/disorders/Tuberculosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Tuberculosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Tuberculosis.html#dataset-ega-egas00001001090"}],"context_names":["Tuberculosis"],"disease_names":["Tuberculosis"],"disease_name":"Tuberculosis","same_context_model_ids":["model:kb/disorders/Tuberculosis.yaml:Autologous iPSC-derived alveolus-on-chip (iLoC) Mtb infection model"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Tuberculosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Tuberculosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Tuberculosis.html#dataset-ega-egas00001001090"]},{"id":"dataset:ega:egas00001001098","accession":"ega:EGAS00001001098","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001001098","title":"Compound heterozygous mutations in the noncoding RNU4ATAC gene cause Roifman Syndrome by disrupting minor intron splicing","alternate_titles":[],"description":"Roifman Syndrome is a rare congenital disorder characterized by growth retardation, cognitive delay, spondyloepiphyseal dysplasia and antibody deficiency. Given its prevalence in males, it was originally postulated to be X-linked. Whole genome sequencing revealed compound heterozygous rare variants disrupting highly conserved positions of the autosomal non-coding RNU4ATAC gene, a minor spliceosome component essential for minor intron splicing. Targeted sequencing confirmed allele segregation in six cases from four unrelated families.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Roifman syndrome\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Roifman-syndrome","name":"Roifman-syndrome","kind":"Disorder","source_path":"kb/disorders/Roifman-syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Roifman-syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Roifman-syndrome.html#dataset-ega-egas00001001098"}],"context_names":["Roifman-syndrome"],"disease_names":["Roifman-syndrome"],"disease_name":"Roifman-syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Roifman-syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Roifman-syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Roifman-syndrome.html#dataset-ega-egas00001001098"]},{"id":"dataset:ega:egas00001001110","accession":"ega:EGAS00001001110","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001001110","title":"Blueprint RNAseq profile of purified plasma cells from multiple myeloma patients and tonsils of healthy donors","alternate_titles":[],"description":"In the context of an epigenomic study of multiple myeloma, a have generated RNAseq profiles of purified plasma cells from 11 multiple myeloma patients and tonsils of 4 healthy donors","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Multiple Myeloma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Multiple_Myeloma","name":"Multiple Myeloma","kind":"Disorder","source_path":"kb/disorders/Multiple_Myeloma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Multiple_Myeloma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Multiple_Myeloma.html#dataset-ega-egas00001001110"}],"context_names":["Multiple Myeloma"],"disease_names":["Multiple Myeloma"],"disease_name":"Multiple Myeloma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Multiple_Myeloma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Multiple_Myeloma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Multiple_Myeloma.html#dataset-ega-egas00001001110"]},{"id":"dataset:ega:egas00001001147","accession":"ega:EGAS00001001147","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001001147","title":"463 newly diagnosed patients with Multiple Myeloma underwent whole exome sequencing of tumour and peripheral blood DNA.","alternate_titles":[],"description":"463 newly diagnosed patients from the UK Myeloma XI clinical trial (NCT01554852) underwent whole exome sequencing plus targeted capture of the IGH/K/L and MYC loci. 200 ng of DNA were processed using NEBNext DNA library prepartion kit and hybridised to the SureSelect Human All Exon V5 Plus. Four samples were pooled and run on one lane of a HiSeq 2000 using 76-bp paired end reads. DNA from CD138+ selected bone marrow cells (myeloma tumour) as well as peripheral white blood cells were analysed and somatic mutations detected.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:25904160"],"publication_contexts":[{"context_id":"disorder:Multiple_Myeloma","publication":"PMID:25904160"}],"publication":"PMID:25904160","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/25904160","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Multiple Myeloma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Multiple_Myeloma","name":"Multiple Myeloma","kind":"Disorder","source_path":"kb/disorders/Multiple_Myeloma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Multiple_Myeloma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Multiple_Myeloma.html#dataset-ega-egas00001001147"}],"context_names":["Multiple Myeloma"],"disease_names":["Multiple Myeloma"],"disease_name":"Multiple Myeloma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Multiple_Myeloma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Multiple_Myeloma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Multiple_Myeloma.html#dataset-ega-egas00001001147"]},{"id":"dataset:ega:egas00001001190","accession":"ega:EGAS00001001190","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001001190","title":"Recurrent mTORC1-activating RRAGC mutations in follicular lymphoma","alternate_titles":[],"description":"Follicular lymphoma (FL) is an incurable B-cell malignancy characterized by the t(14;18) and mutations in one or more components of the epigenome. Whilst frequent gene mutations in signaling pathways, including JAK-STAT, NOTCH and NF-κB, have also been defined, the spectrum of these mutations typically overlap with the closely-related diffuse large B cell lymphoma (DLBCL). A combination of discovery exome and extended targeted sequencing revealed recurrent somatic mutations in RRAGC uniquely enriched in FL patients (17%).","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Follicular Lymphoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Follicular_Lymphoma","name":"Follicular Lymphoma","kind":"Disorder","source_path":"kb/disorders/Follicular_Lymphoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Follicular_Lymphoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Follicular_Lymphoma.html#dataset-ega-egas00001001190"}],"context_names":["Follicular Lymphoma"],"disease_names":["Follicular Lymphoma"],"disease_name":"Follicular Lymphoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Follicular_Lymphoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Follicular_Lymphoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Follicular_Lymphoma.html#dataset-ega-egas00001001190"]},{"id":"dataset:ega:egas00001001199","accession":"ega:EGAS00001001199","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001001199","title":"MINCR is a MYC-induced lncRNA able to modulate MYC’s transcriptional network in Burkitt lymphoma cells","alternate_titles":[],"description":"Despite the established role of the transcription factor MYC in cancer, little is known about the involvement of lncRNAs in mediating MYC’s function. Here we have intersected RNA-sequencing data from MYC-inducible cell lines, from a cohort of 91 mature B-cell lymphomas and from sorted germinal-center B-cells. By this approach, we identified 13 lncRNAs differentially expressed in IG-MYC-positive Burkitt lymphoma and regulated by MYC in the model cell lines. Among them we focused on a lncRNA that we named MINCR, showing a strong correlation with MYC expression in MYC-positive lymphomas and in pancreatic ductal adenocarcinomas.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Burkitt Lymphoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Burkitt_Lymphoma","name":"Burkitt Lymphoma","kind":"Disorder","source_path":"kb/disorders/Burkitt_Lymphoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Burkitt_Lymphoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Burkitt_Lymphoma.html#dataset-ega-egas00001001199"}],"context_names":["Burkitt Lymphoma"],"disease_names":["Burkitt Lymphoma"],"disease_name":"Burkitt Lymphoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Burkitt_Lymphoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Burkitt_Lymphoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Burkitt_Lymphoma.html#dataset-ega-egas00001001199"]},{"id":"dataset:ega:egas00001001210","accession":"ega:EGAS00001001210","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001001210","title":"Whole Genome sequencing of adult T-cell leukemia/lymphoma","alternate_titles":[],"description":"Whole Genome sequencing of a single adult T-cell leukemia/lymphoma case","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Adult T-Cell Leukemia/Lymphoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Adult_T_Cell_Leukemia_Lymphoma","name":"Adult T-Cell Leukemia/Lymphoma","kind":"Disorder","source_path":"kb/disorders/Adult_T_Cell_Leukemia_Lymphoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Adult_T_Cell_Leukemia_Lymphoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Adult_T-Cell_Leukemia_Lymphoma.html#dataset-ega-egas00001001210"}],"context_names":["Adult T-Cell Leukemia/Lymphoma"],"disease_names":["Adult T-Cell Leukemia/Lymphoma"],"disease_name":"Adult T-Cell Leukemia/Lymphoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Adult_T_Cell_Leukemia_Lymphoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Adult_T_Cell_Leukemia_Lymphoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Adult_T-Cell_Leukemia_Lymphoma.html#dataset-ega-egas00001001210"]},{"id":"dataset:ega:egas00001001214","accession":"ega:EGAS00001001214","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001001214","title":"Whole genome and transcriptome analysis of anaplastic thyroid carcinoma","alternate_titles":[],"description":"Whole genome and transcriptome analysis of anaplastic thyroid carcinoma","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Anaplastic Thyroid Carcinoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Anaplastic_Thyroid_Carcinoma","name":"Anaplastic Thyroid Carcinoma","kind":"Disorder","source_path":"kb/disorders/Anaplastic_Thyroid_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Anaplastic_Thyroid_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Anaplastic_Thyroid_Carcinoma.html#dataset-ega-egas00001001214"}],"context_names":["Anaplastic Thyroid Carcinoma"],"disease_names":["Anaplastic Thyroid Carcinoma"],"disease_name":"Anaplastic Thyroid Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Anaplastic_Thyroid_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Anaplastic_Thyroid_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Anaplastic_Thyroid_Carcinoma.html#dataset-ega-egas00001001214"]},{"id":"dataset:ega:egas00001001258","accession":"ega:EGAS00001001258","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001001258","title":"Search for new loci and low-frequency variants influencing glioma risk by exome-array analysis","alternate_titles":[],"description":"To identify protein altering variants (PAVs) for glioma we analysed Illumina HumanExome BeadChip exome array data on 1,882 glioma cases and 8,079 controls from three independent European populations. 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Globally there was a strong relationship between effect size and SNPs predicted to be damaging (P=2.29x10-49); however, these variants which are most likely to impact on risk, are rare (MAF<5%).","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Glioma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Glioma","name":"Glioma","kind":"Disorder","source_path":"kb/disorders/Glioma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Glioma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Glioma.html#dataset-ega-egas00001001258"}],"context_names":["Glioma"],"disease_names":["Glioma"],"disease_name":"Glioma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Glioma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Glioma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Glioma.html#dataset-ega-egas00001001258"]},{"id":"dataset:ega:egas00001001259","accession":"ega:EGAS00001001259","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001001259","title":"WES sequencing of 100 human esophageal carcinoma cases","alternate_titles":[],"description":"WES sequencing of 100 human esophageal carcinoma cases","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Esophageal Carcinoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Esophageal_Carcinoma","name":"Esophageal Carcinoma","kind":"Disorder","source_path":"kb/disorders/Esophageal_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Esophageal_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Esophageal_Carcinoma.html#dataset-ega-egas00001001259"}],"context_names":["Esophageal Carcinoma"],"disease_names":["Esophageal Carcinoma"],"disease_name":"Esophageal Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Esophageal_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Esophageal_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Esophageal_Carcinoma.html#dataset-ega-egas00001001259"]},{"id":"dataset:ega:egas00001001268","accession":"ega:EGAS00001001268","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001001268","title":"Whole exome sequencing of papillary thyroid carcinoma in the Chinese population","alternate_titles":[],"description":"Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Here we submitted the sequencing results for PTC using 91 tumor-normal pairs through exome sequencing in the Chinese Han population.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Papillary Thyroid Carcinoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Papillary_Thyroid_Carcinoma","name":"Papillary Thyroid Carcinoma","kind":"Disorder","source_path":"kb/disorders/Papillary_Thyroid_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Papillary_Thyroid_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Papillary_Thyroid_Carcinoma.html#dataset-ega-egas00001001268"}],"context_names":["Papillary Thyroid Carcinoma"],"disease_names":["Papillary Thyroid Carcinoma"],"disease_name":"Papillary Thyroid Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Papillary_Thyroid_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Papillary_Thyroid_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Papillary_Thyroid_Carcinoma.html#dataset-ega-egas00001001268"]},{"id":"dataset:ega:egas00001001281","accession":"ega:EGAS00001001281","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001001281","title":"PLCG1 R707Q mutation is counter selected under targeted therapy in a patient with a hepatic angiosarcoma","alternate_titles":[],"description":"PLCG1 R707Q mutation is counter selected under targeted therapy in a patient with a hepatic angiosarcoma","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Angiosarcoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Angiosarcoma","name":"Angiosarcoma","kind":"Disorder","source_path":"kb/disorders/Angiosarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Angiosarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Angiosarcoma.html#dataset-ega-egas00001001281"}],"context_names":["Angiosarcoma"],"disease_names":["Angiosarcoma"],"disease_name":"Angiosarcoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Angiosarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Angiosarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Angiosarcoma.html#dataset-ega-egas00001001281"]},{"id":"dataset:ega:egas00001001291","accession":"ega:EGAS00001001291","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001001291","title":"Aim of project is to examine differences in the genome between basal cell carcinoma tumor and normal skin, and to better understand the types of mutations that occur as a tumor progresses from basaloid histology to more squamatized","alternate_titles":[],"description":"na","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Basal Cell Carcinoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Basal_Cell_Carcinoma","name":"Basal Cell Carcinoma","kind":"Disorder","source_path":"kb/disorders/Basal_Cell_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Basal_Cell_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Basal_Cell_Carcinoma.html#dataset-ega-egas00001001291"}],"context_names":["Basal Cell Carcinoma"],"disease_names":["Basal Cell Carcinoma"],"disease_name":"Basal Cell Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Basal_Cell_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Basal_Cell_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Basal_Cell_Carcinoma.html#dataset-ega-egas00001001291"]},{"id":"dataset:ega:egas00001001296","accession":"ega:EGAS00001001296","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001001296","title":"Integrated molecular analysis of adult T-cell leukemia/lymphoma","alternate_titles":[],"description":"This study is an integrated molecular study of adult T-cell leukemia/lymphoma which includes whole-exome (n = 81), whole-genome (n = 48), and transcriptome sequencing data (n = 57) as well as methylation (n = 109) and SNP array data (n = 426)","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Adult T-Cell Leukemia/Lymphoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Adult_T_Cell_Leukemia_Lymphoma","name":"Adult T-Cell Leukemia/Lymphoma","kind":"Disorder","source_path":"kb/disorders/Adult_T_Cell_Leukemia_Lymphoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Adult_T_Cell_Leukemia_Lymphoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Adult_T-Cell_Leukemia_Lymphoma.html#dataset-ega-egas00001001296"}],"context_names":["Adult T-Cell Leukemia/Lymphoma"],"disease_names":["Adult T-Cell Leukemia/Lymphoma"],"disease_name":"Adult T-Cell Leukemia/Lymphoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Adult_T_Cell_Leukemia_Lymphoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Adult_T_Cell_Leukemia_Lymphoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Adult_T-Cell_Leukemia_Lymphoma.html#dataset-ega-egas00001001296"]},{"id":"dataset:ega:egas00001001418","accession":"ega:EGAS00001001418","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001001418","title":"Exome Sequencing to Define the Landscape of Plasma Cells in Systemic Light chain Amyloidosis","alternate_titles":[],"description":"Systemic light chain amyloidosis (AL) is characterized by the deposition of immunoglobulin light chains as amyloid fibrils in different organs, where they form toxic protein aggregates. The underlying disease is a plasma cell disorder, but limited whole exome data are available. We report the findings of an exome sequencing study in AL to define a plasma cell signature and compare this to monoclonal gammopathy of undefined significance (MGUS) and myeloma (MM). Twenty-four samples from unselected newly diagnosed untreated AL patients were analysed. CD138+ cells were isolated from bone marrow cells using MACSorting (Miltenyi Biotech, Bisley, UK).","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Amyloidosis\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Amyloidosis","name":"Amyloidosis","kind":"Disorder","source_path":"kb/disorders/Amyloidosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Amyloidosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Amyloidosis.html#dataset-ega-egas00001001418"}],"context_names":["Amyloidosis"],"disease_names":["Amyloidosis"],"disease_name":"Amyloidosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Amyloidosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Amyloidosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Amyloidosis.html#dataset-ega-egas00001001418"]},{"id":"dataset:ega:egas00001001437","accession":"ega:EGAS00001001437","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001001437","title":"Chromatin immunoprecipitation linked to next-generation whole genome sequencing (ChIP-Seq) for H3K36me3 in paediatric high grade glioma cell lines KKNS4 and SF188 with and without a G34V mutation in H3F3A","alternate_titles":[],"description":"Glioblastomas of children and young adults have a median survival of only 12-15months and are clinically and biologically distinct from histologically similar cancers in older adults1. They are defined by highly specific mutations in the gene encoding the histone H3.3 variant H3F3A2, occurring either at or close to key residues marked by methylation for regulation of transcription – K27 and G34. We performed chromatin immunoprecipitation linked to next-generation whole genome sequencing (ChIP-Seq) for H3K36me3 in order to test the hypothesis that, rather than total H3K36me3, the G34V mutation may instead result in differential binding of the trimethyl mark throughout the genome.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Glioma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Glioma","name":"Glioma","kind":"Disorder","source_path":"kb/disorders/Glioma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Glioma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Glioma.html#dataset-ega-egas00001001437"}],"context_names":["Glioma"],"disease_names":["Glioma"],"disease_name":"Glioma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Glioma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Glioma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Glioma.html#dataset-ega-egas00001001437"]},{"id":"dataset:ega:egas00001001552","accession":"ega:EGAS00001001552","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001001552","title":"Whole genome sequencing of primary and metastatic Melanoma cases in an Australian cohort.","alternate_titles":[],"description":"Melanoma is the fourth most common cancer in Australia and the leading cause of cancer death in young adults. The Australian Melanoma Genome Project (AMGP) is analysing whole genomes from melanomas. We include the results of whole genome sequencing (WGS) for a number of datasets that include cutaneous, acral and mucosal melanoma subtypes.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:28467829"],"publication_contexts":[{"context_id":"disorder:Cutaneous_Melanoma","publication":"PMID:28467829"}],"publication":"PMID:28467829","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/28467829","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Metastatic Melanoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Cutaneous_Melanoma","name":"Cutaneous Melanoma","kind":"Disorder","source_path":"kb/disorders/Cutaneous_Melanoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cutaneous_Melanoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cutaneous_Melanoma.html#dataset-ega-egas00001001552"}],"context_names":["Cutaneous Melanoma"],"disease_names":["Cutaneous Melanoma"],"disease_name":"Cutaneous Melanoma","same_context_model_ids":["model:kb/disorders/Cutaneous_Melanoma.yaml:Xmrk-activated melanocytes in three-dimensional dermal collagen"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Cutaneous_Melanoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cutaneous_Melanoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cutaneous_Melanoma.html#dataset-ega-egas00001001552"]},{"id":"dataset:ega:egas00001001563","accession":"ega:EGAS00001001563","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001001563","title":"Genomic characterization of Malignant Pleural Mesothelioma.","alternate_titles":[],"description":"Genomic characterization of Malignant Pleural Mesothelioma using RNA-seq, Exome and Illumina 2.5 M array.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Mesothelioma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Malignant_Mesothelioma","name":"Malignant Mesothelioma","kind":"Disorder","source_path":"kb/disorders/Malignant_Mesothelioma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Malignant_Mesothelioma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Malignant_Mesothelioma.html#dataset-ega-egas00001001563"}],"context_names":["Malignant Mesothelioma"],"disease_names":["Malignant Mesothelioma"],"disease_name":"Malignant Mesothelioma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Malignant_Mesothelioma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Malignant_Mesothelioma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Malignant_Mesothelioma.html#dataset-ega-egas00001001563"]},{"id":"dataset:ega:egas00001001653","accession":"ega:EGAS00001001653","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001001653","title":"Whole-Genome and Epigenomic Landscapes of Etiologically Distinct Subtypes of Cholangiocarcinoma","alternate_titles":[],"description":"Cholangiocarcinoma (CCA) is a hepatobiliary malignancy exhibiting high incidence in countries with endemic liver-fluke infection. We analyzed 489 CCAs from 10 countries, combining whole-genome (71 cases), targeted/exome, copy-number, gene expression, and DNA methylation information. Integrative clustering defined 4 CCA clusters-fluke-positive CCAs (clusters 1/2) are enriched in ERBB2 amplifications and TP53 mutations; conversely, fluke-negative CCAs (clusters 3/4) exhibit high copy-number alterations and PD-1/PD-L2 expression, or epigenetic mutations (IDH1/2, BAP1) and FGFR/PRKA-related gene rearrangements.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:28667006"],"publication_contexts":[{"context_id":"disorder:Cholangiocarcinoma","publication":"PMID:28667006"}],"publication":"PMID:28667006","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/28667006","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Cholangiocarcinoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Cholangiocarcinoma","name":"Cholangiocarcinoma","kind":"Disorder","source_path":"kb/disorders/Cholangiocarcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cholangiocarcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cholangiocarcinoma.html#dataset-ega-egas00001001653"}],"context_names":["Cholangiocarcinoma"],"disease_names":["Cholangiocarcinoma"],"disease_name":"Cholangiocarcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cholangiocarcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cholangiocarcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cholangiocarcinoma.html#dataset-ega-egas00001001653"]},{"id":"dataset:ega:egas00001001657","accession":"ega:EGAS00001001657","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001001657","title":"Exome sequencing of retinoblastoma tumors","alternate_titles":[],"description":"Retinoblastoma is the most common intraocular cancer of infancy and childhood, with an incidence of one case per 15,000 - 20,000 live births. Patients in developed countries have a good prognosis. However, in most cases, enucleation of the affected eye is required. In low- and middle-income countries, retinoblastoma is frequently lethal. A loss of function of both alleles of the RB1 gene is an early event in the development of retinoblastoma. However, other genes are also likely to be involved in the development of this cancer.","alternate_descriptions":[],"data_types":["WES"],"data_type_labels":["Whole exome sequencing"],"data_type_label":"Whole exome sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Retinoblastoma\"); description-level mentions were not accepted. EGA study_type: Exome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Retinoblastoma","name":"Retinoblastoma","kind":"Disorder","source_path":"kb/disorders/Retinoblastoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Retinoblastoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Retinoblastoma.html#dataset-ega-egas00001001657"}],"context_names":["Retinoblastoma"],"disease_names":["Retinoblastoma"],"disease_name":"Retinoblastoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Retinoblastoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Retinoblastoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Retinoblastoma.html#dataset-ega-egas00001001657"]},{"id":"dataset:ega:egas00001001661","accession":"ega:EGAS00001001661","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001001661","title":"Transcriptome Sequencing (RNAseq) enables utilization of Formalin-Fixed, Paraffin-Embedded Biopsies with Clear Cell Renal Cell Carcinoma for Exploration of Disease Biology and Biomarker Development","alternate_titles":[],"description":"Formalin-fixed, paraffin-embedded (FFPE) tissues are an underused resource for molecular analyses. This proof of concept study aimed to compare RNAseq results from FFPE biopsies with the corresponding RNAlater® (Qiagen, Germany) stored samples from clear cell renal cell carcinoma (ccRCC) patients to investigate feasibility of RNAseq in archival tissue. From each of 16 patients undergoing partial or full nephrectomy, four core biopsies, such as two specimens with ccRCC and two specimens of adjacent normal tissue, were obtained with a 16g needle. One normal and one ccRCC tissue specimen per patient was stored either in FFPE or RNAlater®.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Clear Cell Renal Cell Carcinoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Clear_Cell_Renal_Cell_Carcinoma","name":"Clear Cell Renal Cell Carcinoma","kind":"Disorder","source_path":"kb/disorders/Clear_Cell_Renal_Cell_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Clear_Cell_Renal_Cell_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Clear_Cell_Renal_Cell_Carcinoma.html#dataset-ega-egas00001001661"}],"context_names":["Clear Cell Renal Cell Carcinoma"],"disease_names":["Clear Cell Renal Cell Carcinoma"],"disease_name":"Clear Cell Renal Cell Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Clear_Cell_Renal_Cell_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Clear_Cell_Renal_Cell_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Clear_Cell_Renal_Cell_Carcinoma.html#dataset-ega-egas00001001661"]},{"id":"dataset:ega:egas00001001709","accession":"ega:EGAS00001001709","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001001709","title":"Histological Transformation and Progression in Follicular Lymphoma: a Clonal Evolution Study","alternate_titles":[],"description":"Background: Follicular lymphoma (FL) is an indolent, yet incurable B-cell malignancy. A subset of patients experience increased mortality rate driven by two distinct clinical end points: histological transformation and early progression after immuno-chemotherapy. The nature of tumor clonal dynamics leading to these clinical endpoints is poorly understood and previously determined genetic alterations do not explain the majority of transformed cases or accurately predict early progressive disease.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Follicular Lymphoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Follicular_Lymphoma","name":"Follicular Lymphoma","kind":"Disorder","source_path":"kb/disorders/Follicular_Lymphoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Follicular_Lymphoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Follicular_Lymphoma.html#dataset-ega-egas00001001709"}],"context_names":["Follicular Lymphoma"],"disease_names":["Follicular Lymphoma"],"disease_name":"Follicular Lymphoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Follicular_Lymphoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Follicular_Lymphoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Follicular_Lymphoma.html#dataset-ega-egas00001001709"]},{"id":"dataset:ega:egas00001001741","accession":"ega:EGAS00001001741","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001001741","title":"Searching for variants associated with endometriosis","alternate_titles":[],"description":"We explored regulatory mechanism of a SNP on chromosome 9p21 associated with endometriosis by leveraging “allele-specific” functional genomic approaches. By re-sequencing 1.29 Mb of 9p21 region and scrutinizing DNase-seq data from the ENCODE project, we prioritized rs17761446 as a candidate functional variant that was in perfect linkage disequilibrium with the original GWAS SNP (rs10965235) and located on DNase I hypersensitive site. Chromosome conformation capture followed by high-throughput sequencing revealed that the protective G allele of rs17761446 exerted stronger chromatin interaction with ANRIL promoter.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:27055116"],"publication_contexts":[{"context_id":"disorder:Endometriosis","publication":"PMID:27055116"}],"publication":"PMID:27055116","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/27055116","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Endometriosis\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Endometriosis","name":"Endometriosis","kind":"Disorder","source_path":"kb/disorders/Endometriosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Endometriosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Endometriosis.html#dataset-ega-egas00001001741"}],"context_names":["Endometriosis"],"disease_names":["Endometriosis"],"disease_name":"Endometriosis","same_context_model_ids":["model:kb/disorders/Endometriosis.yaml:Droplet-based microfluidic protease-activity profiling platform (PrAMA; MIT Griffith/Han)"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Endometriosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Endometriosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Endometriosis.html#dataset-ega-egas00001001741"]},{"id":"dataset:ega:egas00001001821","accession":"ega:EGAS00001001821","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001001821","title":"Epigenome and transcriptome profiling of chronic lymphocytic leukemia patients","alternate_titles":[],"description":"Chronic lymphocytic leukemia (CLL) is characterized by substantial clinical heterogeneity, despite relatively few genetic alterations. To provide a basis for studying epigenome deregulation in CLL, we established genome-wide chromatin accessibility maps for 88 CLL samples from 55 patients using the ATAC-seq assay, and we also performed ChIPmentation and RNA-seq profiling for ten representative samples. Based on the resulting dataset, we devised and applied a bioinformatic method that links chromatin profiles to clinical annotations. Our analysis identified sample-specific variation on top of a shared core of CLL regulatory regions.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:27346425"],"publication_contexts":[{"context_id":"disorder:Chronic_Lymphocytic_Leukemia","publication":"PMID:27346425"}],"publication":"PMID:27346425","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/27346425","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Chronic Lymphocytic Leukemia\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Chronic_Lymphocytic_Leukemia","name":"Chronic Lymphocytic Leukemia","kind":"Disorder","source_path":"kb/disorders/Chronic_Lymphocytic_Leukemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Lymphocytic_Leukemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chronic_Lymphocytic_Leukemia.html#dataset-ega-egas00001001821"}],"context_names":["Chronic Lymphocytic Leukemia"],"disease_names":["Chronic Lymphocytic Leukemia"],"disease_name":"Chronic Lymphocytic Leukemia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chronic_Lymphocytic_Leukemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Lymphocytic_Leukemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chronic_Lymphocytic_Leukemia.html#dataset-ega-egas00001001821"]},{"id":"dataset:ega:egas00001001849","accession":"ega:EGAS00001001849","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001001849","title":"Whole-genome sequencing of two probands with hereditary spastic paraplegia reveals novel splice-donor region mutation and known pathogenic mutation in SPG11","alternate_titles":[],"description":"Hereditary spastic paraplegias (SPG) are a group of heterogeneous neurodegenerative disorders, which are often presented with overlapping phenotypes such as progressive paraparesis and spasticity. To assist the diagnosis of SPG subtypes, next-generation sequencing is often used to provide supporting evidence. In this study, we report the case of two probands from the same family with SPG symptoms, including bilateral lower limbs weakness, unsteady gait, cognitive decline, dysarthria and slurring of speech since age of 14.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Hereditary Spastic Paraplegia\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Hereditary_Spastic_Paraplegia","name":"Hereditary Spastic Paraplegia","kind":"Disorder","source_path":"kb/disorders/Hereditary_Spastic_Paraplegia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hereditary_Spastic_Paraplegia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hereditary_Spastic_Paraplegia.html#dataset-ega-egas00001001849"}],"context_names":["Hereditary Spastic Paraplegia"],"disease_names":["Hereditary Spastic Paraplegia"],"disease_name":"Hereditary Spastic Paraplegia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hereditary_Spastic_Paraplegia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hereditary_Spastic_Paraplegia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hereditary_Spastic_Paraplegia.html#dataset-ega-egas00001001849"]},{"id":"dataset:ega:egas00001001892","accession":"ega:EGAS00001001892","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001001892","title":"Inactivation of TGFβ receptors in stem cells drives cutaneous squamous cell carcinoma - 30 whole exomes","alternate_titles":[],"description":"Melanoma patients treated with oncogenic BRAF inhibitors can develop cutaneous squamous cell carcinoma (cSCC) within weeks of treatment, driven by paradoxical RAS/RAF/MAPK pathway activation. Here, we identify frequent TGFBR1 and TGFBR2 mutations in human vemurafenib-induced skin lesions and in sporadic cSCC. Functional analysis reveals these mutations ablate canonical TGFβ Smad signaling which is localised to bulge stem cells in both normal human and murine skin. MAPK pathway hyperactivation (through BrafV600E or KrasG12D knockin) and TGFβ signaling ablation (through Tgfbr1 deletion) in LGR5+ve stem cells enables rapid cSCC development in the mouse.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Cutaneous Squamous Cell Carcinoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Cutaneous_Squamous_Cell_Carcinoma","name":"Cutaneous Squamous Cell Carcinoma","kind":"Disorder","source_path":"kb/disorders/Cutaneous_Squamous_Cell_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cutaneous_Squamous_Cell_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cutaneous_Squamous_Cell_Carcinoma.html#dataset-ega-egas00001001892"}],"context_names":["Cutaneous Squamous Cell Carcinoma"],"disease_names":["Cutaneous Squamous Cell Carcinoma"],"disease_name":"Cutaneous Squamous Cell Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cutaneous_Squamous_Cell_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cutaneous_Squamous_Cell_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cutaneous_Squamous_Cell_Carcinoma.html#dataset-ega-egas00001001892"]},{"id":"dataset:ega:egas00001001943","accession":"ega:EGAS00001001943","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001001943","title":"Histone Acetylome-wide Association Study of Autism Spectrum Disorder","alternate_titles":[],"description":"H3K27ac ChIP-seq were performed on postmortem samples from autism spectrum disorder and matched control brains. Tissues were chosen from three brain regions: prefrontal cortex, temporal cortex and cerebellum.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Autism Spectrum Disorder\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Autism_Spectrum_Disorder","name":"Autism Spectrum Disorder","kind":"Disorder","source_path":"kb/disorders/Autism_Spectrum_Disorder.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autism_Spectrum_Disorder.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autism_Spectrum_Disorder.html#dataset-ega-egas00001001943"}],"context_names":["Autism Spectrum Disorder"],"disease_names":["Autism Spectrum Disorder"],"disease_name":"Autism Spectrum Disorder","same_context_model_ids":["model:kb/disorders/Autism_Spectrum_Disorder.yaml:Genotype-defined patient iPSC-derived neuronal networks","model:kb/disorders/Autism_Spectrum_Disorder.yaml:Multi-genotype human cortical organoid and neural-progenitor panel"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Autism_Spectrum_Disorder.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autism_Spectrum_Disorder.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Autism_Spectrum_Disorder.html#dataset-ega-egas00001001943"]},{"id":"dataset:ega:egas00001001960","accession":"ega:EGAS00001001960","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001001960","title":"Novel CNV contribution to schizophrenia from a genome wide study of 41,321 subjects","alternate_titles":[],"description":"Genomic copy number variants (CNVs) have been strongly implicated in the etiology schizophrenia (SCZ). However, apart from a small number of risk variants, elucidation of the CNV contribution to risk has been difficult due to the very low frequencies of risk alleles, all occurring in less than 1% of patients. We sought to address this obstacle through a collaborative effort unprecedented in psychiatry in which we applied a centralized analysis pipeline to a large SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden is observed in SCZ patients (OR=1.11, P=5.7e-15), and persists after excluding loci implicated in previous studies (OR=1.07, P=1.7e-6).","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:9820031"],"publication_contexts":[{"context_id":"disorder:Schizophrenia","publication":"PMID:9820031"}],"publication":"PMID:9820031","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/9820031","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Schizophrenia\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Schizophrenia","name":"Schizophrenia","kind":"Disorder","source_path":"kb/disorders/Schizophrenia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Schizophrenia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Schizophrenia.html#dataset-ega-egas00001001960"}],"context_names":["Schizophrenia"],"disease_names":["Schizophrenia"],"disease_name":"Schizophrenia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Schizophrenia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Schizophrenia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Schizophrenia.html#dataset-ega-egas00001001960"]},{"id":"dataset:ega:egas00001002006","accession":"ega:EGAS00001002006","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002006","title":"HipSci HumanExome BeadChip analysis - Hereditary Spastic Paraplegia","alternate_titles":[],"description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Genotyping analysis using the Infinium HumanExome BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Hereditary Spastic Paraplegia.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Hereditary Spastic Paraplegia\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Hereditary_Spastic_Paraplegia","name":"Hereditary Spastic Paraplegia","kind":"Disorder","source_path":"kb/disorders/Hereditary_Spastic_Paraplegia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hereditary_Spastic_Paraplegia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hereditary_Spastic_Paraplegia.html#dataset-ega-egas00001002006"}],"context_names":["Hereditary Spastic Paraplegia"],"disease_names":["Hereditary Spastic Paraplegia"],"disease_name":"Hereditary Spastic Paraplegia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hereditary_Spastic_Paraplegia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hereditary_Spastic_Paraplegia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hereditary_Spastic_Paraplegia.html#dataset-ega-egas00001002006"]},{"id":"dataset:ega:egas00001002009","accession":"ega:EGAS00001002009","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002009","title":"HipSci HumanExome BeadChip analysis - Alport Syndrome","alternate_titles":[],"description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Genotyping analysis using the Infinium HumanExome BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Alport Syndrome.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Alport Syndrome\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Alport_Syndrome","name":"Alport Syndrome","kind":"Disorder","source_path":"kb/disorders/Alport_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alport_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Alport_Syndrome.html#dataset-ega-egas00001002009"}],"context_names":["Alport Syndrome"],"disease_names":["Alport Syndrome"],"disease_name":"Alport Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Alport_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alport_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Alport_Syndrome.html#dataset-ega-egas00001002009"]},{"id":"dataset:ega:egas00001002019","accession":"ega:EGAS00001002019","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002019","title":"HipSci HumanExome BeadChip analysis - Alport syndrome (Manchester)","alternate_titles":[],"description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Genotyping analysis using the Infinium HumanExome BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Alport syndrome (Manchester Uni).","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Alport Syndrome\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Alport_Syndrome","name":"Alport Syndrome","kind":"Disorder","source_path":"kb/disorders/Alport_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alport_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Alport_Syndrome.html#dataset-ega-egas00001002019"}],"context_names":["Alport Syndrome"],"disease_names":["Alport Syndrome"],"disease_name":"Alport Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Alport_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alport_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Alport_Syndrome.html#dataset-ega-egas00001002019"]},{"id":"dataset:ega:egas00001002024","accession":"ega:EGAS00001002024","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002024","title":"HipSci HumanHT 12 Expression BeadChip analysis - Alport syndrome","alternate_titles":[],"description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Expression analysis using the Illumina HumanHT -12 Expression BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Alport syndrome.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Alport Syndrome\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Alport_Syndrome","name":"Alport Syndrome","kind":"Disorder","source_path":"kb/disorders/Alport_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alport_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Alport_Syndrome.html#dataset-ega-egas00001002024"}],"context_names":["Alport Syndrome"],"disease_names":["Alport Syndrome"],"disease_name":"Alport Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Alport_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alport_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Alport_Syndrome.html#dataset-ega-egas00001002024"]},{"id":"dataset:ega:egas00001002149","accession":"ega:EGAS00001002149","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002149","title":"RNA-sequencing of six Pilocytic astrocytoma tumors","alternate_titles":[],"description":"Pilocytic astrocytoma (PA) is the most common pediatric brain tumor. A recurrent feature of PA is deregulation of the mitogen activated protein kinase (MAPK) pathway most often through KIAA1549-BRAF fusion, but also by other BRAF- or RAF1-gene fusions and point mutations (e.g. BRAFV600E). These features may serve as diagnostic and prognostic markers, and also facilitate development of targeted therapy. The aim of this study was to characterize the genetic alterations underlying the development of PA tumor in six cases, and evaluate methods for fusion oncogene detection.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:28448514"],"publication_contexts":[{"context_id":"disorder:Pilocytic_Astrocytoma","publication":"PMID:28448514"}],"publication":"PMID:28448514","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/28448514","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Pilocytic Astrocytoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Pilocytic_Astrocytoma","name":"Pilocytic Astrocytoma","kind":"Disorder","source_path":"kb/disorders/Pilocytic_Astrocytoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pilocytic_Astrocytoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pilocytic_Astrocytoma.html#dataset-ega-egas00001002149"}],"context_names":["Pilocytic Astrocytoma"],"disease_names":["Pilocytic Astrocytoma"],"disease_name":"Pilocytic Astrocytoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Pilocytic_Astrocytoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pilocytic_Astrocytoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Pilocytic_Astrocytoma.html#dataset-ega-egas00001002149"]},{"id":"dataset:ega:egas00001002161","accession":"ega:EGAS00001002161","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002161","title":"Methylation of Ewing sarcoma tumors (ICGC)","alternate_titles":[],"description":"Ewing sarcoma (ES) is a primary bone tumor initiated by an EWSR1-ETS gene fusion. To characterize the methylation of Ewing sarcoma, reduced representation bisulfite sequencing was performed.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:28134926"],"publication_contexts":[{"context_id":"disorder:Ewing_Sarcoma","publication":"PMID:28134926"}],"publication":"PMID:28134926","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/28134926","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Ewing Sarcoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Ewing_Sarcoma","name":"Ewing Sarcoma","kind":"Disorder","source_path":"kb/disorders/Ewing_Sarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ewing_Sarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#dataset-ega-egas00001002161"}],"context_names":["Ewing Sarcoma"],"disease_names":["Ewing Sarcoma"],"disease_name":"Ewing Sarcoma","same_context_model_ids":["model:kb/disorders/Ewing_Sarcoma.yaml:BARD1-variant PSaRC318 and BARD1-depleted Ewing cells","model:kb/disorders/Ewing_Sarcoma.yaml:Ewing sarcoma tumor organoid model systems","model:kb/disorders/Ewing_Sarcoma.yaml:Flow-perfusion Ewing sarcoma 3D scaffold coculture","model:kb/disorders/Ewing_Sarcoma.yaml:Human embryonic mesenchymal stem cell EWS-FLI1 transformation model","model:kb/disorders/Ewing_Sarcoma.yaml:Patient-derived Ewing sarcoma culture panel"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Ewing_Sarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ewing_Sarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#dataset-ega-egas00001002161"]},{"id":"dataset:ega:egas00001002183","accession":"ega:EGAS00001002183","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002183","title":"Pediatric Non-Down Syndrome Acute Megakaryoblastic Leukemia is Characterized by Distinct Genomic Subsets with Varying Outcomes","alternate_titles":[],"description":"Acute Megakaryoblastic Leukemia (AMKL) is a subtype of acute myeloid leukemia (AML) in which cells morphologically resemble abnormal megakaryoblasts. While extremely rare in adults, AMKL accounts for 4-15% of newly diagnosed childhood AML1-3. A significant proportion of pediatric AMKL cases occur in children with Down syndrome (DS). These patients have excellent outcomes and are characterized at the genomic level by a founding GATA1 mutation4-6. In contrast, AMKL in patients without DS (non-DS-AMKL) is frequently associated with poor outcomes.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Acute Megakaryoblastic Leukemia\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Acute_Megakaryoblastic_Leukemia","name":"Acute Megakaryoblastic Leukemia","kind":"Disorder","source_path":"kb/disorders/Acute_Megakaryoblastic_Leukemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Acute_Megakaryoblastic_Leukemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Acute_Megakaryoblastic_Leukemia.html#dataset-ega-egas00001002183"}],"context_names":["Acute Megakaryoblastic Leukemia"],"disease_names":["Acute Megakaryoblastic Leukemia"],"disease_name":"Acute Megakaryoblastic Leukemia","same_context_model_ids":["model:kb/disorders/Acute_Megakaryoblastic_Leukemia.yaml:CBFA2T3-GLIS2 Cord-Blood HSPC Endothelial Coculture","model:kb/disorders/Acute_Megakaryoblastic_Leukemia.yaml:NUP98-KDM5A Cord-Blood HSPC Model","model:kb/disorders/Acute_Megakaryoblastic_Leukemia.yaml:Trisomy-21 GATA1/STAG2 Double-Mutant iPSC Model"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Acute_Megakaryoblastic_Leukemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Acute_Megakaryoblastic_Leukemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Acute_Megakaryoblastic_Leukemia.html#dataset-ega-egas00001002183"]},{"id":"dataset:ega:egas00001002198","accession":"ega:EGAS00001002198","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002198","title":"The genomic landscape of Burkitt Lymphoma","alternate_titles":[],"description":"As part of the ICGC, the ICGC MMML-Seq project performed whole genome sequencing and RNA sequencing of Burkitt Lymphomas . Burkitt lymphomas are the most common B-cell lymphomas in childhood. Analyses were performed in concordance with the guidelines of the ICGC. The results define the genomic landscape of structural variants, somatic single nucleotide variants and mutational signatures in these lymphomas.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Burkitt Lymphoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Burkitt_Lymphoma","name":"Burkitt Lymphoma","kind":"Disorder","source_path":"kb/disorders/Burkitt_Lymphoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Burkitt_Lymphoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Burkitt_Lymphoma.html#dataset-ega-egas00001002198"}],"context_names":["Burkitt Lymphoma"],"disease_names":["Burkitt Lymphoma"],"disease_name":"Burkitt Lymphoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Burkitt_Lymphoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Burkitt_Lymphoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Burkitt_Lymphoma.html#dataset-ega-egas00001002198"]},{"id":"dataset:ega:egas00001002199","accession":"ega:EGAS00001002199","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002199","title":"The genomic landscape of follicular and diffuse large B-cell lymphoma","alternate_titles":[],"description":"As part of the ICGC, the ICGC MMML-Seq project performed whole genome sequencing and RNA sequencing of follicular and diffuse large B-cell lymphoma. Follicular and diffuse large B-cell lymphomas are the most common B-cell lymphomas in adulthood. Analyses were performed in concordance with the guidelines of the ICGC. The results define the genomic landscape of structural variants, somatic single nucleotide variants and mutational signatures in these lymphomas","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Diffuse Large B-Cell Lymphoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Diffuse_Large_B_Cell_Lymphoma","name":"Diffuse Large B-Cell Lymphoma","kind":"Disorder","source_path":"kb/disorders/Diffuse_Large_B_Cell_Lymphoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Diffuse_Large_B_Cell_Lymphoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Diffuse_Large_B-Cell_Lymphoma.html#dataset-ega-egas00001002199"}],"context_names":["Diffuse Large B-Cell Lymphoma"],"disease_names":["Diffuse Large B-Cell Lymphoma"],"disease_name":"Diffuse Large B-Cell Lymphoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Diffuse_Large_B_Cell_Lymphoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Diffuse_Large_B_Cell_Lymphoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Diffuse_Large_B-Cell_Lymphoma.html#dataset-ega-egas00001002199"]},{"id":"dataset:ega:egas00001002230","accession":"ega:EGAS00001002230","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002230","title":"Whole genome bisulfite sequencing of hepatitis B virus-associated hepatocellular carcinoma tumor and non-cancerous samples","alternate_titles":[],"description":"To understand comprehensive epigenetic alterations in hepatitis B virus-associated HCC, we have conducted a whole genome bisulfite sequencing of 5 tumor samples and 3 non-cancerous samples (3 pairs and 2 tumors).","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Hepatitis B\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Hepatitis_B","name":"Hepatitis B","kind":"Disorder","source_path":"kb/disorders/Hepatitis_B.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatitis_B.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hepatitis_B.html#dataset-ega-egas00001002230"}],"context_names":["Hepatitis B"],"disease_names":["Hepatitis B"],"disease_name":"Hepatitis B","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hepatitis_B.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatitis_B.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hepatitis_B.html#dataset-ega-egas00001002230"]},{"id":"dataset:ega:egas00001002276","accession":"ega:EGAS00001002276","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002276","title":"GWAS data (Illumina 2.5 M SNPs) in Cuban cohorts of dengue disease","alternate_titles":[],"description":"We will have 274 individuals typed for the Illumina Human Omni 2.5 chip. The individuals are from two locations in Cuba (Havana and Guantanamo) and from four phenotype classes (asymptomatic, control dengue fever and dengue hemorrhagic fever).","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:28241052"],"publication_contexts":[{"context_id":"disorder:Dengue","publication":"PMID:28241052"}],"publication":"PMID:28241052","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/28241052","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Dengue\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Dengue","name":"Dengue","kind":"Disorder","source_path":"kb/disorders/Dengue.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dengue.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Dengue.html#dataset-ega-egas00001002276"}],"context_names":["Dengue"],"disease_names":["Dengue"],"disease_name":"Dengue","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Dengue.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dengue.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Dengue.html#dataset-ega-egas00001002276"]},{"id":"dataset:ega:egas00001002299","accession":"ega:EGAS00001002299","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002299","title":"Mesothelioma Genomics Study - WGS tumour/normal pairs","alternate_titles":[],"description":"Malignant mesothelioma (MM) is an incurable and aggressive tumour that occurs principally in the pleura as a consequence of inhaling asbestos fibres. There are >15,000 cases per annum worldwide, the incidence is increasing and Australia has one of the world's highest incidence rates. Surgery, chemotherapy and radiotherapy (or their combinations) all feature in the clinical management but do not impact significantly on overall survival. This study uses whole genome sequencing (WGS) with the aim of identifying mesothelioma-related genomic alterations and potentially identifying novel treatment strategies.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Mesothelioma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Malignant_Mesothelioma","name":"Malignant Mesothelioma","kind":"Disorder","source_path":"kb/disorders/Malignant_Mesothelioma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Malignant_Mesothelioma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Malignant_Mesothelioma.html#dataset-ega-egas00001002299"}],"context_names":["Malignant Mesothelioma"],"disease_names":["Malignant Mesothelioma"],"disease_name":"Malignant Mesothelioma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Malignant_Mesothelioma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Malignant_Mesothelioma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Malignant_Mesothelioma.html#dataset-ega-egas00001002299"]},{"id":"dataset:ega:egas00001002324","accession":"ega:EGAS00001002324","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002324","title":"Genome-to-genome analysis highlights the impact of the human innate and adaptive immune systems on the hepatitis C virus","alternate_titles":[],"description":"Outcomes of hepatitis C virus (HCV) infection and treatment depend on viral and host genetic factors. We use human genome-wide genotyping arrays and new whole-genome HCV viral sequencing technologies to perform a systematic genome-to-genome study of 542 individuals chronically infected with HCV, predominately genotype 3. We show that both HLA alleles and interferon lambda innate immune system genes drive viral genome polymorphism, and that IFNL4 genotypes determine HCV viral load through a mechanism that is dependent on a specific polymorphism in the HCV polyprotein. We highlight the interplay between innate immune responses and the viral genome in HCV control.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:28394351"],"publication_contexts":[{"context_id":"disorder:Hepatitis_C","publication":"PMID:28394351"}],"publication":"PMID:28394351","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/28394351","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Hepatitis C\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Hepatitis_C","name":"Hepatitis C","kind":"Disorder","source_path":"kb/disorders/Hepatitis_C.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatitis_C.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hepatitis_C.html#dataset-ega-egas00001002324"}],"context_names":["Hepatitis C"],"disease_names":["Hepatitis C"],"disease_name":"Hepatitis C","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hepatitis_C.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatitis_C.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hepatitis_C.html#dataset-ega-egas00001002324"]},{"id":"dataset:ega:egas00001002334","accession":"ega:EGAS00001002334","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002334","title":"A GWAS in uveal melanoma identifies risk polymorphisms in the CLPTM1L locus.","alternate_titles":[],"description":"Uveal melanoma, a rare malignant tumor of the eye, is predominantly observed in populations of European ancestry. A genome-wide association study of 259 uveal melanoma patients compared to 401 controls all of European ancestry revealed a candidate locus at chromosome 5p15.33 (region rs421284: OR = 1.7, CI 1.43-2.05). This locus was replicated in an independent set of 276 cases and 184 controls. In addition, risk variants from this region were positively associated with higher expression of CLPTM1L. In conclusion, the CLPTM1L region contains risk alleles for uveal melanoma susceptibility, suggesting that CLPTM1L could play a role in uveal melanoma oncogenesis.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:28781888"],"publication_contexts":[{"context_id":"disorder:Uveal_Melanoma","publication":"PMID:28781888"}],"publication":"PMID:28781888","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/28781888","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Uveal Melanoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Uveal_Melanoma","name":"Uveal Melanoma","kind":"Disorder","source_path":"kb/disorders/Uveal_Melanoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Uveal_Melanoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Uveal_Melanoma.html#dataset-ega-egas00001002334"}],"context_names":["Uveal Melanoma"],"disease_names":["Uveal Melanoma"],"disease_name":"Uveal Melanoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Uveal_Melanoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Uveal_Melanoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Uveal_Melanoma.html#dataset-ega-egas00001002334"]},{"id":"dataset:ega:egas00001002344","accession":"ega:EGAS00001002344","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002344","title":"Whole-Genome Sequencing Suggests Schizophrenia Risk Mechanisms in Humans with 22q11.2 Deletion Syndrome","alternate_titles":[],"description":"Chromosome 22q11.2 microdeletions impart a high but incomplete risk for schizophrenia. Possible mechanisms include genome-wide effects of DGCR8 haploinsufficiency. In a proof-of-principle study to assess the power of this model, we used high-quality, whole-genome sequencing of nine individuals with 22q11.2 deletions and extreme phenotypes (schizophrenia, or no psychotic disorder at age >50 years). The schizophrenia group had a greater burden of rare, damaging variants impacting protein-coding neurofunctional genes, including genes involved in neuron projection (nominal P = 0.02, joint burden of three variant types). Variants in the intact 22q11.2 region were not major contributors.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:26384369"],"publication_contexts":[{"context_id":"disorder:22q11.2_Deletion_Syndrome","publication":"PMID:26384369"}],"publication":"PMID:26384369","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/26384369","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"22q11.2 Deletion Syndrome\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:22q11.2_Deletion_Syndrome","name":"22q11.2 Deletion Syndrome","kind":"Disorder","source_path":"kb/disorders/22q11.2_Deletion_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/22q11.2_Deletion_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/22q11.2_Deletion_Syndrome.html#dataset-ega-egas00001002344"}],"context_names":["22q11.2 Deletion Syndrome"],"disease_names":["22q11.2 Deletion Syndrome"],"disease_name":"22q11.2 Deletion Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/22q11.2_Deletion_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/22q11.2_Deletion_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/22q11.2_Deletion_Syndrome.html#dataset-ega-egas00001002344"]},{"id":"dataset:ega:egas00001002365","accession":"ega:EGAS00001002365","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002365","title":"A GWAS in uveal melanoma identifies risk polymorphisms in the CLPTM1L locus.","alternate_titles":[],"description":"Uveal melanoma, a rare malignant tumor of the eye, is predominantly observed in populations of European ancestry. A genome-wide association study of 259 uveal melanoma patients compared to 401 controls all of European ancestry revealed a candidate locus at chromosome 5p15.33 (region rs421284: OR = 1.7, CI 1.43-2.05). This locus was replicated in an independent set of 276 cases and 184 controls. In addition, risk variants from this region were positively associated with higher expression of CLPTM1L. In conclusion, the CLPTM1L region contains risk alleles for uveal melanoma susceptibility, suggesting that CLPTM1L could play a role in uveal melanoma oncogenesis.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Uveal Melanoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Uveal_Melanoma","name":"Uveal Melanoma","kind":"Disorder","source_path":"kb/disorders/Uveal_Melanoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Uveal_Melanoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Uveal_Melanoma.html#dataset-ega-egas00001002365"}],"context_names":["Uveal Melanoma"],"disease_names":["Uveal Melanoma"],"disease_name":"Uveal Melanoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Uveal_Melanoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Uveal_Melanoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Uveal_Melanoma.html#dataset-ega-egas00001002365"]},{"id":"dataset:ega:egas00001002401","accession":"ega:EGAS00001002401","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002401","title":"Cell of origin-specific genetic alterations and chromosomal instability have therapeutic and immunologic impact in diffuse large B-cell lymphoma","alternate_titles":[],"description":"Diffuse large B-cell lymphoma (DLBCL), the most common lymphoma subtype worldwide, is a diverse disease with distinct molecular and clinical features in which ~40% of patients experience treatment failure. To understand the molecular distinctions and their therapeutic relevance specific to Cell-of-Origin (COO) in DLBCL, for the first time we performed an integrative genomic and transcriptomic analysis of biopsies from a large population registry-based cohort of uniformly treated patients with de novo DLBCL. We identified that NFATC1 amplification was significantly enriched in ABC-DLBCL with prognostic significance.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Diffuse Large B-Cell Lymphoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Diffuse_Large_B_Cell_Lymphoma","name":"Diffuse Large B-Cell Lymphoma","kind":"Disorder","source_path":"kb/disorders/Diffuse_Large_B_Cell_Lymphoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Diffuse_Large_B_Cell_Lymphoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Diffuse_Large_B-Cell_Lymphoma.html#dataset-ega-egas00001002401"}],"context_names":["Diffuse Large B-Cell Lymphoma"],"disease_names":["Diffuse Large B-Cell Lymphoma"],"disease_name":"Diffuse Large B-Cell Lymphoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Diffuse_Large_B_Cell_Lymphoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Diffuse_Large_B_Cell_Lymphoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Diffuse_Large_B-Cell_Lymphoma.html#dataset-ega-egas00001002401"]},{"id":"dataset:ega:egas00001002437","accession":"ega:EGAS00001002437","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002437","title":"Integrative genomic and transcriptomic analysis of adult leiomyosarcoma (HIPO-028, HIPO-018, HIPO-021)","alternate_titles":[],"description":"Leiomyosarcoma (LMS) is an aggressive mesenchmyal malignancy with few therapeutic options. The mechanisms underlying LMS development, including clinically actionable genetic vulnerabilities, are largely unknown. We performed genomic and transcriptomic profiling of a large cohort of LMS tumors and identified substantial mutational heterogeneity, near-universal inactivation of TP53 and RB1, widespread DNA copy number alterations, chromothripsis, and frequent whole-genome duplication. Furthermore, we discovered recurrent alterations in telomere maintenance genes such as ATRX, RBL2, and RPA1, resulting in alternative lengthening of telomeres in 78% of cases.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:5762758"],"publication_contexts":[{"context_id":"disorder:Leiomyosarcoma","publication":"PMID:5762758"}],"publication":"PMID:5762758","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/5762758","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Leiomyosarcoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Leiomyosarcoma","name":"Leiomyosarcoma","kind":"Disorder","source_path":"kb/disorders/Leiomyosarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Leiomyosarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Leiomyosarcoma.html#dataset-ega-egas00001002437"}],"context_names":["Leiomyosarcoma"],"disease_names":["Leiomyosarcoma"],"disease_name":"Leiomyosarcoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Leiomyosarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Leiomyosarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Leiomyosarcoma.html#dataset-ega-egas00001002437"]},{"id":"dataset:ega:egas00001002454","accession":"ega:EGAS00001002454","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002454","title":"Natural genetic variation of the cardiac transcriptome in non-diseased donors and patients with dilated cardiomyopathy","alternate_titles":[],"description":"Background: Genetic variation is an important determinant of RNA transcription and splicing, which in turn contributes to variation in human traits including cardiovascular diseases.Results: Here we report the first in-depth survey of heart transcriptome variation using RNA-sequencing in 149 (97)* patients with dilated cardiomyopathy and 113 (108)* non-diseased controls. We reveal extensive differences of gene expression and splicing between dilated cardiomyopathy patients and controls, affecting known as well as novel dilated cardiomyopathy genes. Moreover, we show a widespread effect of genetic variation on the regulation of transcription, isoform usage and allele specific expression.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:28903782"],"publication_contexts":[{"context_id":"disorder:Dilated_Cardiomyopathy","publication":"PMID:28903782"}],"publication":"PMID:28903782","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/28903782","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Dilated Cardiomyopathy\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Dilated_Cardiomyopathy","name":"Dilated Cardiomyopathy","kind":"Disorder","source_path":"kb/disorders/Dilated_Cardiomyopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dilated_Cardiomyopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy.html#dataset-ega-egas00001002454"}],"context_names":["Dilated Cardiomyopathy"],"disease_names":["Dilated Cardiomyopathy"],"disease_name":"Dilated Cardiomyopathy","same_context_model_ids":["model:kb/disorders/Dilated_Cardiomyopathy.yaml:Patient-specific TNNT2 R173W iPSC-derived cardiomyocytes (Clinical Trials in a Dish)"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Dilated_Cardiomyopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dilated_Cardiomyopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy.html#dataset-ega-egas00001002454"]},{"id":"dataset:ega:egas00001002485","accession":"ega:EGAS00001002485","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002485","title":"Coding and small non-coding transcriptional landscape of tuberous sclerosis complex cortical tubers: implications for pathophysiology and treatment","alternate_titles":[],"description":"Tuberous Sclerosis Complex (TSC) is a rare genetic disorder that results from a mutation in the TSC1 or TSC2 genes leading to constitutive activation of the mechanistic target of rapamycin complex 1 (mTORC1). TSC is associated with autism, intellectual disability and severe epilepsy. Cortical tubers are believed to represent the neuropathological substrates of these disabling manifestations in TSC. In the presented study we used high-throughput RNA sequencing in combination with systems-based computational approaches to investigate the complexity of the TSC molecular network.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Tuberous Sclerosis Complex\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Tuberous_Sclerosis_Complex","name":"Tuberous Sclerosis Complex","kind":"Disorder","source_path":"kb/disorders/Tuberous_Sclerosis_Complex.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Tuberous_Sclerosis_Complex.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Tuberous_Sclerosis_Complex.html#dataset-ega-egas00001002485"}],"context_names":["Tuberous Sclerosis Complex"],"disease_names":["Tuberous Sclerosis Complex"],"disease_name":"Tuberous Sclerosis Complex","same_context_model_ids":["model:kb/disorders/Tuberous_Sclerosis_Complex.yaml:CRISPR-engineered TSC2 conditional-biallelic human cortical spheroids","model:kb/disorders/Tuberous_Sclerosis_Complex.yaml:TSC human cerebral organoids with caudal late interneuron progenitor (CLIP) over-proliferation","model:kb/disorders/Tuberous_Sclerosis_Complex.yaml:TSC patient-derived neurovascular unit (iPSC blood-brain-barrier chip)"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Tuberous_Sclerosis_Complex.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Tuberous_Sclerosis_Complex.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Tuberous_Sclerosis_Complex.html#dataset-ega-egas00001002485"]},{"id":"dataset:ega:egas00001002511","accession":"ega:EGAS00001002511","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002511","title":"Genomic and epigenomic characterization of juvenile myelomonocytic leukemia (JMML)","alternate_titles":[],"description":"Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative disorder of early childhood. While some cases show spontaneous remission, allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative treatment option for the majority of patients, however, the 5-year event-free survival reaches only about 50%. Hyperactive RAS signaling is assumed to be the main driving event in JMML. It is caused by genetic alterations in CBL, KRAS, NF1, NRAS, or PTPN11 in about 90% of patients. So far, there is no clear understanding of how RAS pathway mutations relate to the heterogeneous disease biology and variable clinical outcome seen in JMML patients.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Juvenile Myelomonocytic Leukemia\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Juvenile_Myelomonocytic_Leukemia","name":"Juvenile Myelomonocytic Leukemia","kind":"Disorder","source_path":"kb/disorders/Juvenile_Myelomonocytic_Leukemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Juvenile_Myelomonocytic_Leukemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Juvenile_Myelomonocytic_Leukemia.html#dataset-ega-egas00001002511"}],"context_names":["Juvenile Myelomonocytic Leukemia"],"disease_names":["Juvenile Myelomonocytic Leukemia"],"disease_name":"Juvenile Myelomonocytic Leukemia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Juvenile_Myelomonocytic_Leukemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Juvenile_Myelomonocytic_Leukemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Juvenile_Myelomonocytic_Leukemia.html#dataset-ega-egas00001002511"]},{"id":"dataset:ega:egas00001002539","accession":"ega:EGAS00001002539","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002539","title":"Multi-region sequencing of metastatic colorectal cancer","alternate_titles":[],"description":"In order to reconstruct the evolutionary history of metastatic colorectal cancer, we performed whole-exome sequencing of 10 metastatic colorectal cancer patients for whom the primary tumor and matched distant metastases to the brain (n=10), liver (n=1), lung (n=1), as well as lymph node metastases (n=4) were available. For 6 of the 10 patients, multiple regions (n=2-5) of the primary tumor and distant metastases were sequenced.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Metastatic Colorectal Cancer\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Colon_Adenocarcinoma","name":"Colon Adenocarcinoma","kind":"Disorder","source_path":"kb/disorders/Colon_Adenocarcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Colon_Adenocarcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Colon_Adenocarcinoma.html#dataset-ega-egas00001002539"}],"context_names":["Colon Adenocarcinoma"],"disease_names":["Colon Adenocarcinoma"],"disease_name":"Colon Adenocarcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Colon_Adenocarcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Colon_Adenocarcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Colon_Adenocarcinoma.html#dataset-ega-egas00001002539"]},{"id":"dataset:ega:egas00001002547","accession":"ega:EGAS00001002547","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002547","title":"Clonal evolution study of Intrahepatic cholangiocarcinoma in Zhongshan Hospital","alternate_titles":[],"description":"Clonal evolution study of Intrahepatic cholangiocarcinoma","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Cholangiocarcinoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Cholangiocarcinoma","name":"Cholangiocarcinoma","kind":"Disorder","source_path":"kb/disorders/Cholangiocarcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cholangiocarcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cholangiocarcinoma.html#dataset-ega-egas00001002547"}],"context_names":["Cholangiocarcinoma"],"disease_names":["Cholangiocarcinoma"],"disease_name":"Cholangiocarcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cholangiocarcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cholangiocarcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cholangiocarcinoma.html#dataset-ega-egas00001002547"]},{"id":"dataset:ega:egas00001002550","accession":"ega:EGAS00001002550","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002550","title":"High frequency of RUNX1 mutation in myelodysplastic syndrome patients with whole-arm translocation of der(1;7)(q10;p10).","alternate_titles":[],"description":"The der(1;7)(q10;p10) is a recurrent chromosomal abnormality in MDS, resulting in trisomy 1q and monosomy 7q. There is some controversy over the prognosis of the der(1;7)(q10;p10). The genetic basis of MDS patients with der(1;7)(q10;p10) remains poorly defined. In this study, we have documented the disease features and the mutational landscape of a series of patients with der(1;7)(q10;p10). We observed that MDS patients with der(1;7)(q10;p10) present male predominance and have a better outcome than the -7/del(7q) group. Our findings revealed that the mutatome of patients with der(1;7)(q10;p10) is different from that of MDS with -7/del(7q).","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Myelodysplastic Syndrome\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Myelodysplastic_Syndrome","name":"Myelodysplastic Syndrome","kind":"Disorder","source_path":"kb/disorders/Myelodysplastic_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myelodysplastic_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Myelodysplastic_Syndrome.html#dataset-ega-egas00001002550"}],"context_names":["Myelodysplastic Syndrome"],"disease_names":["Myelodysplastic Syndrome"],"disease_name":"Myelodysplastic Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Myelodysplastic_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myelodysplastic_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Myelodysplastic_Syndrome.html#dataset-ega-egas00001002550"]},{"id":"dataset:ega:egas00001002612","accession":"ega:EGAS00001002612","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002612","title":"The genomic landscape of cutaneous squamous cell carcinoma from immunosuppressed and immunocompetent patients reveals common drivers and a novel mutational signature associated with chronic azathioprine exposure","alternate_titles":[],"description":"Cutaneous squamous cell carcinoma (cSCC) has a high tumour mutational burden (50 mutations per megabase DNA pair). Combining whole exome analyses from 40 primary cSCC tumours, comprising 20 well differentiated and 20 moderately/poorly differentiated tumours, with accompanying clinical data from a longitudinal study of immunosuppressed and immunocompetent patients, coupled with integration of independent gene expression studies has allowed the identification of commonly mutated genes and altered pathways and processes.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Cutaneous Squamous Cell Carcinoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Cutaneous_Squamous_Cell_Carcinoma","name":"Cutaneous Squamous Cell Carcinoma","kind":"Disorder","source_path":"kb/disorders/Cutaneous_Squamous_Cell_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cutaneous_Squamous_Cell_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cutaneous_Squamous_Cell_Carcinoma.html#dataset-ega-egas00001002612"}],"context_names":["Cutaneous Squamous Cell Carcinoma"],"disease_names":["Cutaneous Squamous Cell Carcinoma"],"disease_name":"Cutaneous Squamous Cell Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cutaneous_Squamous_Cell_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cutaneous_Squamous_Cell_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cutaneous_Squamous_Cell_Carcinoma.html#dataset-ega-egas00001002612"]},{"id":"dataset:ega:egas00001002632","accession":"ega:EGAS00001002632","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002632","title":"Loss-of-activity-mutation in the cardiac chloride-bicarbonate exchanger AE3 causes short QT syndrome","alternate_titles":[],"description":"Patients with short QT syndrome (SQTS) may present with syncope, ventricular fibrillation or sudden cardiac death. Six SQTS susceptibility genes, encoding cation channels, explain less than 25% of SQTS cases. Here we identify a missense mutation in the anion exchanger (AE3)-encoding SLC4A3 gene in two unrelated families with SQTS. The mutation causes reduced surface expression of AE3 and reduced membrane bicarbonate transport. Slc4a3 knockdown in zebrafish causes increased cardiac pHi, short QTc, and reduced systolic duration, which is rescued by wildtype but not mutated SLC4A3.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Short QT Syndrome\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Short_QT_Syndrome","name":"Short QT Syndrome","kind":"Disorder","source_path":"kb/disorders/Short_QT_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Short_QT_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Short_QT_Syndrome.html#dataset-ega-egas00001002632"}],"context_names":["Short QT Syndrome"],"disease_names":["Short QT Syndrome"],"disease_name":"Short QT Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Short_QT_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Short_QT_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Short_QT_Syndrome.html#dataset-ega-egas00001002632"]},{"id":"dataset:ega:egas00001002637","accession":"ega:EGAS00001002637","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002637","title":"HDAC inhibitors in synovial sarcoma cells","alternate_titles":[],"description":"Histone deacetylase (HDAC) inhibition has been shown in previous studies to disrupt the synovial sarcoma oncoprotein complex, resulting in apoptosis. To understand the molecular effects of HDAC inhibition, RNA-Seq transcriptome analysis was undertaken in six human synovial sarcoma cell lines. HDAC inhibition induced pathways of cell cycle arrest, neuronal differentiation and response to oxygen-containing species, effects also observed in other cancers treated with this class of drugs. More specific to synovial sarcoma, polycomb-group targets were reactivated including tumor suppressor CDKN2A, and pro-apoptotic transcriptional patterns were induced.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Synovial Sarcoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Synovial_Sarcoma","name":"Synovial Sarcoma","kind":"Disorder","source_path":"kb/disorders/Synovial_Sarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Synovial_Sarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Synovial_Sarcoma.html#dataset-ega-egas00001002637"}],"context_names":["Synovial Sarcoma"],"disease_names":["Synovial Sarcoma"],"disease_name":"Synovial Sarcoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Synovial_Sarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Synovial_Sarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Synovial_Sarcoma.html#dataset-ega-egas00001002637"]},{"id":"dataset:ega:egas00001002670","accession":"ega:EGAS00001002670","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002670","title":"We performed whole-exome sequencing of 20 samples (10 actinic keratosis and 10 cutaneous squamous cell carcinoma) to investigate a potential relationship between DNA methylation-based subtypes and genetic mutation patterns (Rodriguez-Paredes et al., Nat Commun 2017)","alternate_titles":[],"description":"Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer type and arises from keratinocytes. Most cSCC progress from a UV-induced precancerous lesion termed actinic keratosis (AK). Despite various efforts to characterize these lesions molecularly, the etiology of AK and its progression to cSCC remain only partially understood. Here we have used Infinium MethylationEPIC BeadChips to interrogate the DNA methylation status of about 850.000 CpGs in epidermal preparations from healthy skin, AK and cSCC. Importantly, we found that the premalignant AK samples displayed classical features of cancer methylomes and were highly similar to cSCC methylomes.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Cutaneous Squamous Cell Carcinoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Cutaneous_Squamous_Cell_Carcinoma","name":"Cutaneous Squamous Cell Carcinoma","kind":"Disorder","source_path":"kb/disorders/Cutaneous_Squamous_Cell_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cutaneous_Squamous_Cell_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cutaneous_Squamous_Cell_Carcinoma.html#dataset-ega-egas00001002670"}],"context_names":["Cutaneous Squamous Cell Carcinoma"],"disease_names":["Cutaneous Squamous Cell Carcinoma"],"disease_name":"Cutaneous Squamous Cell Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cutaneous_Squamous_Cell_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cutaneous_Squamous_Cell_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cutaneous_Squamous_Cell_Carcinoma.html#dataset-ega-egas00001002670"]},{"id":"dataset:ega:egas00001002698","accession":"ega:EGAS00001002698","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002698","title":"Gut microbiome modulates response to anti PD1 immunotherapy in metastatic melanoma patients","alternate_titles":[],"description":"There is a growing appreciation of the role of the microbiome in cancer, and evidence in pre-clinical models that the gut microbiome may modulate responses to immune checkpoint blockade though this has not been well-characterized in patients. We analyzed the oral (n=86)and gut (n=43) 16S microbiome in melanoma patients on PD-1 blockade. Significant differences were noted in the diversity and composition of the gut microbiome between responders and non-responders in patients with a fecal microbiome sample, with significantly higher alpha diversity and relative abundance of Ruminococcaceae bacteria) in R.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:29097493"],"publication_contexts":[{"context_id":"disorder:Cutaneous_Melanoma","publication":"PMID:29097493"}],"publication":"PMID:29097493","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/29097493","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Metastatic Melanoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Cutaneous_Melanoma","name":"Cutaneous Melanoma","kind":"Disorder","source_path":"kb/disorders/Cutaneous_Melanoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cutaneous_Melanoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cutaneous_Melanoma.html#dataset-ega-egas00001002698"}],"context_names":["Cutaneous Melanoma"],"disease_names":["Cutaneous Melanoma"],"disease_name":"Cutaneous Melanoma","same_context_model_ids":["model:kb/disorders/Cutaneous_Melanoma.yaml:Xmrk-activated melanocytes in three-dimensional dermal collagen"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Cutaneous_Melanoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cutaneous_Melanoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cutaneous_Melanoma.html#dataset-ega-egas00001002698"]},{"id":"dataset:ega:egas00001002700","accession":"ega:EGAS00001002700","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002700","title":"Genome-wide DNA Methylation is Predictive of Outcome in Juvenile Myelomonocytic Leukemia","alternate_titles":[],"description":"Juvenile myelomonocytic leukemia (JMML) is a myeloproliferative disorder of childhood caused by mutations in the Ras pathway. Outcomes in this disease vary dramatically from spontaneous resolution with little or no treatment to rapid relapse after hematopoietic stem cell transplantation. Given the high morbidity and late effects of transplant, it is critical to identify patients at diagnosis who can be observed rather than transplanted. We hypothesized that assessing DNA methylation status would help predict disease outcome. Genome-wide DNA methylation profiling using the Illumina 450k platform in a discovery cohort of 39 patients was performed.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:29259179"],"publication_contexts":[{"context_id":"disorder:Juvenile_Myelomonocytic_Leukemia","publication":"PMID:29259179"}],"publication":"PMID:29259179","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/29259179","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Juvenile Myelomonocytic Leukemia\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Juvenile_Myelomonocytic_Leukemia","name":"Juvenile Myelomonocytic Leukemia","kind":"Disorder","source_path":"kb/disorders/Juvenile_Myelomonocytic_Leukemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Juvenile_Myelomonocytic_Leukemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Juvenile_Myelomonocytic_Leukemia.html#dataset-ega-egas00001002700"}],"context_names":["Juvenile Myelomonocytic Leukemia"],"disease_names":["Juvenile Myelomonocytic Leukemia"],"disease_name":"Juvenile Myelomonocytic Leukemia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Juvenile_Myelomonocytic_Leukemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Juvenile_Myelomonocytic_Leukemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Juvenile_Myelomonocytic_Leukemia.html#dataset-ega-egas00001002700"]},{"id":"dataset:ega:egas00001002707","accession":"ega:EGAS00001002707","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002707","title":"Sequencing-based counting and size profiling of plasma Epstein-Barr virus DNA enhance population screening of nasopharyngeal carcinoma.","alternate_titles":[],"description":"Circulating tumor-derived DNA testing for cancer screening has recently been demonstrated in a prospective study on identification of nasopharyngeal carcinoma (NPC) among 20,174 asymptomatic individuals. Plasma EBV DNA, a marker for NPC, was detected using real-time PCR. While plasma EBV DNA was persistently detectable in 97.1% of the NPCs identified, ∼5% of the general population had transiently detectable plasma EBV DNA. We hypothesized that EBV DNA in plasma of subjects with or without NPC may have different molecular characteristics.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:29760067"],"publication_contexts":[{"context_id":"disorder:Nasopharyngeal_Carcinoma","publication":"PMID:29760067"}],"publication":"PMID:29760067","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/29760067","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Nasopharyngeal Carcinoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Nasopharyngeal_Carcinoma","name":"Nasopharyngeal Carcinoma","kind":"Disorder","source_path":"kb/disorders/Nasopharyngeal_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Nasopharyngeal_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Nasopharyngeal_Carcinoma.html#dataset-ega-egas00001002707"}],"context_names":["Nasopharyngeal Carcinoma"],"disease_names":["Nasopharyngeal Carcinoma"],"disease_name":"Nasopharyngeal Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Nasopharyngeal_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Nasopharyngeal_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Nasopharyngeal_Carcinoma.html#dataset-ega-egas00001002707"]},{"id":"dataset:ega:egas00001002720","accession":"ega:EGAS00001002720","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002720","title":"Defective Homologous Recombination DNA Repair as Therapeutic Target in Advanced-Stage Chordoma (HIPO_021)","alternate_titles":[],"description":"HIPO project: HIPO_021 Importance: Chordomas are rare tumors of the axial skeleton and skull base with few therapeutic options and no clinically validated molecular drug targets.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Chordoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Chordoma","name":"Chordoma","kind":"Disorder","source_path":"kb/disorders/Chordoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chordoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chordoma.html#dataset-ega-egas00001002720"}],"context_names":["Chordoma"],"disease_names":["Chordoma"],"disease_name":"Chordoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chordoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chordoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chordoma.html#dataset-ega-egas00001002720"]},{"id":"dataset:ega:egas00001002730","accession":"ega:EGAS00001002730","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002730","title":"Brain transcriptome of hereditary cerebral haemorrhage with amyloidosis–Dutch type (HCHWA-D)","alternate_titles":[],"description":"HCHWA-D is an early onset hereditary form of Cerebral Amyloid Angiopathy (CAA) caused by a point mutation resulting in an amino acid change (NP_000475.1:p.Glu693Gln) in the Amyloid Precursor Protein (APP). Post-mortem brain tissue (9 patients and 9 age-related controls; frontal and occipital cortex) was used for next generation sequencing of RNA (RNA-Seq with ribosomal RNA depletion).","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Amyloidosis\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Amyloidosis","name":"Amyloidosis","kind":"Disorder","source_path":"kb/disorders/Amyloidosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Amyloidosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Amyloidosis.html#dataset-ega-egas00001002730"}],"context_names":["Amyloidosis"],"disease_names":["Amyloidosis"],"disease_name":"Amyloidosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Amyloidosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Amyloidosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Amyloidosis.html#dataset-ega-egas00001002730"]},{"id":"dataset:ega:egas00001002751","accession":"ega:EGAS00001002751","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002751","title":"Antisense long non-coding RNAs are deregulated in skin tissue of patients with systemic sclerosis","alternate_titles":[],"description":"Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of skin and multiple organs of which the pathogenesis is poorly understood. Here we studied differentially expressed coding and non-coding genes in relation to SSc pathogenesis with a specific focus on antisense non-coding RNAs. Skin biopsy-derived RNAs from fourteen early SSc patients and six healthy individuals were sequenced with ion-torrent and analysed using DEseq2. Overall, 4901 genes with a fold change >1.5 and a false discovery rate < 5% were detected in patients versus controls. Upregulated genes clustered in immunological, cell adhesion and keratin-related processes.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:29179949"],"publication_contexts":[{"context_id":"disorder:Systemic_Sclerosis","publication":"PMID:29179949"}],"publication":"PMID:29179949","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/29179949","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Systemic Sclerosis\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Systemic_Sclerosis","name":"Systemic Sclerosis","kind":"Disorder","source_path":"kb/disorders/Systemic_Sclerosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Systemic_Sclerosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Systemic_Sclerosis.html#dataset-ega-egas00001002751"}],"context_names":["Systemic Sclerosis"],"disease_names":["Systemic Sclerosis"],"disease_name":"Systemic Sclerosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Systemic_Sclerosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Systemic_Sclerosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Systemic_Sclerosis.html#dataset-ega-egas00001002751"]},{"id":"dataset:ega:egas00001002756","accession":"ega:EGAS00001002756","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002756","title":"GWAS in a dengue Thai cohort","alternate_titles":[],"description":"Around 700,000 SNPs were genotyped in 290 controls, 252 dengue fever patients and 159 dengue shock syndrome patients from Thailand.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Dengue\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Dengue","name":"Dengue","kind":"Disorder","source_path":"kb/disorders/Dengue.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dengue.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Dengue.html#dataset-ega-egas00001002756"}],"context_names":["Dengue"],"disease_names":["Dengue"],"disease_name":"Dengue","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Dengue.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dengue.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Dengue.html#dataset-ega-egas00001002756"]},{"id":"dataset:ega:egas00001002761","accession":"ega:EGAS00001002761","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002761","title":"Comprehensive genetic analysis of uveal melanoma heterogeneity during metastatic progression","alternate_titles":[],"description":"Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Despite improvement of diagnosis and treatment of the primary tumor, there is no effective treatment of metastatic disease and approximately half of patients will die within one year or less following metastases detection. Tumor heterogeneity has been proposed as a key factor of drug resistance. However, it has been scarcely studied in UM. The present project aims searching for specific drivers of the metastatic progression, describing the genomic and transcriptomic landscape of metastatic UM, exploring tumor heterogeneity and investigating its role in drug resistance.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:29760383"],"publication_contexts":[{"context_id":"disorder:Uveal_Melanoma","publication":"PMID:29760383"}],"publication":"PMID:29760383","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/29760383","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Uveal Melanoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Uveal_Melanoma","name":"Uveal Melanoma","kind":"Disorder","source_path":"kb/disorders/Uveal_Melanoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Uveal_Melanoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Uveal_Melanoma.html#dataset-ega-egas00001002761"}],"context_names":["Uveal Melanoma"],"disease_names":["Uveal Melanoma"],"disease_name":"Uveal Melanoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Uveal_Melanoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Uveal_Melanoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Uveal_Melanoma.html#dataset-ega-egas00001002761"]},{"id":"dataset:ega:egas00001002772","accession":"ega:EGAS00001002772","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002772","title":"An integrated molecular study of 20 hepatoblastoma pairs using whole genome sequencing and RNA sequencing","alternate_titles":[],"description":"Hepatoblastoma is an uncommon malignant liver cancer occurring in infants and children. The mutant background of hepatoblastoma has not been fully demonstrated. The aim of this study is to genomically depict the mutational landscape of hepatoblastoma through an integrative analysis of whole genome sequencing and RNA sequencing of 20 hepatoblastomas from Chinese individuals.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Hepatoblastoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Hepatoblastoma","name":"Hepatoblastoma","kind":"Disorder","source_path":"kb/disorders/Hepatoblastoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatoblastoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hepatoblastoma.html#dataset-ega-egas00001002772"}],"context_names":["Hepatoblastoma"],"disease_names":["Hepatoblastoma"],"disease_name":"Hepatoblastoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hepatoblastoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatoblastoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hepatoblastoma.html#dataset-ega-egas00001002772"]},{"id":"dataset:ega:egas00001002780","accession":"ega:EGAS00001002780","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002780","title":"Investigating the genetic cause of diabetes and hyperinsulinism","alternate_titles":[],"description":"This study includes samples sequenced for the investigation of neonatal diabetes, MODY, hyperinsulinism, and related diseases.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Hyperinsulinism\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Congenital_Isolated_Hyperinsulinism","name":"Congenital Isolated Hyperinsulinism","kind":"Disorder","source_path":"kb/disorders/Congenital_Isolated_Hyperinsulinism.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Congenital_Isolated_Hyperinsulinism.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Congenital_Isolated_Hyperinsulinism.html#dataset-ega-egas00001002780"}],"context_names":["Congenital Isolated Hyperinsulinism"],"disease_names":["Congenital Isolated Hyperinsulinism"],"disease_name":"Congenital Isolated Hyperinsulinism","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Congenital_Isolated_Hyperinsulinism.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Congenital_Isolated_Hyperinsulinism.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Congenital_Isolated_Hyperinsulinism.html#dataset-ega-egas00001002780"]},{"id":"dataset:ega:egas00001002797","accession":"ega:EGAS00001002797","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002797","title":"DNA hypermethylation and differential gene expression associated with Klinefelter syndrome","alternate_titles":[],"description":"The molecular basis for the phenotypic traits and morbidity in Klinefelter syndrome (KS) are not clarified. As DNA methylation affect gene expression and thereby play a role in disease susceptibility, we performed genome-wide DNA methylation profiling of leucocytes from peripheral blood samples from 67 KS patients, 67 male controls and 33 female controls, in addition to genome-wide RNA-sequencing profiling in a subset of 9 KS patients, 9 control males and 13 female controls. Characterization of the methylome as well as the transcriptome of both coding and non-coding genes identified a unique epigenetic and genetic landscape of both autosomal chromosomes as well as the X chromosome in KS.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Klinefelter Syndrome\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Klinefelter_Syndrome","name":"Klinefelter Syndrome","kind":"Disorder","source_path":"kb/disorders/Klinefelter_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Klinefelter_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Klinefelter_Syndrome.html#dataset-ega-egas00001002797"}],"context_names":["Klinefelter Syndrome"],"disease_names":["Klinefelter Syndrome"],"disease_name":"Klinefelter Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Klinefelter_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Klinefelter_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Klinefelter_Syndrome.html#dataset-ega-egas00001002797"]},{"id":"dataset:ega:egas00001002807","accession":"ega:EGAS00001002807","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002807","title":"Genomic profiling of matched well differentiated and de-differentiated liposarcoma.","alternate_titles":[],"description":"Well-differentiated (WD) and de-differentiated (DD) liposarcoma, subtypes of adipocytic sarcomas, are pathologically and clinically dissimilar, but are poorly distinguishable at the molecular level. These tumors harbor neochromosomes formed from amplifications and rearrangements of chr12q. Nineteen selected patients with matched WD and DD tumors underwent extensive exomic and transcriptomic profiling to distinguish genomic features between the two subtypes. Shared point mutations suggest a common tumor origin and de-differentiated tumors have higher burdens of deletions.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Liposarcoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Liposarcoma","name":"Liposarcoma","kind":"Disorder","source_path":"kb/disorders/Liposarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Liposarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Liposarcoma.html#dataset-ega-egas00001002807"}],"context_names":["Liposarcoma"],"disease_names":["Liposarcoma"],"disease_name":"Liposarcoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Liposarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Liposarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Liposarcoma.html#dataset-ega-egas00001002807"]},{"id":"dataset:ega:egas00001002811","accession":"ega:EGAS00001002811","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002811","title":"Whole-Exome Sequencing of Salivary Gland Mucoepidermoid Carcinoma","alternate_titles":[],"description":"Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy. To explore the genetic origins of MEC, we performed systematic genomic analyses of these tumors.Experimental DesignWhole-exome sequencing and gene copy number analyses were performed for 18 primary cancers with matched normal tissue. Fluorescence in situ hybridization (FISH) was used to determine the presence or absence of the MECT1-MAML2 translocation in 17 tumors.ResultsTP53 was the most commonly mutated gene in MEC (28%), and mutations were found only in intermediate- and high-grade tumors. Tumors with TP53 mutations had more mutations overall than tumors without TP53 mutations (p=0.006).","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:5182193"],"publication_contexts":[{"context_id":"disorder:Mucoepidermoid_Carcinoma","publication":"PMID:5182193"}],"publication":"PMID:5182193","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/5182193","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Mucoepidermoid Carcinoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Mucoepidermoid_Carcinoma","name":"Mucoepidermoid Carcinoma","kind":"Disorder","source_path":"kb/disorders/Mucoepidermoid_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mucoepidermoid_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Mucoepidermoid_Carcinoma.html#dataset-ega-egas00001002811"}],"context_names":["Mucoepidermoid Carcinoma"],"disease_names":["Mucoepidermoid Carcinoma"],"disease_name":"Mucoepidermoid Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Mucoepidermoid_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mucoepidermoid_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Mucoepidermoid_Carcinoma.html#dataset-ega-egas00001002811"]},{"id":"dataset:ega:egas00001002818","accession":"ega:EGAS00001002818","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002818","title":"Whole-exome ultra-high throughput sequencing in brain samples of suicide victims who had suffered from major depressive disorder and control subjects who had died from other causes","alternate_titles":[],"description":"We carried out whole-exome ultra-high throughput sequencing in brain samples of suicide victims who had suffered from major depressive disorder and control subjects who had died from other causes. This study aimed to reveal the selective accumulation of rare variants in the coding and the UTR sequences within the genes of suicide victims. We also analysed the potential effect of STR and CNV variations, as well as the infection of the brain with neurovirulent viruses in this behavioural disorder. As a result, we have identified several candidate genes, among others three calcium channel genes that may potentially contribute to completed suicide.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Major Depressive Disorder\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Major_Depressive_Disorder","name":"Major Depressive Disorder","kind":"Disorder","source_path":"kb/disorders/Major_Depressive_Disorder.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Major_Depressive_Disorder.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Major_Depressive_Disorder.html#dataset-ega-egas00001002818"}],"context_names":["Major Depressive Disorder"],"disease_names":["Major Depressive Disorder"],"disease_name":"Major Depressive Disorder","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Major_Depressive_Disorder.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Major_Depressive_Disorder.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Major_Depressive_Disorder.html#dataset-ega-egas00001002818"]},{"id":"dataset:ega:egas00001002820","accession":"ega:EGAS00001002820","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002820","title":"Molecular subtypes of malignant peritoneal mesothelioma","alternate_titles":[],"description":"Malignant Peritoneal Mesothelioma (PeM) is a rare but frequently fatal cancer that originates from the peritoneal lining of the abdomen. Standard treatment of PeM is limited to cytoreductive surgery and/or chemotherapy, and no targeted therapies for PeM yet exist. This study performs comprehensive integrative analysis of genome, transcriptome, and proteome of treatment-naive PeM tumors with the aim of identifying mesothelioma-related molecular alterations and potentially identifying novel treatment strategies.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Malignant Peritoneal Mesothelioma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Malignant_Peritoneal_Mesothelioma","name":"Malignant Peritoneal Mesothelioma","kind":"Disorder","source_path":"kb/disorders/Malignant_Peritoneal_Mesothelioma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Malignant_Peritoneal_Mesothelioma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Malignant_Peritoneal_Mesothelioma.html#dataset-ega-egas00001002820"}],"context_names":["Malignant Peritoneal Mesothelioma"],"disease_names":["Malignant Peritoneal Mesothelioma"],"disease_name":"Malignant Peritoneal Mesothelioma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Malignant_Peritoneal_Mesothelioma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Malignant_Peritoneal_Mesothelioma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Malignant_Peritoneal_Mesothelioma.html#dataset-ega-egas00001002820"]},{"id":"dataset:ega:egas00001002860","accession":"ega:EGAS00001002860","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002860","title":"Whole-genome and transcriptome sequencing of tumor-stage mycosis fungoides","alternate_titles":[],"description":"Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma (CTCL), a group of malignancies derived from skin-homing malignant T cells. We subjected tumor biopsies from MF patients to whole-genome sequencing and RNA-sequencing to investigate genomic alterations and deregulated gene expression in the disease.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Mycosis Fungoides\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Mycosis_Fungoides","name":"Mycosis Fungoides","kind":"Disorder","source_path":"kb/disorders/Mycosis_Fungoides.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mycosis_Fungoides.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Mycosis_Fungoides.html#dataset-ega-egas00001002860"}],"context_names":["Mycosis Fungoides"],"disease_names":["Mycosis Fungoides"],"disease_name":"Mycosis Fungoides","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Mycosis_Fungoides.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mycosis_Fungoides.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Mycosis_Fungoides.html#dataset-ega-egas00001002860"]},{"id":"dataset:ega:egas00001002901","accession":"ega:EGAS00001002901","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002901","title":"Hypothalamic transcriptome in Prader-Willi syndrome","alternate_titles":[],"description":"Transcriptional analysis of brain tissue from people with molecularly defined causes of obesity may highlight novel disease mechanisms and therapeutic targets. Prader-Willi syndrome (PWS) is a genetic obesity syndrome characterised by severe hyperphagia. We performed RNA sequencing of the hypothalamus from 4 individuals with PWS and 4 age-matched controls.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Prader-Willi Syndrome\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Prader-Willi_Syndrome","name":"Prader-Willi Syndrome","kind":"Disorder","source_path":"kb/disorders/Prader-Willi_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Prader-Willi_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Prader-Willi_Syndrome.html#dataset-ega-egas00001002901"}],"context_names":["Prader-Willi Syndrome"],"disease_names":["Prader-Willi Syndrome"],"disease_name":"Prader-Willi Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Prader-Willi_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Prader-Willi_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Prader-Willi_Syndrome.html#dataset-ega-egas00001002901"]},{"id":"dataset:ega:egas00001002904","accession":"ega:EGAS00001002904","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002904","title":"DNA Methylation and its Relation to Anti-citrullinated Protein Antibody Positivity and Rheumatoid Arthritis from a General Population-based Sample","alternate_titles":[],"description":"Objective: To compare DNA methylation in subjects positive vs. negative for anti-citrullinated protein antibodies (ACPA), a key serological marker of rheumatoid arthritis (RA) risk.Methods: Using banked serum from a random subset (N=3,600) of a large general population cohort (N=20,000), we identified subjects who were ACPA positive, and compared these to age and sex matched ACPA negative controls. We used a custom-designed methylome panel to conduct targeted bisulphite sequencing based investigation of 5M CpGs located in regulatory or hypomethylated regions of circulating blood cells.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Rheumatoid Arthritis\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Rheumatoid_Arthritis","name":"Rheumatoid Arthritis","kind":"Disorder","source_path":"kb/disorders/Rheumatoid_Arthritis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rheumatoid_Arthritis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Rheumatoid_Arthritis.html#dataset-ega-egas00001002904"}],"context_names":["Rheumatoid Arthritis"],"disease_names":["Rheumatoid Arthritis"],"disease_name":"Rheumatoid Arthritis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Rheumatoid_Arthritis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rheumatoid_Arthritis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Rheumatoid_Arthritis.html#dataset-ega-egas00001002904"]},{"id":"dataset:ega:egas00001002920","accession":"ega:EGAS00001002920","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001002920","title":"SS18-SSX-mediated hijacking of BAF complexes drives synovial sarcoma","alternate_titles":[],"description":"Synovial sarcoma (SS) is defined by a recurrent t(x;18) chromosomal translocation, which produces the hallmark SS18-SSX oncogenic fusion. Incorporation of SS18-SSX into BAF complexes renders BAF complexes aberrant in two distinct manners: the addition of 78aa of SSX onto SS18, and concomitant loss of BAF47 assembly. However, the importance and functional contributions of each of these perturbations on BAF complex targeting and gene expression regulation remain unclear. Here we use an integrative set of genomic approaches in human cancer cell lines and primary tumor samples to define the mechanistic consequences of the SS18-SSX fusion oncoprotein.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Synovial Sarcoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Synovial_Sarcoma","name":"Synovial Sarcoma","kind":"Disorder","source_path":"kb/disorders/Synovial_Sarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Synovial_Sarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Synovial_Sarcoma.html#dataset-ega-egas00001002920"}],"context_names":["Synovial Sarcoma"],"disease_names":["Synovial Sarcoma"],"disease_name":"Synovial Sarcoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Synovial_Sarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Synovial_Sarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Synovial_Sarcoma.html#dataset-ega-egas00001002920"]},{"id":"dataset:ega:egas00001003004","accession":"ega:EGAS00001003004","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001003004","title":"Genentech study of gallbladder cancer","alternate_titles":[],"description":"Genomic characterization of gallbladder cancer using Exome-Seq, RNA-Seq and low pass whole genome sequencing.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Gallbladder Cancer\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Gallbladder_Cancer","name":"Gallbladder Cancer","kind":"Disorder","source_path":"kb/disorders/Gallbladder_Cancer.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Gallbladder_Cancer.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Gallbladder_Cancer.html#dataset-ega-egas00001003004"}],"context_names":["Gallbladder Cancer"],"disease_names":["Gallbladder Cancer"],"disease_name":"Gallbladder Cancer","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Gallbladder_Cancer.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Gallbladder_Cancer.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Gallbladder_Cancer.html#dataset-ega-egas00001003004"]},{"id":"dataset:ega:egas00001003017","accession":"ega:EGAS00001003017","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001003017","title":"Celiac disease-specific intestinal T cells analyzed with HLA-class II tetramers, RNA-seq and mass cytometry have a narrow, autoimmune-associated phenotype","alternate_titles":[],"description":"Celiac disease (CD) is an HLA-DQ2/8-associated autoimmune enteropathy driven by activation of gluten-specific CD4+ T lymphocytes upon gluten consumption. Much less is known about the phenotype and function of these cells or their correlation, if any, to disease-relevant cells in other autoimmune disorders. Here we use mass cytometry and RNA seq to show that gluten-specific blood and gut T cells occupy a small and phenotypically distinct T-cell subset.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Celiac Disease\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Celiac_Disease","name":"Celiac Disease","kind":"Disorder","source_path":"kb/disorders/Celiac_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Celiac_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Celiac_Disease.html#dataset-ega-egas00001003017"}],"context_names":["Celiac Disease"],"disease_names":["Celiac Disease"],"disease_name":"Celiac Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Celiac_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Celiac_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Celiac_Disease.html#dataset-ega-egas00001003017"]},{"id":"dataset:ega:egas00001003045","accession":"ega:EGAS00001003045","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001003045","title":"Lone atrial fibrillation case-control study","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Atrial Fibrillation\"); description-level mentions were not accepted. EGA study_type: Population Genomics. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Atrial_Fibrillation","name":"Atrial Fibrillation","kind":"Disorder","source_path":"kb/disorders/Atrial_Fibrillation.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Atrial_Fibrillation.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Atrial_Fibrillation.html#dataset-ega-egas00001003045"}],"context_names":["Atrial Fibrillation"],"disease_names":["Atrial Fibrillation"],"disease_name":"Atrial Fibrillation","same_context_model_ids":["model:kb/disorders/Atrial_Fibrillation.yaml:Palmitate-treated human iPSC-derived atrial cardiomyocytes"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Atrial_Fibrillation.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Atrial_Fibrillation.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Atrial_Fibrillation.html#dataset-ega-egas00001003045"]},{"id":"dataset:ega:egas00001003053","accession":"ega:EGAS00001003053","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001003053","title":"WES analysis in identifying additive genetic factors that may contribute to the occurrence of moyamoya in neurofibromatosis type 1","alternate_titles":[],"description":"Moyamoya is a progressive cerebral vasculopathy, for which genetic susceptibility factors were mainly identified in Asian populations. When associated with other medical conditions, such as neurofibromatosis type 1 (NF1), this vasculopathy is frequently reported as Moyamoya syndrome (MMS). Intriguingly, most cases of MMS-complicated NF1 have been described in Caucasians, inverting the population ratio for moyamoya vasculopathy observed in Asians, despite NF1 prevalence being constant worldwide. This study aims to investigate whether, among Caucasians, additive genetic factors may contribute to the occurrence of MMS in NF1.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Neurofibromatosis Type 1\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Neurofibromatosis_Type_1","name":"Neurofibromatosis Type 1","kind":"Disorder","source_path":"kb/disorders/Neurofibromatosis_Type_1.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Neurofibromatosis_Type_1.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Neurofibromatosis_Type_1.html#dataset-ega-egas00001003053"}],"context_names":["Neurofibromatosis Type 1"],"disease_names":["Neurofibromatosis Type 1"],"disease_name":"Neurofibromatosis Type 1","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Neurofibromatosis_Type_1.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Neurofibromatosis_Type_1.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Neurofibromatosis_Type_1.html#dataset-ega-egas00001003053"]},{"id":"dataset:ega:egas00001003059","accession":"ega:EGAS00001003059","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001003059","title":"Brugada Syndrome-associated Genetic Loci are associated with J-point Elevation and an Increased Risk of Cardiac Arrest","alternate_titles":[],"description":"Introduction: A previous genome-wide association study found three genetic loci, rs9388451, rs10428132, and rs11708996, toincrease the risk of Brugada Syndrome (BrS). Since the effect of these loci in the general population is unknown, we aimed toinvestigate the effect on electrocardiogram (ECG) parameters and outcomes in the general population.Material and Methods: A cohort of 6,161 individuals (median age 45 [interquartile range (IQR) 40-50] years, 49% males), withavailable digital ECGs, was genotyped and subsequently followed for a median period of 13 [IQR 12.6-13.4] years. Data on outcomeswere collected from Danish administrative healthcare registries.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Brugada syndrome\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Brugada_Syndrome","name":"Brugada syndrome","kind":"Disorder","source_path":"kb/disorders/Brugada_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Brugada_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Brugada_syndrome.html#dataset-ega-egas00001003059"}],"context_names":["Brugada syndrome"],"disease_names":["Brugada syndrome"],"disease_name":"Brugada syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Brugada_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Brugada_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Brugada_syndrome.html#dataset-ega-egas00001003059"]},{"id":"dataset:ega:egas00001003081","accession":"ega:EGAS00001003081","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001003081","title":"Whole-exome ultra-high throughput sequencing in brain samples of suicide victims who had suffered from major depressive disorder and control subjects who had died from other causes.","alternate_titles":[],"description":"We carried out whole-exome ultra-high throughput sequencing in brain samples of suicide victims who had suffered from major depressive disorder and control subjects who had died from other causes. This study aimed to reveal the selective accumulation of rare variants in the coding and the UTR sequences within the genes of suicide victims. We also analysed the potential effect of STR and CNV variations, as well as the infection of the brain with neurovirulent viruses in this behavioural disorder. As a result, we have identified several candidate genes, among others three calcium channel genes that may potentially contribute to completed suicide.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Major Depressive Disorder\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Major_Depressive_Disorder","name":"Major Depressive Disorder","kind":"Disorder","source_path":"kb/disorders/Major_Depressive_Disorder.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Major_Depressive_Disorder.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Major_Depressive_Disorder.html#dataset-ega-egas00001003081"}],"context_names":["Major Depressive Disorder"],"disease_names":["Major Depressive Disorder"],"disease_name":"Major Depressive Disorder","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Major_Depressive_Disorder.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Major_Depressive_Disorder.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Major_Depressive_Disorder.html#dataset-ega-egas00001003081"]},{"id":"dataset:ega:egas00001003085","accession":"ega:EGAS00001003085","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001003085","title":"Exome sequencing in bipolar disorder families","alternate_titles":[],"description":"Bipolar disorder (BD) is a major psychiatric disorder affecting around 1% of the global population. BD is characterized by recurrent manic and depressive episodes, and has an estimated heritability of around 70% Research has identified the first BD susceptibility genes. However, the underlying pathways and regulatory networks remain largely unknown. Since research has shown that the cumulative impact of common alleles with small effect appears to explain only around 25-38% of the phenotypic variance for BD, rare variants of high penetrance may also contribute to BD risk.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Bipolar Disorder\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Bipolar_Disorder","name":"Bipolar Disorder","kind":"Disorder","source_path":"kb/disorders/Bipolar_Disorder.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bipolar_Disorder.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Bipolar_Disorder.html#dataset-ega-egas00001003085"}],"context_names":["Bipolar Disorder"],"disease_names":["Bipolar Disorder"],"disease_name":"Bipolar Disorder","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Bipolar_Disorder.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bipolar_Disorder.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Bipolar_Disorder.html#dataset-ega-egas00001003085"]},{"id":"dataset:ega:egas00001003095","accession":"ega:EGAS00001003095","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001003095","title":"Somatic mutations in endometriosis and normal uterine endometrium","alternate_titles":[],"description":"To characterize the genomic features of endometriosis, we performed whole-exome sequencing for ovarian endometriotic epithelium samples obtained from subjects without concurrent gynecological cancers. Additionally, we analyzed histologically normal uterine endometrial epithelium samples obtained from subjects with benign gynecologic diseases. All the epithelium samples were isolated by laser microdissection from frozen sections.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:30110635"],"publication_contexts":[{"context_id":"disorder:Endometriosis","publication":"PMID:30110635"}],"publication":"PMID:30110635","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/30110635","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Endometriosis\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Endometriosis","name":"Endometriosis","kind":"Disorder","source_path":"kb/disorders/Endometriosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Endometriosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Endometriosis.html#dataset-ega-egas00001003095"}],"context_names":["Endometriosis"],"disease_names":["Endometriosis"],"disease_name":"Endometriosis","same_context_model_ids":["model:kb/disorders/Endometriosis.yaml:Droplet-based microfluidic protease-activity profiling platform (PrAMA; MIT Griffith/Han)"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Endometriosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Endometriosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Endometriosis.html#dataset-ega-egas00001003095"]},{"id":"dataset:ega:egas00001003123","accession":"ega:EGAS00001003123","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001003123","title":"Heritable pulmonary arterial hypertension in a large Iberian family","alternate_titles":[],"description":"Data from a study of a large Iberian family (n=65 subjects, 5 generations) affected by pulmonary arterial hypertension (PAH) and segregating with the BMPR2 missense mutation p.Arg491Gln (rs137852749, c.1472G>A). PAH is a rare disease characterized by an abnormal rise in mean pulmonary arterial pressure (> or equal to 25 mmHg at rest), which, in turn, leads to a progressive increase in pulmonary vascular resistance and ultimately to death, due to right ventricular failure. Heritable PAH has an overall prevalence below 1 case per million adults and is defined by either the presence of a known genetic defect linked to the disease or a positive family history.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:30894412"],"publication_contexts":[{"context_id":"disorder:Heritable_Pulmonary_Arterial_Hypertension","publication":"PMID:30894412"}],"publication":"PMID:30894412","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/30894412","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Heritable Pulmonary Arterial Hypertension\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Heritable_Pulmonary_Arterial_Hypertension","name":"Heritable Pulmonary Arterial Hypertension","kind":"Disorder","source_path":"kb/disorders/Heritable_Pulmonary_Arterial_Hypertension.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Heritable_Pulmonary_Arterial_Hypertension.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Heritable_Pulmonary_Arterial_Hypertension.html#dataset-ega-egas00001003123"}],"context_names":["Heritable Pulmonary Arterial Hypertension"],"disease_names":["Heritable Pulmonary Arterial Hypertension"],"disease_name":"Heritable Pulmonary Arterial Hypertension","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Heritable_Pulmonary_Arterial_Hypertension.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Heritable_Pulmonary_Arterial_Hypertension.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Heritable_Pulmonary_Arterial_Hypertension.html#dataset-ega-egas00001003123"]},{"id":"dataset:ega:egas00001003155","accession":"ega:EGAS00001003155","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001003155","title":"High Altitude Pulmonary Hypertension","alternate_titles":[],"description":"The Central Asian Kyrgyz highland population provides a unique opportunity to address genetic diversity and understand the genetic mechanisms underlying hypoxia-induced high altitude pulmonary hypertension (HAPH). While a significant fraction of the population is unaffected, there are susceptible individuals who display HAPH in the absence of any lung, cardiac or hematologic disease. We report herein the analysis of the whole genome sequencing of healthy individuals compared with HAPH patients and other controls.","alternate_descriptions":[],"data_types":["WGS"],"data_type_labels":["Whole genome sequencing"],"data_type_label":"Whole genome sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Pulmonary hypertension\"); description-level mentions were not accepted. EGA study_type: Whole Genome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Pulmonary_hypertension","name":"Pulmonary_hypertension","kind":"Disorder","source_path":"kb/disorders/Pulmonary_hypertension.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pulmonary_hypertension.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pulmonary_hypertension.html#dataset-ega-egas00001003155"}],"context_names":["Pulmonary_hypertension"],"disease_names":["Pulmonary_hypertension"],"disease_name":"Pulmonary_hypertension","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Pulmonary_hypertension.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pulmonary_hypertension.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Pulmonary_hypertension.html#dataset-ega-egas00001003155"]},{"id":"dataset:ega:egas00001003171","accession":"ega:EGAS00001003171","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001003171","title":"High Altitude Pulmonary Hypertension","alternate_titles":[],"description":"The Central Asian Kyrgyz highland population provides a unique opportunity to address genetic diversity and understand the genetic mechanisms underlying hypoxia-induced high altitude pulmonary hypertension (HAPH). While a significant fraction of the population is unaffected, there are susceptible individuals who display HAPH in the absence of any lung, cardiac or hematologic disease. We report herein the analysis of the whole genome sequencing of healthy individuals compared with HAPH patients and other controls.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Pulmonary hypertension\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Pulmonary_hypertension","name":"Pulmonary_hypertension","kind":"Disorder","source_path":"kb/disorders/Pulmonary_hypertension.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pulmonary_hypertension.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pulmonary_hypertension.html#dataset-ega-egas00001003171"}],"context_names":["Pulmonary_hypertension"],"disease_names":["Pulmonary_hypertension"],"disease_name":"Pulmonary_hypertension","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Pulmonary_hypertension.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pulmonary_hypertension.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Pulmonary_hypertension.html#dataset-ega-egas00001003171"]},{"id":"dataset:ega:egas00001003196","accession":"ega:EGAS00001003196","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001003196","title":"Exome-sequencing of paired docetaxel sensitive and resistant triple-negative breast cancer","alternate_titles":[],"description":"Taxane-based regimens constitute the most common therapeutic option in patients with triple-negative breast cancer (TNBC). Resistance to treatment often arises although the molecular mechanisms responsible for this process are unknown. To unravel chemoresistance mechanisms, exome sequencing was performed on matched docetaxel sensitive and resistant TNBC patient-derived xenografts (PDX).","alternate_descriptions":[],"data_types":["WES"],"data_type_labels":["Whole exome sequencing"],"data_type_label":"Whole exome sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Triple-Negative Breast Cancer\"); description-level mentions were not accepted. EGA study_type: Exome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Triple_Negative_Breast_Cancer","name":"Triple-Negative Breast Cancer","kind":"Disorder","source_path":"kb/disorders/Triple_Negative_Breast_Cancer.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Triple_Negative_Breast_Cancer.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Triple-Negative_Breast_Cancer.html#dataset-ega-egas00001003196"}],"context_names":["Triple-Negative Breast Cancer"],"disease_names":["Triple-Negative Breast Cancer"],"disease_name":"Triple-Negative Breast Cancer","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Triple_Negative_Breast_Cancer.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Triple_Negative_Breast_Cancer.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Triple-Negative_Breast_Cancer.html#dataset-ega-egas00001003196"]},{"id":"dataset:ega:egas00001003199","accession":"ega:EGAS00001003199","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001003199","title":"Genome-wide association study of cervical cancer in East Asian populations","alternate_titles":[],"description":"The development of cervical cancer is initiated by human papillomavirus (HPV) infection, and involves both viral and host genetic factors. Genome-wide association studies (GWAS) of cervical cancer have identified associations in the HLA locus and two loci outside HLA, but the principal genes that control infection and pathogenesis have not been identified. In the present study, we performed GWAS of cervical cancer in East Asian populations, involving 2609 cases and 4712 controls in the discovery stage, 1461 cases and 3295 controls in the follow-up stage.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Cervical Cancer\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Cervical_Cancer","name":"Cervical Cancer","kind":"Disorder","source_path":"kb/disorders/Cervical_Cancer.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cervical_Cancer.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cervical_Cancer.html#dataset-ega-egas00001003199"}],"context_names":["Cervical Cancer"],"disease_names":["Cervical Cancer"],"disease_name":"Cervical Cancer","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cervical_Cancer.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cervical_Cancer.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cervical_Cancer.html#dataset-ega-egas00001003199"]},{"id":"dataset:ega:egas00001003207","accession":"ega:EGAS00001003207","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001003207","title":"Whole exome sequencing of 76 individuals with familial atrial fibrillation","alternate_titles":[],"description":"We investigated genetic background of familial and early onset atrial fibrillation (AF) with the aim of identify genes involved in atrial fibrillation pathology and are highly predisposing risk factors. We performed whole exome sequencing on 24 families where three or more family members suffered from AF.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Atrial Fibrillation\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.","European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Familial Atrial Fibrillation\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Atrial_Fibrillation","name":"Atrial Fibrillation","kind":"Disorder","source_path":"kb/disorders/Atrial_Fibrillation.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Atrial_Fibrillation.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Atrial_Fibrillation.html#dataset-ega-egas00001003207"},{"id":"disorder:Familial_Atrial_Fibrillation","name":"Familial Atrial Fibrillation","kind":"Disorder","source_path":"kb/disorders/Familial_Atrial_Fibrillation.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Familial_Atrial_Fibrillation.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Familial_Atrial_Fibrillation.html#dataset-ega-egas00001003207"}],"context_names":["Atrial Fibrillation","Familial Atrial Fibrillation"],"disease_names":["Atrial Fibrillation","Familial Atrial Fibrillation"],"disease_name":"Atrial Fibrillation","same_context_model_ids":["model:kb/disorders/Atrial_Fibrillation.yaml:Palmitate-treated human iPSC-derived atrial cardiomyocytes"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Atrial_Fibrillation.yaml","kb/disorders/Familial_Atrial_Fibrillation.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Atrial_Fibrillation.yaml","https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Familial_Atrial_Fibrillation.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Atrial_Fibrillation.html#dataset-ega-egas00001003207","https://dismech.monarchinitiative.org/pages/disorders/Familial_Atrial_Fibrillation.html#dataset-ega-egas00001003207"]},{"id":"dataset:ega:egas00001003208","accession":"ega:EGAS00001003208","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001003208","title":"early onset lone atrial fibrillation case-control study","alternate_titles":[],"description":"Target sequencing W/ TruSight Cardio Sequencing Kit. 395 early onset lone AF cases and 375 controls. Sequencing was performed on Illumina NextSeq and HiSeq 2500 systems.395 early.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Atrial Fibrillation\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Atrial_Fibrillation","name":"Atrial Fibrillation","kind":"Disorder","source_path":"kb/disorders/Atrial_Fibrillation.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Atrial_Fibrillation.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Atrial_Fibrillation.html#dataset-ega-egas00001003208"}],"context_names":["Atrial Fibrillation"],"disease_names":["Atrial Fibrillation"],"disease_name":"Atrial Fibrillation","same_context_model_ids":["model:kb/disorders/Atrial_Fibrillation.yaml:Palmitate-treated human iPSC-derived atrial cardiomyocytes"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Atrial_Fibrillation.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Atrial_Fibrillation.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Atrial_Fibrillation.html#dataset-ega-egas00001003208"]},{"id":"dataset:ega:egas00001003292","accession":"ega:EGAS00001003292","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001003292","title":"Whole Tumor spatial heterogeneity in metastatic melanoma","alternate_titles":[],"description":"Heterogeneous inter-tumoral responses, sustained periods of apparent clinical benefit despite lack of objective response to various therapies, and even spontaneous remission are well known within a subpopulation of advanced melanoma patients. The molecular and cellular dynamics facilitating long-term survival remain poorly defined, particularly in the current era ofexposure to multiple potentially active therapies.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Metastatic Melanoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Cutaneous_Melanoma","name":"Cutaneous Melanoma","kind":"Disorder","source_path":"kb/disorders/Cutaneous_Melanoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cutaneous_Melanoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cutaneous_Melanoma.html#dataset-ega-egas00001003292"}],"context_names":["Cutaneous Melanoma"],"disease_names":["Cutaneous Melanoma"],"disease_name":"Cutaneous Melanoma","same_context_model_ids":["model:kb/disorders/Cutaneous_Melanoma.yaml:Xmrk-activated melanocytes in three-dimensional dermal collagen"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Cutaneous_Melanoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cutaneous_Melanoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cutaneous_Melanoma.html#dataset-ega-egas00001003292"]},{"id":"dataset:ega:egas00001003343","accession":"ega:EGAS00001003343","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001003343","title":"Exome sequencing of a novel cervical cancer cell line","alternate_titles":[],"description":"Human cancer cell lines are largely used in the searching for new antineoplastic agents. However, due to the artifacts of a long-term in culture, cell lines do not always represent the realistic tumor cell behavior. This has motivated the development of models that better mimetics the tumor tissue, among them, the establishment of primary cell cultures. In this work, we establish and characterized a low-passage cervix cancer cell line from a Brazilian patient with squamous cell carcinoma. The phenotype confirms the epithelial and tumor origin, through cytokeratins, EpCAM, and p16 staining.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:30760827"],"publication_contexts":[{"context_id":"disorder:Cervical_Cancer","publication":"PMID:30760827"}],"publication":"PMID:30760827","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/30760827","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Cervical Cancer\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Cervical_Cancer","name":"Cervical Cancer","kind":"Disorder","source_path":"kb/disorders/Cervical_Cancer.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cervical_Cancer.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cervical_Cancer.html#dataset-ega-egas00001003343"}],"context_names":["Cervical Cancer"],"disease_names":["Cervical Cancer"],"disease_name":"Cervical Cancer","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cervical_Cancer.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cervical_Cancer.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cervical_Cancer.html#dataset-ega-egas00001003343"]},{"id":"dataset:ega:egas00001003435","accession":"ega:EGAS00001003435","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001003435","title":"Trio exome sequencing identified null mutations in ITPA as the cause of Martsolf syndrome with a lethal dilated cardiomyopathy presenting in infancy","alternate_titles":[],"description":"Typical Martsolf syndrome is characterized by congenital cataracts, postnatal microcephaly, developmental delay, hypotonia, short stature and biallelic hypomorphic mutations in either RAB3GAP1 or RAB3GAP2. Genetic analysis of 85 unrelated “mutation negative” probands with Martsolf or Martsolf-like syndromes identified two individuals with different homozygous null mutations in ITPA, the gene encoding inosine triphosphate pyrophosphatase (ITPase). Both probands were from multiplex families with a consistent, lethal and highly distinctive disorder; a Martsolf-like syndrome with infantile-onset dilated cardiomyopathy.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Dilated Cardiomyopathy\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Dilated_Cardiomyopathy","name":"Dilated Cardiomyopathy","kind":"Disorder","source_path":"kb/disorders/Dilated_Cardiomyopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dilated_Cardiomyopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy.html#dataset-ega-egas00001003435"}],"context_names":["Dilated Cardiomyopathy"],"disease_names":["Dilated Cardiomyopathy"],"disease_name":"Dilated Cardiomyopathy","same_context_model_ids":["model:kb/disorders/Dilated_Cardiomyopathy.yaml:Patient-specific TNNT2 R173W iPSC-derived cardiomyocytes (Clinical Trials in a Dish)"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Dilated_Cardiomyopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dilated_Cardiomyopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy.html#dataset-ega-egas00001003435"]},{"id":"dataset:ega:egas00001003462","accession":"ega:EGAS00001003462","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001003462","title":"Whole genome sequencing of 25 South African individuals with myasthenia gravis","alternate_titles":[],"description":"This study investigated the genetic basis of an ophthalmoplegic subphenotype of MG (OP-MG) which occurs in a proportion of myasthenics with juvenile symptom onset and African genetic ancestry. This OP-MG subphenotype is characterised by treatment resistant weakness of the extraocular muscles (EOMs) and the pathogenetic mechanism(s) underlying its development is unknown. The aim of this study was to use a hypothesis-generating genome-wide case-control analysis to identify candidate OP-MG susceptibility genes and pathways.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:30881381"],"publication_contexts":[{"context_id":"disorder:Myasthenia_Gravis","publication":"PMID:30881381"}],"publication":"PMID:30881381","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/30881381","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Myasthenia Gravis\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Myasthenia_Gravis","name":"Myasthenia Gravis","kind":"Disorder","source_path":"kb/disorders/Myasthenia_Gravis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myasthenia_Gravis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Myasthenia_Gravis.html#dataset-ega-egas00001003462"}],"context_names":["Myasthenia Gravis"],"disease_names":["Myasthenia Gravis"],"disease_name":"Myasthenia Gravis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Myasthenia_Gravis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myasthenia_Gravis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Myasthenia_Gravis.html#dataset-ega-egas00001003462"]},{"id":"dataset:ega:egas00001003510","accession":"ega:EGAS00001003510","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001003510","title":"Juvenile Idiopathic Arthritis exome sequencing in a consanguineous family","alternate_titles":[],"description":"Identify the causative gene defect in three affected patients with JIA.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Juvenile Idiopathic Arthritis\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Juvenile_Idiopathic_Arthritis","name":"Juvenile Idiopathic Arthritis","kind":"Disorder","source_path":"kb/disorders/Juvenile_Idiopathic_Arthritis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Juvenile_Idiopathic_Arthritis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Juvenile_Idiopathic_Arthritis.html#dataset-ega-egas00001003510"}],"context_names":["Juvenile Idiopathic Arthritis"],"disease_names":["Juvenile Idiopathic Arthritis"],"disease_name":"Juvenile Idiopathic Arthritis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Juvenile_Idiopathic_Arthritis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Juvenile_Idiopathic_Arthritis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Juvenile_Idiopathic_Arthritis.html#dataset-ega-egas00001003510"]},{"id":"dataset:ega:egas00001003547","accession":"ega:EGAS00001003547","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001003547","title":"Germline variants collaborate with somatic mutations and initiate and/or drive disease in primary myelodysplastic syndrome (MDS) and therapy-related myeloid neoplasms (t-MN)","alternate_titles":[],"description":"Therapy-related myeloid neoplasms (T-MN) are poorly characterized secondary hematological malignancies following chemotherapy/radiotherapy exposure. 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Although the somatic mutation frequency was similar between T-MN and P-MDS patients (93% in both groups), the pattern was distinct.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Myelodysplastic Syndrome\"); description-level mentions were not accepted. EGA study_type: Cancer Genomics. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Myelodysplastic_Syndrome","name":"Myelodysplastic Syndrome","kind":"Disorder","source_path":"kb/disorders/Myelodysplastic_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myelodysplastic_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Myelodysplastic_Syndrome.html#dataset-ega-egas00001003547"}],"context_names":["Myelodysplastic Syndrome"],"disease_names":["Myelodysplastic Syndrome"],"disease_name":"Myelodysplastic Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Myelodysplastic_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myelodysplastic_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Myelodysplastic_Syndrome.html#dataset-ega-egas00001003547"]},{"id":"dataset:ega:egas00001003568","accession":"ega:EGAS00001003568","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001003568","title":"Multi-region sequencing of metastatic colorectal cancer","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["WES"],"data_type_labels":["Whole exome sequencing"],"data_type_label":"Whole exome sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Metastatic Colorectal Cancer\"); description-level mentions were not accepted. EGA study_type: Exome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Colon_Adenocarcinoma","name":"Colon Adenocarcinoma","kind":"Disorder","source_path":"kb/disorders/Colon_Adenocarcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Colon_Adenocarcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Colon_Adenocarcinoma.html#dataset-ega-egas00001003568"}],"context_names":["Colon Adenocarcinoma"],"disease_names":["Colon Adenocarcinoma"],"disease_name":"Colon Adenocarcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Colon_Adenocarcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Colon_Adenocarcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Colon_Adenocarcinoma.html#dataset-ega-egas00001003568"]},{"id":"dataset:ega:egas00001003573","accession":"ega:EGAS00001003573","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001003573","title":"Multi-Region WES of Metastatic Colorectal Cancer","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Metastatic Colorectal Cancer\"); description-level mentions were not accepted. EGA study_type: Cancer Genomics. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Colon_Adenocarcinoma","name":"Colon Adenocarcinoma","kind":"Disorder","source_path":"kb/disorders/Colon_Adenocarcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Colon_Adenocarcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Colon_Adenocarcinoma.html#dataset-ega-egas00001003573"}],"context_names":["Colon Adenocarcinoma"],"disease_names":["Colon Adenocarcinoma"],"disease_name":"Colon Adenocarcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Colon_Adenocarcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Colon_Adenocarcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Colon_Adenocarcinoma.html#dataset-ega-egas00001003573"]},{"id":"dataset:ega:egas00001003575","accession":"ega:EGAS00001003575","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001003575","title":"RNA-sequencing of adult T-cell leukemia/lymphoma samples","alternate_titles":[],"description":"Adult T-cell leukemia/lymphoma (ATL) is a highly aggressive hematological malignancy derived from mature CD4+ T-lymphocytes. 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EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Adult_T_Cell_Leukemia_Lymphoma","name":"Adult T-Cell Leukemia/Lymphoma","kind":"Disorder","source_path":"kb/disorders/Adult_T_Cell_Leukemia_Lymphoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Adult_T_Cell_Leukemia_Lymphoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Adult_T-Cell_Leukemia_Lymphoma.html#dataset-ega-egas00001003575"}],"context_names":["Adult T-Cell Leukemia/Lymphoma"],"disease_names":["Adult T-Cell Leukemia/Lymphoma"],"disease_name":"Adult T-Cell Leukemia/Lymphoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Adult_T_Cell_Leukemia_Lymphoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Adult_T_Cell_Leukemia_Lymphoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Adult_T-Cell_Leukemia_Lymphoma.html#dataset-ega-egas00001003575"]},{"id":"dataset:ega:egas00001003580","accession":"ega:EGAS00001003580","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001003580","title":"Single Cell Dissection of Nasopharyngeal Carcinoma","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Nasopharyngeal Carcinoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Nasopharyngeal_Carcinoma","name":"Nasopharyngeal Carcinoma","kind":"Disorder","source_path":"kb/disorders/Nasopharyngeal_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Nasopharyngeal_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Nasopharyngeal_Carcinoma.html#dataset-ega-egas00001003580"}],"context_names":["Nasopharyngeal Carcinoma"],"disease_names":["Nasopharyngeal Carcinoma"],"disease_name":"Nasopharyngeal Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Nasopharyngeal_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Nasopharyngeal_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Nasopharyngeal_Carcinoma.html#dataset-ega-egas00001003580"]},{"id":"dataset:ega:egas00001003581","accession":"ega:EGAS00001003581","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001003581","title":"Single Cell Dissection of Nasopharyngeal Carcinoma","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Nasopharyngeal Carcinoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Nasopharyngeal_Carcinoma","name":"Nasopharyngeal Carcinoma","kind":"Disorder","source_path":"kb/disorders/Nasopharyngeal_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Nasopharyngeal_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Nasopharyngeal_Carcinoma.html#dataset-ega-egas00001003581"}],"context_names":["Nasopharyngeal Carcinoma"],"disease_names":["Nasopharyngeal Carcinoma"],"disease_name":"Nasopharyngeal Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Nasopharyngeal_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Nasopharyngeal_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Nasopharyngeal_Carcinoma.html#dataset-ega-egas00001003581"]},{"id":"dataset:ega:egas00001003597","accession":"ega:EGAS00001003597","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001003597","title":"Genetic landscape of Waldenstrom macroglobulinemia","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Waldenstrom Macroglobulinemia\"); description-level mentions were not accepted. EGA study_type: Cancer Genomics. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Waldenstrom_Macroglobulinemia","name":"Waldenstrom Macroglobulinemia","kind":"Disorder","source_path":"kb/disorders/Waldenstrom_Macroglobulinemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Waldenstrom_Macroglobulinemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Waldenstrom_Macroglobulinemia.html#dataset-ega-egas00001003597"}],"context_names":["Waldenstrom Macroglobulinemia"],"disease_names":["Waldenstrom Macroglobulinemia"],"disease_name":"Waldenstrom Macroglobulinemia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Waldenstrom_Macroglobulinemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Waldenstrom_Macroglobulinemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Waldenstrom_Macroglobulinemia.html#dataset-ega-egas00001003597"]},{"id":"dataset:ega:egas00001003598","accession":"ega:EGAS00001003598","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001003598","title":"Single cell transcriptomic and genomic profiling of carcinogenesis in patients with familial adenomatous polyposis","alternate_titles":[],"description":"Familial Adenomatous Polyposis (FAP) is characterized by hundreds to thousands of adenocarcinomas at different evolutional stages in the colon and rectum. Much effort has been made to illuminate the key genomic alterations that facilitate the transition from adenoma to carcinoma. However, the strong heterogeneity of the tumors may hamper these efforts. Here, by sequencing matched adjacent normal tissues, adenomas at different stages and carcinomas from the same patient, we precisely traced the process of colorectal carcinogenesis.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Familial Adenomatous Polyposis\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Familial_Adenomatous_Polyposis","name":"Familial Adenomatous Polyposis","kind":"Disorder","source_path":"kb/disorders/Familial_Adenomatous_Polyposis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Familial_Adenomatous_Polyposis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Familial_Adenomatous_Polyposis.html#dataset-ega-egas00001003598"}],"context_names":["Familial Adenomatous Polyposis"],"disease_names":["Familial Adenomatous Polyposis"],"disease_name":"Familial Adenomatous Polyposis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Familial_Adenomatous_Polyposis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Familial_Adenomatous_Polyposis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Familial_Adenomatous_Polyposis.html#dataset-ega-egas00001003598"]},{"id":"dataset:ega:egas00001003603","accession":"ega:EGAS00001003603","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001003603","title":"Genetic and expression landscape of Waldenstrom macroglobulinemia","alternate_titles":[],"description":"Exome analyses for the identification of somatic mutation in Waldenstrom macroglobulinemia by comparison of tumor and CD3+(germ line control) population in 16 patients. transcription profiling of a series of Waldenstrom macroglobulinemia samples","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Waldenstrom Macroglobulinemia\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Waldenstrom_Macroglobulinemia","name":"Waldenstrom Macroglobulinemia","kind":"Disorder","source_path":"kb/disorders/Waldenstrom_Macroglobulinemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Waldenstrom_Macroglobulinemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Waldenstrom_Macroglobulinemia.html#dataset-ega-egas00001003603"}],"context_names":["Waldenstrom Macroglobulinemia"],"disease_names":["Waldenstrom Macroglobulinemia"],"disease_name":"Waldenstrom Macroglobulinemia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Waldenstrom_Macroglobulinemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Waldenstrom_Macroglobulinemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Waldenstrom_Macroglobulinemia.html#dataset-ega-egas00001003603"]},{"id":"dataset:ega:egas00001003605","accession":"ega:EGAS00001003605","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001003605","title":"A Phase II Trial of High Dose Interleukin-2 and Multi-site Stereotactic Ablative Radiotherapy for Patients with Metastatic Renal Cell Carcinoma","alternate_titles":[],"description":"Immune-based therapies have improved outcomes for metastatic renal cell carcinoma (mRCC) but there is still a significant margin for improvement. Here, we report the results of a phase II trial combining high dose Interleukin-2 (HD-IL-2) with stereotactic ablative body radiotherapy (SAbR) for patients with metastatic renal cell carcinoma.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Metastatic Renal Cell Carcinoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Renal_Cell_Carcinoma","name":"Renal Cell Carcinoma","kind":"Disorder","source_path":"kb/disorders/Renal_Cell_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Renal_Cell_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Renal_Cell_Carcinoma.html#dataset-ega-egas00001003605"}],"context_names":["Renal Cell Carcinoma"],"disease_names":["Renal Cell Carcinoma"],"disease_name":"Renal Cell Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Renal_Cell_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Renal_Cell_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Renal_Cell_Carcinoma.html#dataset-ega-egas00001003605"]},{"id":"dataset:ega:egas00001003618","accession":"ega:EGAS00001003618","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001003618","title":"Early-onset autoimmune hemolytic anemia study","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["WES"],"data_type_labels":["Whole exome sequencing"],"data_type_label":"Whole exome sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Autoimmune Hemolytic Anemia\"); description-level mentions were not accepted. EGA study_type: Exome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Autoimmune_Hemolytic_Anemia","name":"Autoimmune Hemolytic Anemia","kind":"Disorder","source_path":"kb/disorders/Autoimmune_Hemolytic_Anemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autoimmune_Hemolytic_Anemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autoimmune_Hemolytic_Anemia.html#dataset-ega-egas00001003618"}],"context_names":["Autoimmune Hemolytic Anemia"],"disease_names":["Autoimmune Hemolytic Anemia"],"disease_name":"Autoimmune Hemolytic Anemia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Autoimmune_Hemolytic_Anemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autoimmune_Hemolytic_Anemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Autoimmune_Hemolytic_Anemia.html#dataset-ega-egas00001003618"]},{"id":"dataset:ega:egas00001003658","accession":"ega:EGAS00001003658","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001003658","title":"Epitope-linked Ig-seq of self-reactive plasma cells in celiac disease","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Celiac Disease\"); description-level mentions were not accepted. EGA study_type: Transcriptome Analysis. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Celiac_Disease","name":"Celiac Disease","kind":"Disorder","source_path":"kb/disorders/Celiac_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Celiac_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Celiac_Disease.html#dataset-ega-egas00001003658"}],"context_names":["Celiac Disease"],"disease_names":["Celiac Disease"],"disease_name":"Celiac Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Celiac_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Celiac_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Celiac_Disease.html#dataset-ega-egas00001003658"]},{"id":"dataset:ega:egas00001003662","accession":"ega:EGAS00001003662","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001003662","title":"Combined genetic and transcriptome analysis of patients with Systemic Lupus Erythematosus (SLE)","alternate_titles":[],"description":"A comprehensive profiling of the genomic architecture of Systemic Lupus Erythematosus (SLE) by combining genetic and transscriptomic analysis by RNA-seq.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Systemic Lupus Erythematosus\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Systemic_Lupus_Erythematosus","name":"Systemic Lupus Erythematosus","kind":"Disorder","source_path":"kb/disorders/Systemic_Lupus_Erythematosus.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Systemic_Lupus_Erythematosus.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Systemic_Lupus_Erythematosus.html#dataset-ega-egas00001003662"}],"context_names":["Systemic Lupus Erythematosus"],"disease_names":["Systemic Lupus Erythematosus"],"disease_name":"Systemic Lupus Erythematosus","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Systemic_Lupus_Erythematosus.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Systemic_Lupus_Erythematosus.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Systemic_Lupus_Erythematosus.html#dataset-ega-egas00001003662"]},{"id":"dataset:ega:egas00001003689","accession":"ega:EGAS00001003689","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001003689","title":"Large-scale viral genome analysis identifies novel clinical associations between hepatitis B virus and chronically infected patients","alternate_titles":[],"description":"Despite the high global prevalence of chronic hepatitis B (CHB) infection, datasets covering the whole hepatitis B viral genome from large patient cohorts are lacking, greatly limiting our understanding of the viral genetic factors involved in this deadly disease. We performed deep sequencing of viral samples from patients chronically infected with HBV to investigate the association between viral genome variation and patients’ clinical characteristics. We discovered novel viral variants strongly associated with viral load and HBeAg status. Patients with viral variants C1817T and A1838G had viral loads nearly three orders of magnitude lower than patients without those variants.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:31324819"],"publication_contexts":[{"context_id":"disorder:Hepatitis_B","publication":"PMID:31324819"}],"publication":"PMID:31324819","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/31324819","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Hepatitis B\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Hepatitis_B","name":"Hepatitis B","kind":"Disorder","source_path":"kb/disorders/Hepatitis_B.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatitis_B.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hepatitis_B.html#dataset-ega-egas00001003689"}],"context_names":["Hepatitis B"],"disease_names":["Hepatitis B"],"disease_name":"Hepatitis B","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hepatitis_B.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatitis_B.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hepatitis_B.html#dataset-ega-egas00001003689"]},{"id":"dataset:ega:egas00001003715","accession":"ega:EGAS00001003715","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001003715","title":"Characterization of patient-derived xenograft models of myxoid liposarcoma either sentitive or resistant to trabectedin","alternate_titles":[],"description":"Two patient-derived xenograft model of myxoid liposarcoma one sensitive and one resistant to trabectedin. 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EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Liposarcoma","name":"Liposarcoma","kind":"Disorder","source_path":"kb/disorders/Liposarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Liposarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Liposarcoma.html#dataset-ega-egas00001003715"}],"context_names":["Liposarcoma"],"disease_names":["Liposarcoma"],"disease_name":"Liposarcoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Liposarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Liposarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Liposarcoma.html#dataset-ega-egas00001003715"]},{"id":"dataset:ega:egas00001003776","accession":"ega:EGAS00001003776","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001003776","title":"Targetable ERBB2 Mutations in Neurofibroma/Schwannoma Hybrid Nerve Sheath Tumors","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Neurofibroma\"); description-level mentions were not accepted. EGA study_type: Cancer Genomics. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.","European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Schwannoma\"); description-level mentions were not accepted. EGA study_type: Cancer Genomics. Controlled access -- data require a Data Access Agreement. 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The transcriptome profile of the small RNAs reflected disease state more robustly than mRNAs, even across brain regions which show very little pathology.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Epilepsy\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.","European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Temporal Lobe Epilepsy\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Epilepsy","name":"Epilepsy","kind":"Disorder","source_path":"kb/disorders/Epilepsy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Epilepsy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Epilepsy.html#dataset-ega-egas00001003922"},{"id":"disorder:Temporal_Lobe_Epilepsy","name":"Temporal Lobe Epilepsy","kind":"Disorder","source_path":"kb/disorders/Temporal_Lobe_Epilepsy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Temporal_Lobe_Epilepsy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Temporal_Lobe_Epilepsy.html#dataset-ega-egas00001003922"}],"context_names":["Epilepsy","Temporal Lobe Epilepsy"],"disease_names":["Epilepsy","Temporal Lobe Epilepsy"],"disease_name":"Epilepsy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Epilepsy.yaml","kb/disorders/Temporal_Lobe_Epilepsy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Epilepsy.yaml","https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Temporal_Lobe_Epilepsy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Epilepsy.html#dataset-ega-egas00001003922","https://dismech.monarchinitiative.org/pages/disorders/Temporal_Lobe_Epilepsy.html#dataset-ega-egas00001003922"]},{"id":"dataset:ega:egas00001003962","accession":"ega:EGAS00001003962","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001003962","title":"Breast implant-associated anaplastic large cell lymphoma shallow whole genome sequencing for copy number analysis and Whole exome sequencing data.","alternate_titles":[],"description":"Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) shallow whole genome sequencing of 29 BIA-ALCL patients for copy number analysis and 24 Alk-negative ALCL samples as control cohort. 7 Whole exome sequencing BIA-ALCL samples.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:32898861"],"publication_contexts":[{"context_id":"disorder:Anaplastic_Large_Cell_Lymphoma","publication":"PMID:32898861"},{"context_id":"disorder:Breast_Implant_Associated_Anaplastic_Large_Cell_Lymphoma","publication":"PMID:32898861"}],"publication":"PMID:32898861","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32898861","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Anaplastic Large Cell Lymphoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.","European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Breast Implant-Associated Anaplastic Large Cell Lymphoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Anaplastic_Large_Cell_Lymphoma","name":"Anaplastic Large Cell Lymphoma","kind":"Disorder","source_path":"kb/disorders/Anaplastic_Large_Cell_Lymphoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Anaplastic_Large_Cell_Lymphoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Anaplastic_Large_Cell_Lymphoma.html#dataset-ega-egas00001003962"},{"id":"disorder:Breast_Implant_Associated_Anaplastic_Large_Cell_Lymphoma","name":"Breast Implant-Associated Anaplastic Large Cell Lymphoma","kind":"Disorder","source_path":"kb/disorders/Breast_Implant_Associated_Anaplastic_Large_Cell_Lymphoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Breast_Implant_Associated_Anaplastic_Large_Cell_Lymphoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Breast_Implant-Associated_Anaplastic_Large_Cell_Lymphoma.html#dataset-ega-egas00001003962"}],"context_names":["Anaplastic Large Cell Lymphoma","Breast Implant-Associated Anaplastic Large Cell Lymphoma"],"disease_names":["Anaplastic Large Cell Lymphoma","Breast Implant-Associated Anaplastic Large Cell Lymphoma"],"disease_name":"Anaplastic Large Cell Lymphoma","same_context_model_ids":["model:kb/disorders/Anaplastic_Large_Cell_Lymphoma.yaml:Dominant-Negative STAT3 in Karpas 299 and SU-DHL-1 Cells"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Anaplastic_Large_Cell_Lymphoma.yaml","kb/disorders/Breast_Implant_Associated_Anaplastic_Large_Cell_Lymphoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Anaplastic_Large_Cell_Lymphoma.yaml","https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Breast_Implant_Associated_Anaplastic_Large_Cell_Lymphoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Anaplastic_Large_Cell_Lymphoma.html#dataset-ega-egas00001003962","https://dismech.monarchinitiative.org/pages/disorders/Breast_Implant-Associated_Anaplastic_Large_Cell_Lymphoma.html#dataset-ega-egas00001003962"]},{"id":"dataset:ega:egas00001004012","accession":"ega:EGAS00001004012","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001004012","title":"Familial adult myoclonic epilepsy in Sri Lankan and Indian families","alternate_titles":[],"description":"Familial adult myoclonic epilepsy 1 (FAME1), first recognised in Japanese families, was recently shown to be caused by a TTTCA repeat insertion in intron 4 of SAMD12 on chromosome 8. We performed whole genome sequencing on two families with FAME, one of Sri Lankan origin and the other of Indian origin, and identified a TTTCA repeat insertion in SAMD12 in both families. Haplotype analysis revealed that both families shared the same core ancestral haplotype reported in Japanese and Chinese families with FAME1. Mutation dating, based on the length of shared haplotypes, estimated the age of the ancestral haplotype to be approximately 670 generations, or 17,000 years old.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Epilepsy\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Epilepsy","name":"Epilepsy","kind":"Disorder","source_path":"kb/disorders/Epilepsy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Epilepsy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Epilepsy.html#dataset-ega-egas00001004012"}],"context_names":["Epilepsy"],"disease_names":["Epilepsy"],"disease_name":"Epilepsy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Epilepsy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Epilepsy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Epilepsy.html#dataset-ega-egas00001004012"]},{"id":"dataset:ega:egas00001004038","accession":"ega:EGAS00001004038","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001004038","title":"Familial multinodular goitre and schwannomatosis","alternate_titles":[],"description":"Whole exome sequencing of a kindred with early-onset MNG and schwannomatosis with a germline pathogenic variants in DGCR8. MiRNA profiles of four tissue types were compared, and sequencing of MiRNA, pre-miRNA and mRNA was performed in a subset of 9 schwannomas, four of which harbor DGCR8-E518K.The variant identified is a somatic hotspot in WT and has been identified in two PTCs. Copy number loss of chromosome 22q, leading to loss of heterozygosity at the c.1552G>A;p.E518K locus, was found in all 13 samples harboring c.1552G>A;p.E518K. miRNA profiling of PTC, MNG, schwannomas and WT revealed a common profile among E518K hemizygous tumors.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Schwannomatosis\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Schwannomatosis","name":"Schwannomatosis","kind":"Disorder","source_path":"kb/disorders/Schwannomatosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Schwannomatosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Schwannomatosis.html#dataset-ega-egas00001004038"}],"context_names":["Schwannomatosis"],"disease_names":["Schwannomatosis"],"disease_name":"Schwannomatosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Schwannomatosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Schwannomatosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Schwannomatosis.html#dataset-ega-egas00001004038"]},{"id":"dataset:ega:egas00001004101","accession":"ega:EGAS00001004101","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001004101","title":"The genomic landscape of metastatic papillary thyroid carcinoma and novel biomarkers for predicting distant metastasis","alternate_titles":[],"description":"Papillary thyroid carcinoma (PTC) is the most common malignancy of the thyroid gland with arelatively high cure rate. Distant metastasis (DM) of PTC is uncommon, but when it occurs, itsignificantly decreases the survival of PTC patients. However, the molecular mechanisms of DMin PTCs have not been systematically studied. We performed whole exome sequencing andGeneseeqPrime (425 genes) panel sequencing of the primary tumor, plasma and matched whiteblood cell samples from 20 PTCs with DM and 46 PTCs without DM. We identified somaticmutations, gene fusions and copy number alterations and analyzed their relationships with DM ofPTCs.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Papillary Thyroid Carcinoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Papillary_Thyroid_Carcinoma","name":"Papillary Thyroid Carcinoma","kind":"Disorder","source_path":"kb/disorders/Papillary_Thyroid_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Papillary_Thyroid_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Papillary_Thyroid_Carcinoma.html#dataset-ega-egas00001004101"}],"context_names":["Papillary Thyroid Carcinoma"],"disease_names":["Papillary Thyroid Carcinoma"],"disease_name":"Papillary Thyroid Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Papillary_Thyroid_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Papillary_Thyroid_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Papillary_Thyroid_Carcinoma.html#dataset-ega-egas00001004101"]},{"id":"dataset:ega:egas00001004113","accession":"ega:EGAS00001004113","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001004113","title":"Lenalidomide Resistance in del(5q) Myelodysplastic Syndrome Follows Loss of RUNX1/TP53-mediated Megakaryocytic Differentiation","alternate_titles":[],"description":"Interstitial deletion of the long arm of chromosome 5 (del(5q)) is the commonest structural genomic variant in myelodysplastic syndromes (MDS). Lenalidomide (LEN) is the treatment of choice for patients with del(5q) MDS, but half of the responding patients become resistant within two years. TP53 mutations are detected in ~20% of patients who become resistant to LEN. Our data show that patients who become resistant to LEN harbor either TP53 or RUNX1 mutations or loss of RUNX1 expression.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Myelodysplastic Syndrome\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Myelodysplastic_Syndrome","name":"Myelodysplastic Syndrome","kind":"Disorder","source_path":"kb/disorders/Myelodysplastic_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myelodysplastic_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Myelodysplastic_Syndrome.html#dataset-ega-egas00001004113"}],"context_names":["Myelodysplastic Syndrome"],"disease_names":["Myelodysplastic Syndrome"],"disease_name":"Myelodysplastic Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Myelodysplastic_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myelodysplastic_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Myelodysplastic_Syndrome.html#dataset-ega-egas00001004113"]},{"id":"dataset:ega:egas00001004152","accession":"ega:EGAS00001004152","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001004152","title":"Transcriptomic signatures of CD4+ T cells from visceral leishmaniasis (VL) patients","alternate_titles":[],"description":"Bulk RNA-sequencing was performed on CD4+ T cells isolated from the blood of visceral leishmaniasis patients (n = 12) and endemic controls (EC; n = 12). CD4+ T cells were obtained by magnetic-activated cell sorting (MACS). Alterations in the transcripts of T helper (Th) cells during infection were identified.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Leishmaniasis\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Leishmaniasis","name":"Leishmaniasis","kind":"Disorder","source_path":"kb/disorders/Leishmaniasis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Leishmaniasis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Leishmaniasis.html#dataset-ega-egas00001004152"}],"context_names":["Leishmaniasis"],"disease_names":["Leishmaniasis"],"disease_name":"Leishmaniasis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Leishmaniasis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Leishmaniasis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Leishmaniasis.html#dataset-ega-egas00001004152"]},{"id":"dataset:ega:egas00001004158","accession":"ega:EGAS00001004158","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001004158","title":"Molecular determinants for sensitivity to pazopanib in leiomyosarcoma, synovial sarcoma, and angiosarcoma.","alternate_titles":[],"description":"Pazopanib is a tyrosine kinase inhibitor with highest activity against VEGFR1 (FLT1) and VEGFR2 (KDR) along with other targets including VEGFR3, PDGFRa, PDGFRb, cKIT, FGFR1, FGFR3, FGFR4, FAK, ABL1, JNK1, Tie-2, Met, IGF1R, and EGFR (Lee, Jones, and Huang Signal Transduct Target Ther 2019; 4:16). Its initial activity in soft tissue sarcoma (STS) was described by Sleijfer et al. (2009) where a high proportion of leiomyosarcoma (LMS) (44%) and synovial sarcoma (49%) patients remained without progression at 12 weeks.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Angiosarcoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.","European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Leiomyosarcoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.","European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Synovial Sarcoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Angiosarcoma","name":"Angiosarcoma","kind":"Disorder","source_path":"kb/disorders/Angiosarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Angiosarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Angiosarcoma.html#dataset-ega-egas00001004158"},{"id":"disorder:Leiomyosarcoma","name":"Leiomyosarcoma","kind":"Disorder","source_path":"kb/disorders/Leiomyosarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Leiomyosarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Leiomyosarcoma.html#dataset-ega-egas00001004158"},{"id":"disorder:Synovial_Sarcoma","name":"Synovial Sarcoma","kind":"Disorder","source_path":"kb/disorders/Synovial_Sarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Synovial_Sarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Synovial_Sarcoma.html#dataset-ega-egas00001004158"}],"context_names":["Angiosarcoma","Leiomyosarcoma","Synovial Sarcoma"],"disease_names":["Angiosarcoma","Leiomyosarcoma","Synovial Sarcoma"],"disease_name":"Angiosarcoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Angiosarcoma.yaml","kb/disorders/Leiomyosarcoma.yaml","kb/disorders/Synovial_Sarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Angiosarcoma.yaml","https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Leiomyosarcoma.yaml","https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Synovial_Sarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Angiosarcoma.html#dataset-ega-egas00001004158","https://dismech.monarchinitiative.org/pages/disorders/Leiomyosarcoma.html#dataset-ega-egas00001004158","https://dismech.monarchinitiative.org/pages/disorders/Synovial_Sarcoma.html#dataset-ega-egas00001004158"]},{"id":"dataset:ega:egas00001004189","accession":"ega:EGAS00001004189","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001004189","title":"Integrative molecular analysis of pediatric Anaplastic large cell lymphoma reveals subtypes with distinct immune suppression signatures.","alternate_titles":[],"description":"Anaplastic large cell lymphoma (ALCL) is a peripheral T-cell lymphoma accounting for 10–15% of all childhood lymphomas. While more than 90% of the ALCL cases contain ALK-rearrangement, these tumors possess significant inter-tumor molecular heterogeneity that contributes to distinct morphologic differences and clinical impact. To gain insight into the molecular heterogeneity within ALK+ ALCL, we performed whole-exome sequencing, RNA-sequencing, and methylome analysis of 42 primary pediatric ALK+ ALCL patients. Our data showed that ALK+ALCLs was subclassified into two subtypes based on ALK gene expression, methylation profiles, and somatic mutation patterns.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Anaplastic Large Cell Lymphoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Anaplastic_Large_Cell_Lymphoma","name":"Anaplastic Large Cell Lymphoma","kind":"Disorder","source_path":"kb/disorders/Anaplastic_Large_Cell_Lymphoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Anaplastic_Large_Cell_Lymphoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Anaplastic_Large_Cell_Lymphoma.html#dataset-ega-egas00001004189"}],"context_names":["Anaplastic Large Cell Lymphoma"],"disease_names":["Anaplastic Large Cell Lymphoma"],"disease_name":"Anaplastic Large Cell Lymphoma","same_context_model_ids":["model:kb/disorders/Anaplastic_Large_Cell_Lymphoma.yaml:Dominant-Negative STAT3 in Karpas 299 and SU-DHL-1 Cells"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Anaplastic_Large_Cell_Lymphoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Anaplastic_Large_Cell_Lymphoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Anaplastic_Large_Cell_Lymphoma.html#dataset-ega-egas00001004189"]},{"id":"dataset:ega:egas00001004208","accession":"ega:EGAS00001004208","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001004208","title":"Pancreatic tropism of metastatic renal cell carcinoma","alternate_titles":[],"description":"Renal cell carcinoma (RCC) is characterized by a particularly broad metastatic swath, and enigmatically, when the pancreas is a destination, the disease is associated with improved survival. Intrigued by this observation, we sought to characterize the clinical behavior, therapeutic implications, and underlying biology. While pancreatic metastases (PM) are infrequent, we identified 31 patients across two institutional cohorts and show that improved survival is independent of established prognostic variables, that these tumors are exquisitely sensitive to anti-angiogenic agents and resistant to immune checkpoint inhibitors (ICI), and that they are characterized by a distinctive biology.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Metastatic Renal Cell Carcinoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Renal_Cell_Carcinoma","name":"Renal Cell Carcinoma","kind":"Disorder","source_path":"kb/disorders/Renal_Cell_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Renal_Cell_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Renal_Cell_Carcinoma.html#dataset-ega-egas00001004208"}],"context_names":["Renal Cell Carcinoma"],"disease_names":["Renal Cell Carcinoma"],"disease_name":"Renal Cell Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Renal_Cell_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Renal_Cell_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Renal_Cell_Carcinoma.html#dataset-ega-egas00001004208"]},{"id":"dataset:ega:egas00001004214","accession":"ega:EGAS00001004214","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001004214","title":"Analysis of exonic somatic variants in light-chain amyloidosis (ALA) and ALA concomitant with multiple myeloma","alternate_titles":[],"description":"We aim to provide the very first insight into ALA+MM molecular profiles and compare the results with ALA and with MM. Our detailed study of ALA and ALA+MM represents an important step towards improved understanding of their genetic and transcriptomic background, which is a prerequisite for development of optimal treatment strategies in the future.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Amyloidosis\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Amyloidosis","name":"Amyloidosis","kind":"Disorder","source_path":"kb/disorders/Amyloidosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Amyloidosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Amyloidosis.html#dataset-ega-egas00001004214"}],"context_names":["Amyloidosis"],"disease_names":["Amyloidosis"],"disease_name":"Amyloidosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Amyloidosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Amyloidosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Amyloidosis.html#dataset-ega-egas00001004214"]},{"id":"dataset:ega:egas00001004315","accession":"ega:EGAS00001004315","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001004315","title":"Enhancer-gene rewiring in the pathogenesis of Quebec Platelet Disorder","alternate_titles":[],"description":"Controlled-access raw sequencing data from the study that established enhancer adoption as the QPD mechanism: ChIP-seq for H3K27ac, H3K4me2, H3K36me3, H3K27me3 and CTCF, RNA-seq, and 4C-seq, generated in cultured megakaryocytes from QPD participants and unaffected controls.","alternate_descriptions":[],"data_types":["MULTI_OMICS"],"data_type_labels":["Multi Omics"],"data_type_label":"Multi Omics","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:32663239"],"publication_contexts":[{"context_id":"disorder:Quebec_Platelet_Disorder","publication":"PMID:32663239"}],"publication":"PMID:32663239","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32663239","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Controlled access through the European Genome-phenome Archive; no data files are mirrored into this repository. The accession is recorded from the publication rather than resolved by `just verify-datasets`, which does not cache EGA records."],"contexts":[{"id":"disorder:Quebec_Platelet_Disorder","name":"Quebec Platelet Disorder","kind":"Disorder","source_path":"kb/disorders/Quebec_Platelet_Disorder.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Quebec_Platelet_Disorder.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Quebec_Platelet_Disorder.html#dataset-ega-egas00001004315"}],"context_names":["Quebec Platelet Disorder"],"disease_names":["Quebec Platelet Disorder"],"disease_name":"Quebec Platelet Disorder","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Quebec_Platelet_Disorder.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Quebec_Platelet_Disorder.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Quebec_Platelet_Disorder.html#dataset-ega-egas00001004315"]},{"id":"dataset:ega:egas00001004365","accession":"ega:EGAS00001004365","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001004365","title":"Candidate Gene Case Control Study of Human African Trypanosomiasis in the Democratic Republic of Congo","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Human African trypanosomiasis\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Human_African_Trypanosomiasis","name":"Human African trypanosomiasis","kind":"Disorder","source_path":"kb/disorders/Human_African_Trypanosomiasis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Human_African_Trypanosomiasis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Human_African_trypanosomiasis.html#dataset-ega-egas00001004365"}],"context_names":["Human African trypanosomiasis"],"disease_names":["Human African trypanosomiasis"],"disease_name":"Human African trypanosomiasis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Human_African_Trypanosomiasis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Human_African_Trypanosomiasis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Human_African_trypanosomiasis.html#dataset-ega-egas00001004365"]},{"id":"dataset:ega:egas00001004386","accession":"ega:EGAS00001004386","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001004386","title":"Bulk RNAseq gene expression of baseline tumors from metastatic urothelial bladder cancer patients (IMvigor210) and metastatic renal cell carcinoma (IMmotion150)","alternate_titles":[],"description":"We examined tumors from a large cohort of patients with metastatic urothelial bladder cancer (mUC) and metastatic renal cell carcinoma (mRCC) treated with an anti-PD-L1 agent (atezolizumab) and found that high tumor IL8 gene expression was associated with worse overall survival (OS). We further identified the tumoral immune presence based on Teff signature. We found that high tumor IL8 expression continued to be associated with worse OS even in inflamed tumors in mUC and mRCC.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Metastatic Renal Cell Carcinoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Renal_Cell_Carcinoma","name":"Renal Cell Carcinoma","kind":"Disorder","source_path":"kb/disorders/Renal_Cell_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Renal_Cell_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Renal_Cell_Carcinoma.html#dataset-ega-egas00001004386"}],"context_names":["Renal Cell Carcinoma"],"disease_names":["Renal Cell Carcinoma"],"disease_name":"Renal Cell Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Renal_Cell_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Renal_Cell_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Renal_Cell_Carcinoma.html#dataset-ega-egas00001004386"]},{"id":"dataset:ega:egas00001004429","accession":"ega:EGAS00001004429","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001004429","title":"The genomic landscape of primary cutaneous anaplastic large cell lymphoma (pcALCL)","alternate_titles":[],"description":"Primary cutaneous anaplastic large cell lymphoma (pcALCL) is the second most common variant of cutaneous T-cell lymphoma. We subjected tumor biopsies from patients with pcALCL to whole-genome sequencing, whole-exome sequencing and RNA-sequencing to investigate genomic alterations and deregulated gene expression in the disease.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Anaplastic Large Cell Lymphoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Anaplastic_Large_Cell_Lymphoma","name":"Anaplastic Large Cell Lymphoma","kind":"Disorder","source_path":"kb/disorders/Anaplastic_Large_Cell_Lymphoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Anaplastic_Large_Cell_Lymphoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Anaplastic_Large_Cell_Lymphoma.html#dataset-ega-egas00001004429"}],"context_names":["Anaplastic Large Cell Lymphoma"],"disease_names":["Anaplastic Large Cell Lymphoma"],"disease_name":"Anaplastic Large Cell Lymphoma","same_context_model_ids":["model:kb/disorders/Anaplastic_Large_Cell_Lymphoma.yaml:Dominant-Negative STAT3 in Karpas 299 and SU-DHL-1 Cells"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Anaplastic_Large_Cell_Lymphoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Anaplastic_Large_Cell_Lymphoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Anaplastic_Large_Cell_Lymphoma.html#dataset-ega-egas00001004429"]},{"id":"dataset:ega:egas00001004439","accession":"ega:EGAS00001004439","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001004439","title":"Patient-derived organoids as a novel tool to study cervical cancer","alternate_titles":[],"description":"Cervical cancer is the most prevalent gynecological malignancy worldwide, often caused by infection with a high-risk human papillomavirus. Currently, there are only limited number of human-derived culture systems available that enable to study the viral infection for short-term. Here, we report on establishment of long-term human-derived organoid cultures from both healthy ecto- and endocervical epithelia that closely recapitulate the tissues of origin by maintaining the authentic histological and tissue-specific gene expression profiles.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Cervical Cancer\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Cervical_Cancer","name":"Cervical Cancer","kind":"Disorder","source_path":"kb/disorders/Cervical_Cancer.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cervical_Cancer.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cervical_Cancer.html#dataset-ega-egas00001004439"}],"context_names":["Cervical Cancer"],"disease_names":["Cervical Cancer"],"disease_name":"Cervical Cancer","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cervical_Cancer.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cervical_Cancer.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cervical_Cancer.html#dataset-ega-egas00001004439"]},{"id":"dataset:ega:egas00001004450","accession":"ega:EGAS00001004450","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001004450","title":"Suppressive granulocytes are an indicator of severe disease in COVID-19","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"COVID-19\"); description-level mentions were not accepted. EGA study_type: RNASeq. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:COVID-19","name":"COVID-19","kind":"Disorder","source_path":"kb/disorders/COVID-19.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/COVID-19.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/COVID-19.html#dataset-ega-egas00001004450"}],"context_names":["COVID-19"],"disease_names":["COVID-19"],"disease_name":"COVID-19","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/COVID-19.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/COVID-19.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/COVID-19.html#dataset-ega-egas00001004450"]},{"id":"dataset:ega:egas00001004468","accession":"ega:EGAS00001004468","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001004468","title":"A Single-Cell Atlas of the Multicellular Ecosystem of Primary and Metastatic Hepatocellular Carcinoma","alternate_titles":[],"description":"Hepatocellular carcinoma (HCC) represents a paradigm of the relation between tumor microenvironment (TME) and tumor development. 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We identified CD11b+ macrophages to be terminally differentiated tumor-associated macrophages (TAMs) and two distinct differentiation trajectories contribute to their accumulation.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Metastatic Hepatocellular Carcinoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Hepatocellular_Carcinoma","name":"Hepatocellular Carcinoma","kind":"Disorder","source_path":"kb/disorders/Hepatocellular_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatocellular_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hepatocellular_Carcinoma.html#dataset-ega-egas00001004468"}],"context_names":["Hepatocellular Carcinoma"],"disease_names":["Hepatocellular Carcinoma"],"disease_name":"Hepatocellular Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hepatocellular_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatocellular_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hepatocellular_Carcinoma.html#dataset-ega-egas00001004468"]},{"id":"dataset:ega:egas00001004474","accession":"ega:EGAS00001004474","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001004474","title":"Peripheral immunoprofiling of stratifies COVID-19 patients based on disease-specific neutrophil signatures","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"COVID-19\"); description-level mentions were not accepted. EGA study_type: RNASeq. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:COVID-19","name":"COVID-19","kind":"Disorder","source_path":"kb/disorders/COVID-19.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/COVID-19.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/COVID-19.html#dataset-ega-egas00001004474"}],"context_names":["COVID-19"],"disease_names":["COVID-19"],"disease_name":"COVID-19","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/COVID-19.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/COVID-19.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/COVID-19.html#dataset-ega-egas00001004474"]},{"id":"dataset:ega:egas00001004476","accession":"ega:EGAS00001004476","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001004476","title":"RNA sequencing of subchondral bone from patients that underwent a joint replacement surgery due to osteoarthritis.","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Osteoarthritis\"); description-level mentions were not accepted. 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EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Osteoarthritis","name":"Osteoarthritis","kind":"Disorder","source_path":"kb/disorders/Osteoarthritis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Osteoarthritis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Osteoarthritis.html#dataset-ega-egas00001004476"}],"context_names":["Osteoarthritis"],"disease_names":["Osteoarthritis"],"disease_name":"Osteoarthritis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Osteoarthritis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Osteoarthritis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Osteoarthritis.html#dataset-ega-egas00001004476"]},{"id":"dataset:ega:egas00001004481","accession":"ega:EGAS00001004481","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001004481","title":"Single-cell analysis of airway samples identifies immune cell activation correlating with COVID-19 disease severity","alternate_titles":[],"description":"To investigate the immune response and mechanisms associated with severe COVID-19, we performed single-cell RNA-seq on nasopharyngeal and bronchial samples from 19 clinically well-characterized patients with moderate or critical disease and from 5 healthy controls. 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EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Chondrosarcoma","name":"Chondrosarcoma","kind":"Disorder","source_path":"kb/disorders/Chondrosarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chondrosarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chondrosarcoma.html#dataset-ega-egas00001004585"}],"context_names":["Chondrosarcoma"],"disease_names":["Chondrosarcoma"],"disease_name":"Chondrosarcoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chondrosarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chondrosarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chondrosarcoma.html#dataset-ega-egas00001004585"]},{"id":"dataset:ega:egas00001004586","accession":"ega:EGAS00001004586","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001004586","title":"Cerebral organoid model reveals excessive proliferation of human caudal late interneuron progenitors in Tuberous Sclerosis Complex","alternate_titles":[],"description":"Although the intricate and prolonged development of the human brain critically distinguishes it from other mammals, our current understanding of neurodevelopmental diseases is largely based on work using animal models. Recent studies revealed that neural progenitors in the human brain are profoundly different from those found in rodent animal models. Moreover, post-mortem studies revealed extensive migration of interneurons into the late-gestational and post-natal human prefrontal cortex that does not occur in rodents.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Tuberous Sclerosis Complex\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Tuberous_Sclerosis_Complex","name":"Tuberous Sclerosis Complex","kind":"Disorder","source_path":"kb/disorders/Tuberous_Sclerosis_Complex.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Tuberous_Sclerosis_Complex.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Tuberous_Sclerosis_Complex.html#dataset-ega-egas00001004586"}],"context_names":["Tuberous Sclerosis Complex"],"disease_names":["Tuberous Sclerosis Complex"],"disease_name":"Tuberous Sclerosis Complex","same_context_model_ids":["model:kb/disorders/Tuberous_Sclerosis_Complex.yaml:CRISPR-engineered TSC2 conditional-biallelic human cortical spheroids","model:kb/disorders/Tuberous_Sclerosis_Complex.yaml:TSC human cerebral organoids with caudal late interneuron progenitor (CLIP) over-proliferation","model:kb/disorders/Tuberous_Sclerosis_Complex.yaml:TSC patient-derived neurovascular unit (iPSC blood-brain-barrier chip)"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Tuberous_Sclerosis_Complex.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Tuberous_Sclerosis_Complex.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Tuberous_Sclerosis_Complex.html#dataset-ega-egas00001004586"]},{"id":"dataset:ega:egas00001004596","accession":"ega:EGAS00001004596","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001004596","title":"A GWAS for cutaneous leishmaniasis in Brazil","alternate_titles":[],"description":"Our goal was to identify genetic risk factors for cutaneous leishmaniasis (CL) caused by Leishmania braziliensis. Genotyping 2066 CL cases and 2046 controls using Illumina HumanCoreExomeBeadChips provided data for 4,498,586 imputed single nucleotide variants (SNVs). Genome-wide association testing using linear mixed models took account of genetic diversity/ethnicity/admixture. Post-GWAS positional, expression quantitative trait locus (eQTL), and chromatin interaction mapping was performed in FUMA. Transcriptional data were compared between lesions and normal skin, and cytokines measured using flow cytometry and Bioplex assay.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Leishmaniasis\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Leishmaniasis","name":"Leishmaniasis","kind":"Disorder","source_path":"kb/disorders/Leishmaniasis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Leishmaniasis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Leishmaniasis.html#dataset-ega-egas00001004596"}],"context_names":["Leishmaniasis"],"disease_names":["Leishmaniasis"],"disease_name":"Leishmaniasis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Leishmaniasis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Leishmaniasis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Leishmaniasis.html#dataset-ega-egas00001004596"]},{"id":"dataset:ega:egas00001004609","accession":"ega:EGAS00001004609","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001004609","title":"Multiple neoplasia in a patient with Gitelman syndrome harboring germline monoallelic MUTYH mutation","alternate_titles":[],"description":"Gitelman syndrome is a rare, recessively-inherited disease characterized by chronic hypokalemia and hypomagnesemia as a result of defective electrolyte co-transport at the level of the distal convoluted tubule of the kidney. Here, we present the first report of a patient with Gitelman syndrome who developed multiple neoplasia including colorectal polyposis, synchronous colorectal cancers, recurrent breast fibroadenomata and a desmoid tumor. Whole exome sequencing confirmed germline compound heterozygous mutations of c.179C>T and c.1326C>G in SLC12A3, and in addition, identified a monoallelic germline c.934-2A>G splice site mutation in MUTYH.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Gitelman syndrome\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Gitelman_Syndrome","name":"Gitelman syndrome","kind":"Disorder","source_path":"kb/disorders/Gitelman_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Gitelman_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Gitelman_syndrome.html#dataset-ega-egas00001004609"}],"context_names":["Gitelman syndrome"],"disease_names":["Gitelman syndrome"],"disease_name":"Gitelman syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Gitelman_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Gitelman_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Gitelman_syndrome.html#dataset-ega-egas00001004609"]},{"id":"dataset:ega:egas00001004629","accession":"ega:EGAS00001004629","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001004629","title":"Hepatitis B virus integrations promote local and distant oncogenic driver alterations in hepatocarcinogenesis","alternate_titles":[],"description":"Infection by Hepatitis B Virus (HBV) is the main risk factor for Hepatocellular Carcinoma (HCC) worldwide. HBV can directly drive carcinogenesis through integrations in human genome. This integrative analysis of a French cohort of 190 patients mainly coming from Europe and Africa provides a deep characterization of HBV integrations, in relation with viral and host genomics and clinical features. Clonal HBV integrations directly contribute to HCC development through alterations of cancer driver genes, either at distance when co-localizing with copy number alterations, either locally through viral Enhancers.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Hepatitis B\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Hepatitis_B","name":"Hepatitis B","kind":"Disorder","source_path":"kb/disorders/Hepatitis_B.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatitis_B.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hepatitis_B.html#dataset-ega-egas00001004629"}],"context_names":["Hepatitis B"],"disease_names":["Hepatitis B"],"disease_name":"Hepatitis B","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hepatitis_B.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatitis_B.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hepatitis_B.html#dataset-ega-egas00001004629"]},{"id":"dataset:ega:egas00001004758","accession":"ega:EGAS00001004758","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001004758","title":"The transition from normal lung anatomy to minimal and established fibrosis in Idiopathic Pulmonary Fibrosis","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Idiopathic Pulmonary Fibrosis\"); description-level mentions were not accepted. EGA study_type: RNASeq. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Idiopathic_Pulmonary_Fibrosis","name":"Idiopathic Pulmonary Fibrosis","kind":"Disorder","source_path":"kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Idiopathic_Pulmonary_Fibrosis.html#dataset-ega-egas00001004758"}],"context_names":["Idiopathic Pulmonary Fibrosis"],"disease_names":["Idiopathic Pulmonary Fibrosis"],"disease_name":"Idiopathic Pulmonary Fibrosis","same_context_model_ids":["model:kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml:Immune-cell-free AT2-lineage and fibroblast organoids","model:kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml:Microengineered alveolar array lung-on-chip with breathing mechanics"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Idiopathic_Pulmonary_Fibrosis.html#dataset-ega-egas00001004758"]},{"id":"dataset:ega:egas00001004783","accession":"ega:EGAS00001004783","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001004783","title":"Rna-Seq Leiomyosarcoma subtypes","alternate_titles":[],"description":"Leiomyosarcomas (LMS) are genetically heterogeneous tumors differentiating along smooth muscle lines. Currently, LMS treatment is not informed by molecular subtyping and is associated with highly variable survival. While disease site continues to dictate clinical management, the contribution of genetic factors to LMS subtype, origins, and timing are unknown. Here we analyzed 70 genomes and 130 transcriptomes of LMS, including multiple tumor regions and paired metastases. Molecular profiling highlighted the extremely early origins of LMS. Three specific subtypes of LMS develop from distinct lineages of smooth muscle cells.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Leiomyosarcoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Leiomyosarcoma","name":"Leiomyosarcoma","kind":"Disorder","source_path":"kb/disorders/Leiomyosarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Leiomyosarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Leiomyosarcoma.html#dataset-ega-egas00001004783"}],"context_names":["Leiomyosarcoma"],"disease_names":["Leiomyosarcoma"],"disease_name":"Leiomyosarcoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Leiomyosarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Leiomyosarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Leiomyosarcoma.html#dataset-ega-egas00001004783"]},{"id":"dataset:ega:egas00001004793","accession":"ega:EGAS00001004793","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001004793","title":"Compound heterozygous variants in LAMC3 in association with posterior periventricular nodular heterotopia","alternate_titles":[],"description":"Periventricular nodular heterotopia is a malformation of cortical development characterized by nodules of abnormally migrated neurons.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Periventricular Nodular Heterotopia\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Periventricular_Nodular_Heterotopia","name":"Periventricular Nodular Heterotopia","kind":"Disorder","source_path":"kb/disorders/Periventricular_Nodular_Heterotopia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Periventricular_Nodular_Heterotopia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Periventricular_Nodular_Heterotopia.html#dataset-ega-egas00001004793"}],"context_names":["Periventricular Nodular Heterotopia"],"disease_names":["Periventricular Nodular Heterotopia"],"disease_name":"Periventricular Nodular Heterotopia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Periventricular_Nodular_Heterotopia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Periventricular_Nodular_Heterotopia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Periventricular_Nodular_Heterotopia.html#dataset-ega-egas00001004793"]},{"id":"dataset:ega:egas00001004827","accession":"ega:EGAS00001004827","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001004827","title":"Volasertib preclinical activity in high-risk hepatoblastoma","alternate_titles":[],"description":"Relapsed and metastatic hepatoblastoma represents an unmet clinical need with limited chemotherapy treatment options. In a chemical screen, we identified volasertib as an agent with in vitro activity, inhibiting hepatoblastoma cell growth while sparing normal hepatocytes. Volasertib targets PLK1 and prevents the progression of mitosis, resulting in eventual cell death. PLK1 is overexpressed in hepatoblastoma biopsies relative to normal liver tissue. As a potential therapeutic strategy, we tested the combination of volasertib and the relapse-related hepatoblastoma chemotherapeutic irinotecan.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Hepatoblastoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Hepatoblastoma","name":"Hepatoblastoma","kind":"Disorder","source_path":"kb/disorders/Hepatoblastoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatoblastoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hepatoblastoma.html#dataset-ega-egas00001004827"}],"context_names":["Hepatoblastoma"],"disease_names":["Hepatoblastoma"],"disease_name":"Hepatoblastoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hepatoblastoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatoblastoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hepatoblastoma.html#dataset-ega-egas00001004827"]},{"id":"dataset:ega:egas00001004886","accession":"ega:EGAS00001004886","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001004886","title":"mRNA and T cell receptor sequencing of patients with Pandemrix-associated narcolepsy type 1","alternate_titles":[],"description":"Increased risk of Narcolepsy type 1 (NT1) was reported among children and adolescents vaccinated with AS03-adjuvanted pandemic influenza A vaccine (H1N1; Pandemrix®). We hypothesized that viral T cell epitope(s) in Pandemrix mimicked self-epitope(s), and that recognition of these cross-reactive epitopes contributed to disease-specific autoimmunity. We demonstrate that pediatric, Pandemrix-associated NT1 patients had enhanced T-cell immunity against dominant T-cell epitopes of Pandemrix vaccine viral proteins neuraminidase (NA) and nucleoprotein (NP), and also responded against a self-epitope in brain-expressed protein-O-mannosyltransferase 1 (POMT1).","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Narcolepsy\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Narcolepsy","name":"Narcolepsy","kind":"Disorder","source_path":"kb/disorders/Narcolepsy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Narcolepsy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Narcolepsy.html#dataset-ega-egas00001004886"}],"context_names":["Narcolepsy"],"disease_names":["Narcolepsy"],"disease_name":"Narcolepsy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Narcolepsy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Narcolepsy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Narcolepsy.html#dataset-ega-egas00001004886"]},{"id":"dataset:ega:egas00001004899","accession":"ega:EGAS00001004899","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001004899","title":"Personalised therapy with MEK inhibition leads to a sustained complete response in an adolescent patient with a recurrent malignant peripheral nerve sheath tumor","alternate_titles":[],"description":"The prognosis of recurrent malignant peripheral nerve sheath tumors (MPNST) is dismal, with surgical resection being the only definitive salvage therapy. Treatment with chemo-radiation approaches has not significantly improved patient outcomes. Similarly, trials of therapies targeting MPNST genomic drivers have thus far been unsuccessful. Improved understanding of the molecular pathogenesis of MPNST indicates frequent activation of the mitogen activated protein kinase (MAPK) cell signaling pathway. MEK inhibitors have shown activity in preclinical studies; however, their clinical efficacy has not been reported to date.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Malignant Peripheral Nerve Sheath Tumor\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Malignant_Peripheral_Nerve_Sheath_Tumor","name":"Malignant Peripheral Nerve Sheath Tumor","kind":"Disorder","source_path":"kb/disorders/Malignant_Peripheral_Nerve_Sheath_Tumor.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Malignant_Peripheral_Nerve_Sheath_Tumor.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Malignant_Peripheral_Nerve_Sheath_Tumor.html#dataset-ega-egas00001004899"}],"context_names":["Malignant Peripheral Nerve Sheath Tumor"],"disease_names":["Malignant Peripheral Nerve Sheath Tumor"],"disease_name":"Malignant Peripheral Nerve Sheath Tumor","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Malignant_Peripheral_Nerve_Sheath_Tumor.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Malignant_Peripheral_Nerve_Sheath_Tumor.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Malignant_Peripheral_Nerve_Sheath_Tumor.html#dataset-ega-egas00001004899"]},{"id":"dataset:ega:egas00001004901","accession":"ega:EGAS00001004901","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001004901","title":"Total RNA-Sequencing of patient-derived xenograft models of myxoid liposarcoma","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Liposarcoma\"); description-level mentions were not accepted. EGA study_type: RNASeq. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Liposarcoma","name":"Liposarcoma","kind":"Disorder","source_path":"kb/disorders/Liposarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Liposarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Liposarcoma.html#dataset-ega-egas00001004901"}],"context_names":["Liposarcoma"],"disease_names":["Liposarcoma"],"disease_name":"Liposarcoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Liposarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Liposarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Liposarcoma.html#dataset-ega-egas00001004901"]},{"id":"dataset:ega:egas00001004908","accession":"ega:EGAS00001004908","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001004908","title":"Mutations in SKI in Shprintzen-Goldberg syndrome lead to attenuated TGFB responses through SKI stabilization","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Shprintzen-Goldberg Syndrome\"); description-level mentions were not accepted. EGA study_type: RNASeq. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Shprintzen-Goldberg_Syndrome","name":"Shprintzen-Goldberg Syndrome","kind":"Disorder","source_path":"kb/disorders/Shprintzen-Goldberg_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Shprintzen-Goldberg_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Shprintzen-Goldberg_Syndrome.html#dataset-ega-egas00001004908"}],"context_names":["Shprintzen-Goldberg Syndrome"],"disease_names":["Shprintzen-Goldberg Syndrome"],"disease_name":"Shprintzen-Goldberg Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Shprintzen-Goldberg_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Shprintzen-Goldberg_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Shprintzen-Goldberg_Syndrome.html#dataset-ega-egas00001004908"]},{"id":"dataset:ega:egas00001004927","accession":"ega:EGAS00001004927","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001004927","title":"Short and long-read sequencing of Brugada syndrome samples","alternate_titles":[],"description":"Genome-wide association studies (GWAS) are instrumental in identifying loci with an impact on human traits and disease. 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EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Brugada_Syndrome","name":"Brugada syndrome","kind":"Disorder","source_path":"kb/disorders/Brugada_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Brugada_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Brugada_syndrome.html#dataset-ega-egas00001004927"}],"context_names":["Brugada syndrome"],"disease_names":["Brugada syndrome"],"disease_name":"Brugada syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Brugada_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Brugada_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Brugada_syndrome.html#dataset-ega-egas00001004927"]},{"id":"dataset:ega:egas00001005000","accession":"ega:EGAS00001005000","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001005000","title":"single cell sequencing of resting and Influenza-stimulated mononcluear phagocytes of African and Europeans with varying degree of ex-vivo susceptibility to Influenza","alternate_titles":[],"description":"There is considerable inter-individual immunological and clinical variability upon influenza A virus (IAV) infection in humans; yet, the factors underlying such heterogeneity remain elusive. Here, using an ex vivo cellular model that captures natural variation in the transcriptional responses of monocytes to IAV, we find significant differences in viral mRNA levels between individuals of African and European ancestry. Using single cell analyses, we show that the overall number of cells that will ultimately become infected, rather than the amount of viral transcript expression per cell, is the main driver of the surprisingly higher IAV mRNA levels detected in European cells.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Influenza\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Influenza","name":"Influenza","kind":"Disorder","source_path":"kb/disorders/Influenza.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Influenza.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Influenza.html#dataset-ega-egas00001005000"}],"context_names":["Influenza"],"disease_names":["Influenza"],"disease_name":"Influenza","same_context_model_ids":["model:kb/disorders/Influenza.yaml:Immune-competent microvascularized lung-on-a-chip (IC-LOC) severe H1N1 model"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Influenza.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Influenza.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Influenza.html#dataset-ega-egas00001005000"]},{"id":"dataset:ega:egas00001005004","accession":"ega:EGAS00001005004","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001005004","title":"Fibromyalgia versus small fiber neuropathy: Diverse keratinocyte transcriptome signature","alternate_titles":[],"description":"We provide a diverse keratinocyte transcriptome signature between SFN and FMS patients, which may hint towards distinct pathomechanisms of small fiber sensitization and lay the basis for advanced diagnostics in both entities","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:33675632"],"publication_contexts":[{"context_id":"disorder:Fibromyalgia","publication":"PMID:33675632"}],"publication":"PMID:33675632","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/33675632","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Fibromyalgia\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Fibromyalgia","name":"Fibromyalgia","kind":"Disorder","source_path":"kb/disorders/Fibromyalgia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fibromyalgia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Fibromyalgia.html#dataset-ega-egas00001005004"}],"context_names":["Fibromyalgia"],"disease_names":["Fibromyalgia"],"disease_name":"Fibromyalgia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Fibromyalgia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fibromyalgia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Fibromyalgia.html#dataset-ega-egas00001005004"]},{"id":"dataset:ega:egas00001005006","accession":"ega:EGAS00001005006","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001005006","title":"Longitudinal single-cell RNA-seq data of metastatic ovarian cancer","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Metastatic Ovarian Cancer\"); description-level mentions were not accepted. EGA study_type: Transcriptome Analysis. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Ovarian_High-Grade_Serous_Carcinoma","name":"Ovarian High-Grade Serous Carcinoma","kind":"Disorder","source_path":"kb/disorders/Ovarian_High-Grade_Serous_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ovarian_High-Grade_Serous_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Ovarian_High-Grade_Serous_Carcinoma.html#dataset-ega-egas00001005006"}],"context_names":["Ovarian High-Grade Serous Carcinoma"],"disease_names":["Ovarian High-Grade Serous Carcinoma"],"disease_name":"Ovarian High-Grade Serous Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Ovarian_High-Grade_Serous_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ovarian_High-Grade_Serous_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Ovarian_High-Grade_Serous_Carcinoma.html#dataset-ega-egas00001005006"]},{"id":"dataset:ega:egas00001005010","accession":"ega:EGAS00001005010","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001005010","title":"Longitudinal single-cell RNA-seq data of metastatic ovarian cancer","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:35196078"],"publication_contexts":[{"context_id":"disorder:Ovarian_High-Grade_Serous_Carcinoma","publication":"PMID:35196078"}],"publication":"PMID:35196078","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35196078","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Metastatic Ovarian Cancer\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Ovarian_High-Grade_Serous_Carcinoma","name":"Ovarian High-Grade Serous Carcinoma","kind":"Disorder","source_path":"kb/disorders/Ovarian_High-Grade_Serous_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ovarian_High-Grade_Serous_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Ovarian_High-Grade_Serous_Carcinoma.html#dataset-ega-egas00001005010"}],"context_names":["Ovarian High-Grade Serous Carcinoma"],"disease_names":["Ovarian High-Grade Serous Carcinoma"],"disease_name":"Ovarian High-Grade Serous Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Ovarian_High-Grade_Serous_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ovarian_High-Grade_Serous_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Ovarian_High-Grade_Serous_Carcinoma.html#dataset-ega-egas00001005010"]},{"id":"dataset:ega:egas00001005028","accession":"ega:EGAS00001005028","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001005028","title":"Merkel cell polyomavirus-negative -Merkel cell carcinoma originating from in situ squamous cell carcinoma: a keratinocytic tumor with neuroendocrine differentiation","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Merkel Cell Carcinoma\"); description-level mentions were not accepted. EGA study_type: Cancer Genomics. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Merkel_Cell_Carcinoma","name":"Merkel Cell Carcinoma","kind":"Disorder","source_path":"kb/disorders/Merkel_Cell_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Merkel_Cell_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Merkel_Cell_Carcinoma.html#dataset-ega-egas00001005028"}],"context_names":["Merkel Cell Carcinoma"],"disease_names":["Merkel Cell Carcinoma"],"disease_name":"Merkel Cell Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Merkel_Cell_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Merkel_Cell_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Merkel_Cell_Carcinoma.html#dataset-ega-egas00001005028"]},{"id":"dataset:ega:egas00001005053","accession":"ega:EGAS00001005053","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001005053","title":"Hermansky-Pudlak syndrome type 1 causes impaired anti-microbial immunity  through a pathogenic lipid metabolism-mTOR circuit","alternate_titles":[],"description":"Mendelian diseases that present with immune-mediated disorders can provide insights into the molecular mechanisms that drive inflammation. Hermansky-Pudlak syndrome (HPS) types 1 and 4 are caused by defective vesicle trafficking involving the BLOC-3 complex. The presence of inflammatory complications such as Crohn’s disease-like inflammation and lung fibrosis in these patients remains enigmatic. Using mass cytometry we observe an augmented inflammatory monocyte compartment in HPS1 patient peripheral blood that may be associated with a TNF - and IL-1α-dominated cytokine dysregulation.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Hermansky-Pudlak Syndrome\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Hermansky_Pudlak_Syndrome","name":"Hermansky-Pudlak Syndrome","kind":"Disorder","source_path":"kb/disorders/Hermansky_Pudlak_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hermansky_Pudlak_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hermansky-Pudlak_Syndrome.html#dataset-ega-egas00001005053"}],"context_names":["Hermansky-Pudlak Syndrome"],"disease_names":["Hermansky-Pudlak Syndrome"],"disease_name":"Hermansky-Pudlak Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hermansky_Pudlak_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hermansky_Pudlak_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hermansky-Pudlak_Syndrome.html#dataset-ega-egas00001005053"]},{"id":"dataset:ega:egas00001005065","accession":"ega:EGAS00001005065","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001005065","title":"Genomic Landscape of Malignant Peripheral Nerve Sheath Tumor-like Melanoma","alternate_titles":[],"description":"Malignant peripheral nerve sheath tumor (MPNST)-like melanoma is a rare malignancy with overlapping characteristics of both neural sarcoma and melanoma. The genomics of MPNST-like melanoma have not been previously described. This study provides the results of whole exome and transcriptome sequencing analysis of 8 samples from 6 patients with confirmed diagnosis of MPNST-like melanoma. This study demonstrates that MPNST-like melanoma shares oncogenic alterations common to both cutaneous melanoma and MPNST, and also suggests that MPNST-like melanoma harbors unique genomic and transcriptomic alterations.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Malignant Peripheral Nerve Sheath Tumor\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Malignant_Peripheral_Nerve_Sheath_Tumor","name":"Malignant Peripheral Nerve Sheath Tumor","kind":"Disorder","source_path":"kb/disorders/Malignant_Peripheral_Nerve_Sheath_Tumor.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Malignant_Peripheral_Nerve_Sheath_Tumor.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Malignant_Peripheral_Nerve_Sheath_Tumor.html#dataset-ega-egas00001005065"}],"context_names":["Malignant Peripheral Nerve Sheath Tumor"],"disease_names":["Malignant Peripheral Nerve Sheath Tumor"],"disease_name":"Malignant Peripheral Nerve Sheath Tumor","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Malignant_Peripheral_Nerve_Sheath_Tumor.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Malignant_Peripheral_Nerve_Sheath_Tumor.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Malignant_Peripheral_Nerve_Sheath_Tumor.html#dataset-ega-egas00001005065"]},{"id":"dataset:ega:egas00001005066","accession":"ega:EGAS00001005066","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001005066","title":"Single-cell RNA-seq data from metastatic ovarian cancer for quality control study","alternate_titles":[],"description":"Quality control is a crucial preliminary step in any single-cell RNAseq experiment, where hard thresholds are commonly used. In order to develop a methodology for a more precise cell filtering in the early steps of a scRNAseq data analysis, we collected tissue samples before chemotherapy from 4 patients.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Metastatic Ovarian Cancer\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Ovarian_High-Grade_Serous_Carcinoma","name":"Ovarian High-Grade Serous Carcinoma","kind":"Disorder","source_path":"kb/disorders/Ovarian_High-Grade_Serous_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ovarian_High-Grade_Serous_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Ovarian_High-Grade_Serous_Carcinoma.html#dataset-ega-egas00001005066"}],"context_names":["Ovarian High-Grade Serous Carcinoma"],"disease_names":["Ovarian High-Grade Serous Carcinoma"],"disease_name":"Ovarian High-Grade Serous Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Ovarian_High-Grade_Serous_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ovarian_High-Grade_Serous_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Ovarian_High-Grade_Serous_Carcinoma.html#dataset-ega-egas00001005066"]},{"id":"dataset:ega:egas00001005081","accession":"ega:EGAS00001005081","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001005081","title":"Molecular analysis of inflammatory myofibroblastic tumor (WGS and WES)","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Inflammatory Myofibroblastic Tumor\"); description-level mentions were not accepted. EGA study_type: Cancer Genomics. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Inflammatory_Myofibroblastic_Tumor","name":"Inflammatory Myofibroblastic Tumor","kind":"Disorder","source_path":"kb/disorders/Inflammatory_Myofibroblastic_Tumor.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Inflammatory_Myofibroblastic_Tumor.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Inflammatory_Myofibroblastic_Tumor.html#dataset-ega-egas00001005081"}],"context_names":["Inflammatory Myofibroblastic Tumor"],"disease_names":["Inflammatory Myofibroblastic Tumor"],"disease_name":"Inflammatory Myofibroblastic Tumor","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Inflammatory_Myofibroblastic_Tumor.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Inflammatory_Myofibroblastic_Tumor.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Inflammatory_Myofibroblastic_Tumor.html#dataset-ega-egas00001005081"]},{"id":"dataset:ega:egas00001005094","accession":"ega:EGAS00001005094","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001005094","title":"Oncogenic mutations and gene fusions in CD30-positive lymphoproliferations and clonally related mycosis fungoides occurring in the same patients","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Mycosis Fungoides\"); description-level mentions were not accepted. EGA study_type: Cancer Genomics. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Mycosis_Fungoides","name":"Mycosis Fungoides","kind":"Disorder","source_path":"kb/disorders/Mycosis_Fungoides.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mycosis_Fungoides.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Mycosis_Fungoides.html#dataset-ega-egas00001005094"}],"context_names":["Mycosis Fungoides"],"disease_names":["Mycosis Fungoides"],"disease_name":"Mycosis Fungoides","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Mycosis_Fungoides.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mycosis_Fungoides.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Mycosis_Fungoides.html#dataset-ega-egas00001005094"]},{"id":"dataset:ega:egas00001005098","accession":"ega:EGAS00001005098","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001005098","title":"Hermansky-Pudlak syndrome type 1 causes impaired anti-microbial immunity  through a pathogenic lipid metabolism-mTOR circuit - 10x Genomics scRNAseq","alternate_titles":[],"description":"Mendelian diseases that present with immune-mediated disorders can provide insights into the molecular mechanisms that drive inflammation. Hermansky-Pudlak syndrome (HPS) types 1 and 4 are caused by defective vesicle trafficking involving the BLOC-3 complex. The presence of inflammatory complications such as Crohn’s disease-like inflammation and lung fibrosis in these patients remains enigmatic. Using mass cytometry we observe an augmented inflammatory monocyte compartment in HPS1 patient peripheral blood that may be associated with a TNF - and IL-1α-dominated cytokine dysregulation.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Hermansky-Pudlak Syndrome\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Hermansky_Pudlak_Syndrome","name":"Hermansky-Pudlak Syndrome","kind":"Disorder","source_path":"kb/disorders/Hermansky_Pudlak_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hermansky_Pudlak_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hermansky-Pudlak_Syndrome.html#dataset-ega-egas00001005098"}],"context_names":["Hermansky-Pudlak Syndrome"],"disease_names":["Hermansky-Pudlak Syndrome"],"disease_name":"Hermansky-Pudlak Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hermansky_Pudlak_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hermansky_Pudlak_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hermansky-Pudlak_Syndrome.html#dataset-ega-egas00001005098"]},{"id":"dataset:ega:egas00001005107","accession":"ega:EGAS00001005107","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001005107","title":"Chronic myelomonocytic leukemia","alternate_titles":[],"description":"Chronic myelomonocytic leukemia is an aggressive hematological malignancy with dismal outcomes, with the pCMML subtype in particular having median OS of <2 years and high rates of AML transformation (Patnaik et al., 2014). Given limited therapeutic options for affected patients, we carried out this study to define the genetic and epigenetic landscape of pCMML and identify therapies that could modify disease biology.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Chronic Myelomonocytic Leukemia\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Chronic_Myelomonocytic_Leukemia","name":"Chronic Myelomonocytic Leukemia","kind":"Disorder","source_path":"kb/disorders/Chronic_Myelomonocytic_Leukemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Myelomonocytic_Leukemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chronic_Myelomonocytic_Leukemia.html#dataset-ega-egas00001005107"}],"context_names":["Chronic Myelomonocytic Leukemia"],"disease_names":["Chronic Myelomonocytic Leukemia"],"disease_name":"Chronic Myelomonocytic Leukemia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chronic_Myelomonocytic_Leukemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Myelomonocytic_Leukemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chronic_Myelomonocytic_Leukemia.html#dataset-ega-egas00001005107"]},{"id":"dataset:ega:egas00001005117","accession":"ega:EGAS00001005117","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001005117","title":"Whole-exome sequencing performed on a patient with chronic myelomonocytic leukemia and B cell acute lymphoblastic leukemia","alternate_titles":[],"description":"We studied the rare case of a patient who underwent transformation of myelodysplastic syndrome to chronic myelomonocytic leukemia and B cell acute lymphoblastic leukemia. We used fluorescence-activated cell sorting and whole-exome sequencing to identify driver mutations in the various clones. This allowed us to propose a model of branching clonal evolution with a possible germline predisposition to cancer.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Chronic Myelomonocytic Leukemia\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Chronic_Myelomonocytic_Leukemia","name":"Chronic Myelomonocytic Leukemia","kind":"Disorder","source_path":"kb/disorders/Chronic_Myelomonocytic_Leukemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Myelomonocytic_Leukemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chronic_Myelomonocytic_Leukemia.html#dataset-ega-egas00001005117"}],"context_names":["Chronic Myelomonocytic Leukemia"],"disease_names":["Chronic Myelomonocytic Leukemia"],"disease_name":"Chronic Myelomonocytic Leukemia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chronic_Myelomonocytic_Leukemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Myelomonocytic_Leukemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chronic_Myelomonocytic_Leukemia.html#dataset-ega-egas00001005117"]},{"id":"dataset:ega:egas00001005182","accession":"ega:EGAS00001005182","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001005182","title":"Pediatric Papillary Thyroid Carcinoma RNA-Seq","alternate_titles":[],"description":"Papillary thyroid carcinoma (PTC) is the most common malignancy amongst adolescent and young adult women. Clinical and genomic features of PTC in children differ from those in adults. Historically, a substantial proportion (~50%) of pediatric PTC (PPTC) lack any of the common driver mutations typical of adult PTC. Thus, molecular diagnostics developed for adults may not be valid in children. We applied novel bioinformatic pipelines to RNASeq analysis of pediatric thyroid tumors to identify known and novel fusion oncogenes as drivers of tumorigenesis and to define gene expression patterns among tumors.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Papillary Thyroid Carcinoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Papillary_Thyroid_Carcinoma","name":"Papillary Thyroid Carcinoma","kind":"Disorder","source_path":"kb/disorders/Papillary_Thyroid_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Papillary_Thyroid_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Papillary_Thyroid_Carcinoma.html#dataset-ega-egas00001005182"}],"context_names":["Papillary Thyroid Carcinoma"],"disease_names":["Papillary Thyroid Carcinoma"],"disease_name":"Papillary Thyroid Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Papillary_Thyroid_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Papillary_Thyroid_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Papillary_Thyroid_Carcinoma.html#dataset-ega-egas00001005182"]},{"id":"dataset:ega:egas00001005214","accession":"ega:EGAS00001005214","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001005214","title":"Sclerosing epithelioid fibrosarcoma case report","alternate_titles":[],"description":"Sclerosing epithelioid fibrosarcoma (SEF) is a rare and aggressive soft tissue sarcomathought to originate in fibroblasts of the tissues surrounding tendons, ligaments and muscles. Minimally responsive to conventional cytotoxic chemotherapies, greater than 50% of SEF patients experience relapse and/or metastatic disease. SEF is most commonly discovered in middle-aged and elderly adults, but also rarely in children. A common gene fusion occurring between the EWSR1 and CREB3L1 genes has been observed in 80-90% of SEF cases. We describe here the youngest SEF patient reported to date (a 3-year-old Caucasian male) who presented with numerous bony and lung metastases.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Fibrosarcoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Fibrosarcoma","name":"Fibrosarcoma","kind":"Disorder","source_path":"kb/disorders/Fibrosarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fibrosarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Fibrosarcoma.html#dataset-ega-egas00001005214"}],"context_names":["Fibrosarcoma"],"disease_names":["Fibrosarcoma"],"disease_name":"Fibrosarcoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Fibrosarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fibrosarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Fibrosarcoma.html#dataset-ega-egas00001005214"]},{"id":"dataset:ega:egas00001005215","accession":"ega:EGAS00001005215","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001005215","title":"Sclerosing epithelioid fibrosarcoma case report","alternate_titles":[],"description":"Sclerosing epithelioid fibrosarcoma (SEF) is a rare and aggressive soft tissue sarcomathought to originate in fibroblasts of the tissues surrounding tendons, ligaments and muscles. Minimally responsive to conventional cytotoxic chemotherapies, greater than 50% of SEF patients experience relapse and/or metastatic disease. SEF is most commonly discovered in middle-aged and elderly adults, but also rarely in children. A common gene fusion occurring between the EWSR1 and CREB3L1 genes has been observed in 80-90% of SEF cases. We describe here the youngest SEF patient reported to date (a 3-year-old Caucasian male) who presented with numerous bony and lung metastases.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Fibrosarcoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Fibrosarcoma","name":"Fibrosarcoma","kind":"Disorder","source_path":"kb/disorders/Fibrosarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fibrosarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Fibrosarcoma.html#dataset-ega-egas00001005215"}],"context_names":["Fibrosarcoma"],"disease_names":["Fibrosarcoma"],"disease_name":"Fibrosarcoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Fibrosarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fibrosarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Fibrosarcoma.html#dataset-ega-egas00001005215"]},{"id":"dataset:ega:egas00001005351","accession":"ega:EGAS00001005351","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001005351","title":"Genomic characterization of co-existing biliary tract intraepithelial neoplasia and carcinoma lesions reveals distinct evolutionary paths of gallbladder cancer","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Gallbladder Cancer\"); description-level mentions were not accepted. EGA study_type: Cancer Genomics. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Gallbladder_Cancer","name":"Gallbladder Cancer","kind":"Disorder","source_path":"kb/disorders/Gallbladder_Cancer.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Gallbladder_Cancer.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Gallbladder_Cancer.html#dataset-ega-egas00001005351"}],"context_names":["Gallbladder Cancer"],"disease_names":["Gallbladder Cancer"],"disease_name":"Gallbladder Cancer","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Gallbladder_Cancer.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Gallbladder_Cancer.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Gallbladder_Cancer.html#dataset-ega-egas00001005351"]},{"id":"dataset:ega:egas00001005398","accession":"ega:EGAS00001005398","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001005398","title":"Prevalence of transthyretin amyloidosis in patients with heart failure and no left ventricular hypertrophy","alternate_titles":[],"description":"The study prospectively enrolled patients admitted for HF with LV ejection fraction (LVEF) ≥ 50% and LV wall thickness <12 mm. TTR cardiac amyloidosis was diagnosed according to accepted criteria, which include positive cardiac 99-Tc-DPD scintigraphy in the absence of monoclonal protein expansion in blood. In a cohort of patients with HFpEF without LVH, the prevalence of TTR cardiac amyloidosis was 5%. Transthyretin gene sequencing was performed in positive patients.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Heart Failure\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Heart_Failure","name":"Heart Failure","kind":"Disorder","source_path":"kb/disorders/Heart_Failure.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Heart_Failure.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Heart_Failure.html#dataset-ega-egas00001005398"}],"context_names":["Heart Failure"],"disease_names":["Heart Failure"],"disease_name":"Heart Failure","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Heart_Failure.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Heart_Failure.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Heart_Failure.html#dataset-ega-egas00001005398"]},{"id":"dataset:ega:egas00001005435","accession":"ega:EGAS00001005435","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001005435","title":"Risk alleles of membranous nephropathy and recurrence of the disease on the grafted kidney","alternate_titles":[],"description":"The goal of the project was to identify risk alleles that are associated with recurrence of membranous nephropathy in the graft after kidney transplantation. First, we sequenced PLA2R1 and HLA-D loci in 248 patients with primary membranous nephropathy and identified two independent single nucleotide polymorphisms (SNPs) at risk for primary membranous nephropathy at each locus. Then we investigated whether primary membranous nephropathy at-risk variants were associated with recurrence in a retrospective cohort of 105 donor-recipient pairs and a replication cohort of 40 pairs.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Membranous nephropathy\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Membranous_Nephropathy","name":"Membranous nephropathy","kind":"Disorder","source_path":"kb/disorders/Membranous_Nephropathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Membranous_Nephropathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Membranous_nephropathy.html#dataset-ega-egas00001005435"}],"context_names":["Membranous nephropathy"],"disease_names":["Membranous nephropathy"],"disease_name":"Membranous nephropathy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Membranous_Nephropathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Membranous_Nephropathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Membranous_nephropathy.html#dataset-ega-egas00001005435"]},{"id":"dataset:ega:egas00001005463","accession":"ega:EGAS00001005463","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001005463","title":"Bruno et al.: Interferon gamma rebalances immunopathological signatures in Chronic Granulomatous Disease through metabolic rewiring","alternate_titles":[],"description":"Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by recurrent life-threatening infections and hyperinflammatory complications. It is caused by mutations in the NADPH oxidase complex and the consequent loss of reactive oxygen species (ROS) production. Recombinant human interferon gamma (rIFN-γ) prophylaxis reduces the risk of severe infections, but the mechanisms behind its efficacy in CGD are still an open question, as it does not restore NADPH oxidase-dependent ROS production.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Chronic Granulomatous Disease\"); description-level mentions were not accepted. EGA study_type: Transcriptome Analysis. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Chronic_Granulomatous_Disease","name":"Chronic Granulomatous Disease","kind":"Disorder","source_path":"kb/disorders/Chronic_Granulomatous_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Granulomatous_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chronic_Granulomatous_Disease.html#dataset-ega-egas00001005463"}],"context_names":["Chronic Granulomatous Disease"],"disease_names":["Chronic Granulomatous Disease"],"disease_name":"Chronic Granulomatous Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chronic_Granulomatous_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Granulomatous_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chronic_Granulomatous_Disease.html#dataset-ega-egas00001005463"]},{"id":"dataset:ega:egas00001005502","accession":"ega:EGAS00001005502","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001005502","title":"Embryonal Rhabdomyosarcoma sequencing data","alternate_titles":[],"description":"This study shares DNA and RNA sequencing data from embryonal rhadbomyosarcoma patients","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Embryonal Rhabdomyosarcoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Embryonal_Rhabdomyosarcoma","name":"Embryonal Rhabdomyosarcoma","kind":"Disorder","source_path":"kb/disorders/Embryonal_Rhabdomyosarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Embryonal_Rhabdomyosarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Embryonal_Rhabdomyosarcoma.html#dataset-ega-egas00001005502"}],"context_names":["Embryonal Rhabdomyosarcoma"],"disease_names":["Embryonal Rhabdomyosarcoma"],"disease_name":"Embryonal Rhabdomyosarcoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Embryonal_Rhabdomyosarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Embryonal_Rhabdomyosarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Embryonal_Rhabdomyosarcoma.html#dataset-ega-egas00001005502"]},{"id":"dataset:ega:egas00001005530","accession":"ega:EGAS00001005530","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001005530","title":"Pathogenic Neurofibromatosis type 1 (NF1) RNA splicing resolved by targeted RNAseq","alternate_titles":[],"description":"Neurofibromatosis type 1 (NF1) is caused by loss-of-function variants in the NF1 gene. Approximately 10% of these variants affect RNA splicing and are either missed by conventional DNA diagnostics or are misinterpreted by in silico splicing predictions. Therefore, a targeted RNAseq-based approach was designed to detect pathogenic RNA splicing and associated pathogenic DNA variants. an in-house developed tool (QURNAS) was used to calculate the enrichment score (ERS) for each splicing event. RNA enrichment of NF1 and SPRED1 was done using SPET (NUGEN - NF1 only) and using SureSelect (Agilent - NF1 and SPRED1).","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:34782607"],"publication_contexts":[{"context_id":"disorder:Neurofibromatosis_Type_1","publication":"PMID:34782607"}],"publication":"PMID:34782607","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34782607","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Neurofibromatosis Type 1\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Neurofibromatosis_Type_1","name":"Neurofibromatosis Type 1","kind":"Disorder","source_path":"kb/disorders/Neurofibromatosis_Type_1.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Neurofibromatosis_Type_1.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Neurofibromatosis_Type_1.html#dataset-ega-egas00001005530"}],"context_names":["Neurofibromatosis Type 1"],"disease_names":["Neurofibromatosis Type 1"],"disease_name":"Neurofibromatosis Type 1","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Neurofibromatosis_Type_1.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Neurofibromatosis_Type_1.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Neurofibromatosis_Type_1.html#dataset-ega-egas00001005530"]},{"id":"dataset:ega:egas00001005588","accession":"ega:EGAS00001005588","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001005588","title":"RNA-sequencing of tumors from 45 patients with recurrent or metastatic gastric cancer treated with immune checkpoint inhibitors","alternate_titles":[],"description":"Genomic profiling can provide prognostic and predictive information to guide clinical care. Biomarkers that reliably predict patient response to chemotherapy and immune checkpoint inhibition in gastric cancer are lacking. In this work, we used our machine learning algorithm NTriPath to identify a gastric-cancer specific 32-gene signature. Using unsupervised clustering on expression levels of these 32 genes in tumors from 567 patients, we identified four molecular subtypes that were prognostic for survival.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Metastatic Gastric Cancer\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Gastric_Adenocarcinoma","name":"Gastric Adenocarcinoma","kind":"Disorder","source_path":"kb/disorders/Gastric_Adenocarcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Gastric_Adenocarcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Gastric_Adenocarcinoma.html#dataset-ega-egas00001005588"}],"context_names":["Gastric Adenocarcinoma"],"disease_names":["Gastric Adenocarcinoma"],"disease_name":"Gastric Adenocarcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Gastric_Adenocarcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Gastric_Adenocarcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Gastric_Adenocarcinoma.html#dataset-ega-egas00001005588"]},{"id":"dataset:ega:egas00001005665","accession":"ega:EGAS00001005665","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001005665","title":"DGCR8 and the six hit, three-step model of schwannomatosis","alternate_titles":[],"description":"In our manuscript, we report the second case of a patient with peripheral schwannomatosis and thyroid alterations cause by the germline pathogenic variant E518K in DGCR8 and analyzed a total of 13 schwannomas from patients in the two kindreds identified up to date. Our analyses revealed how path to tumorigenesis prompted by DGCR8 requires the loss of the wild type allele of Chrm22q and in more than two thirds of the tumors a complete inactivation of NF2.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Schwannomatosis\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Schwannomatosis","name":"Schwannomatosis","kind":"Disorder","source_path":"kb/disorders/Schwannomatosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Schwannomatosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Schwannomatosis.html#dataset-ega-egas00001005665"}],"context_names":["Schwannomatosis"],"disease_names":["Schwannomatosis"],"disease_name":"Schwannomatosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Schwannomatosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Schwannomatosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Schwannomatosis.html#dataset-ega-egas00001005665"]},{"id":"dataset:ega:egas00001005744","accession":"ega:EGAS00001005744","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001005744","title":"IN UTERO ORIGIN OF MYELOFIBROSIS PRESENTING IN ADULT MONOZYGOTIC TWINS AFTER A PROLONGED DISEASE LATENCY","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Myelofibrosis\"); description-level mentions were not accepted. EGA study_type: Cancer Genomics. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Primary_Myelofibrosis","name":"Primary Myelofibrosis","kind":"Disorder","source_path":"kb/disorders/Primary_Myelofibrosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Primary_Myelofibrosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Myelofibrosis.html#dataset-ega-egas00001005744"}],"context_names":["Primary Myelofibrosis"],"disease_names":["Primary Myelofibrosis"],"disease_name":"Primary Myelofibrosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Primary_Myelofibrosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Primary_Myelofibrosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Primary_Myelofibrosis.html#dataset-ega-egas00001005744"]},{"id":"dataset:ega:egas00001005794","accession":"ega:EGAS00001005794","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001005794","title":"Profibrotic priming of airway cell types in idiopathic pulmonary fibrosis and drug inhibition in single-cell resolution","alternate_titles":[],"description":"The cause and etiology of idiopathic pulmonary fibrosis, a severe chronic lung disorder with limited treatment options, is still poorly understood. Early genetic studies hinted that airway epithelial cells play an important role in the development of IPF while more recent single-cell RNA sequencing atlases from explant IPF lungs have focused on macrophages. In this study, we used air-liquid interface cultures of primary cells taken from the subsegmental bronchi of IPF patients, reflecting early-stage fibrosis, to interrogate the single-cell transcriptional landscape of the airway mucosa. We identified IPF-enriched cell-cell interaction pathways.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Idiopathic Pulmonary Fibrosis\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Idiopathic_Pulmonary_Fibrosis","name":"Idiopathic Pulmonary Fibrosis","kind":"Disorder","source_path":"kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Idiopathic_Pulmonary_Fibrosis.html#dataset-ega-egas00001005794"}],"context_names":["Idiopathic Pulmonary Fibrosis"],"disease_names":["Idiopathic Pulmonary Fibrosis"],"disease_name":"Idiopathic Pulmonary Fibrosis","same_context_model_ids":["model:kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml:Immune-cell-free AT2-lineage and fibroblast organoids","model:kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml:Microengineered alveolar array lung-on-chip with breathing mechanics"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Idiopathic_Pulmonary_Fibrosis.html#dataset-ega-egas00001005794"]},{"id":"dataset:ega:egas00001005830","accession":"ega:EGAS00001005830","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001005830","title":"Full blood mRNA sequencing of myotonic dystrophy type 1 patients after cognitive behavioural therapy","alternate_titles":[],"description":"Myotonic dystrophy type 1 (DM1) is an incurable multisystem disease caused by a CTG-repeat expansion in the DM1 protein kinase (DMPK) gene. The OPTIMISTIC clinical trial demonstrated positive and heterogenous effects of cognitive behavioral therapy (CBT) on the capacity for activity and social participations in DM1 patients. Here, we performed mRNA sequencing of full blood for 27 patients of the OPTIMISTIC cohort before and after the CBT intervention. We identified 608 genes for which their expression was significantly associated with the disease causing CTG-repeat expansion, as well as with 1176 genes significantly associated with the average clinical response towards the intervention.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:29934199"],"publication_contexts":[{"context_id":"disorder:Myotonic_Dystrophy_Type_1","publication":"PMID:29934199"}],"publication":"PMID:29934199","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/29934199","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Myotonic Dystrophy Type 1\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Myotonic_Dystrophy_Type_1","name":"Myotonic Dystrophy Type 1","kind":"Disorder","source_path":"kb/disorders/Myotonic_Dystrophy_Type_1.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myotonic_Dystrophy_Type_1.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Myotonic_Dystrophy_Type_1.html#dataset-ega-egas00001005830"}],"context_names":["Myotonic Dystrophy Type 1"],"disease_names":["Myotonic Dystrophy Type 1"],"disease_name":"Myotonic Dystrophy Type 1","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Myotonic_Dystrophy_Type_1.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myotonic_Dystrophy_Type_1.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Myotonic_Dystrophy_Type_1.html#dataset-ega-egas00001005830"]},{"id":"dataset:ega:egas00001005848","accession":"ega:EGAS00001005848","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001005848","title":"Searching for genetic modulators of the phenotypic heterogeneity in Brugada Syndrome","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["WES"],"data_type_labels":["Whole exome sequencing"],"data_type_label":"Whole exome sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Brugada syndrome\"); description-level mentions were not accepted. EGA study_type: Exome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Brugada_Syndrome","name":"Brugada syndrome","kind":"Disorder","source_path":"kb/disorders/Brugada_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Brugada_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Brugada_syndrome.html#dataset-ega-egas00001005848"}],"context_names":["Brugada syndrome"],"disease_names":["Brugada syndrome"],"disease_name":"Brugada syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Brugada_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Brugada_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Brugada_syndrome.html#dataset-ega-egas00001005848"]},{"id":"dataset:ega:egas00001005861","accession":"ega:EGAS00001005861","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001005861","title":"Single-nuclei gene-expression analysis of pheochromocytoma and paraganglioma links tumor subtypes with tumor microenvironment","alternate_titles":[],"description":"Pheochromocytomas and paragangliomas (PCPG) are rare neuroendocrine tumors associated with autonomic nerves. We used single nuclei-RNA-seq (snRNA-seq) for analysis of 30 PCPG representing 13 known driver genes, plus two normal adrenal medullas to dissect cell composition, refine PCPG subtypes and compare PCPG and normal tissue expression. Incorporating bulk-tissue and snRNA-seq data we identified seven PCPG gene-expression subtypes with genotype and cell type associations.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Pheochromocytoma and Paraganglioma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Pheochromocytoma_Paraganglioma","name":"Pheochromocytoma and Paraganglioma","kind":"Disorder","source_path":"kb/disorders/Pheochromocytoma_Paraganglioma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pheochromocytoma_Paraganglioma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pheochromocytoma_and_Paraganglioma.html#dataset-ega-egas00001005861"}],"context_names":["Pheochromocytoma and Paraganglioma"],"disease_names":["Pheochromocytoma and Paraganglioma"],"disease_name":"Pheochromocytoma and Paraganglioma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Pheochromocytoma_Paraganglioma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pheochromocytoma_Paraganglioma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Pheochromocytoma_and_Paraganglioma.html#dataset-ega-egas00001005861"]},{"id":"dataset:ega:egas00001005889","accession":"ega:EGAS00001005889","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001005889","title":"Single cell analysis of cultivated fibroblasts from chronic pancreatitis and pancreatic cancer patients","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Chronic Pancreatitis\"); description-level mentions were not accepted. EGA study_type: RNASeq. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Chronic_Pancreatitis","name":"Chronic Pancreatitis","kind":"Disorder","source_path":"kb/disorders/Chronic_Pancreatitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Pancreatitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chronic_Pancreatitis.html#dataset-ega-egas00001005889"}],"context_names":["Chronic Pancreatitis"],"disease_names":["Chronic Pancreatitis"],"disease_name":"Chronic Pancreatitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chronic_Pancreatitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Pancreatitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chronic_Pancreatitis.html#dataset-ega-egas00001005889"]},{"id":"dataset:ega:egas00001005892","accession":"ega:EGAS00001005892","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001005892","title":"Functional Mapping of AKT Signaling and Biomarkers of Response From the FAIRLANE Trial of Neoadjuvant Ipatasertib Plus Paclitaxel for Triple-Negative Breast Cancer","alternate_titles":[],"description":"Purpose: Despite extensive genomic and transcriptomic profiling, it remains unknown how signaling pathways are differentially activated and how tumors are differentially sensitized to certain perturbations. Here, we aim to characterize AKT signaling activity and its association with other genomic or immunohistochemistry-based PI3K/AKT pathway biomarkers as well as the clinical activity of ipatasertib (AKT inhibitor) in the FAIRLANE trial. Experimental Design: In FAIRLANE, 151 patients with early triple-negative breast cancer were randomized 1:1 to receive paclitaxel with ipatasertib or placebo for 12 weeks prior to surgery.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Triple-Negative Breast Cancer\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Triple_Negative_Breast_Cancer","name":"Triple-Negative Breast Cancer","kind":"Disorder","source_path":"kb/disorders/Triple_Negative_Breast_Cancer.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Triple_Negative_Breast_Cancer.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Triple-Negative_Breast_Cancer.html#dataset-ega-egas00001005892"}],"context_names":["Triple-Negative Breast Cancer"],"disease_names":["Triple-Negative Breast Cancer"],"disease_name":"Triple-Negative Breast Cancer","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Triple_Negative_Breast_Cancer.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Triple_Negative_Breast_Cancer.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Triple-Negative_Breast_Cancer.html#dataset-ega-egas00001005892"]},{"id":"dataset:ega:egas00001005983","accession":"ega:EGAS00001005983","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001005983","title":"Epithelioid sarcoma sequencing data","alternate_titles":[],"description":"This study shares DNA and RNA sequencing data from Epithelioid sarcoma patients","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Epithelioid Sarcoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Epithelioid_Sarcoma","name":"Epithelioid Sarcoma","kind":"Disorder","source_path":"kb/disorders/Epithelioid_Sarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Epithelioid_Sarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Epithelioid_Sarcoma.html#dataset-ega-egas00001005983"}],"context_names":["Epithelioid Sarcoma"],"disease_names":["Epithelioid Sarcoma"],"disease_name":"Epithelioid Sarcoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Epithelioid_Sarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Epithelioid_Sarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Epithelioid_Sarcoma.html#dataset-ega-egas00001005983"]},{"id":"dataset:ega:egas00001005993","accession":"ega:EGAS00001005993","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001005993","title":"Host genotyping data from Dutch adult bacterial meningitis patients and linked bacterial genome sequences","alternate_titles":[],"description":"Streptococcus pneumoniae is a common nasopharyngeal colonizer, but can also cause life-threatening invasive diseases such as empyema, bacteremia and meningitis. Genetic variation of host and pathogen is known to play a role in invasive pneumococcal disease, though to what extent is unknown. This study includes 1146 samples of host genotyping data (genotyped and imputed) from Illumina Omni arrays. Samples were collected from adults (>16 yrs) patients with CSF confirmed bacterial meningitis in the Netherlands between 2006 and 2015. Metadata includes patient outcome, species of bacteria, and for 467 samples a link to an ENA run with the associated bacterial genome (S. pneumoniae only).","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:31092817"],"publication_contexts":[{"context_id":"disorder:Bacterial_meningitis","publication":"PMID:31092817"}],"publication":"PMID:31092817","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/31092817","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Bacterial meningitis\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Bacterial_meningitis","name":"Bacterial meningitis","kind":"Disorder","source_path":"kb/disorders/Bacterial_meningitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bacterial_meningitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Bacterial_meningitis.html#dataset-ega-egas00001005993"}],"context_names":["Bacterial meningitis"],"disease_names":["Bacterial meningitis"],"disease_name":"Bacterial meningitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Bacterial_meningitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bacterial_meningitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Bacterial_meningitis.html#dataset-ega-egas00001005993"]},{"id":"dataset:ega:egas00001006037","accession":"ega:EGAS00001006037","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001006037","title":"The KATHERINE study of adjuvant trastuzumab emtansine in HER2-positive breast cancer: analysis of patients with HER2-negative residual invasive disease on re-testing","alternate_titles":[],"description":"Following chemotherapy and human epidermal growth factor 2 (HER2)-targeted neoadjuvant therapy for HER2-positive early breast cancer, residual invasive breast cancer at surgery may be HER2-negative on retesting in some patients. We evaluated outcomes with T-DM1 and trastuzumab in patients randomized in the phase III KATHERINE trial based on HER2-positive central testing of the core biopsy with HER2-negative central testing on their corresponding surgical specimen.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"HER2-Positive Breast Cancer\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:HER2_Positive_Breast_Cancer","name":"HER2-Positive Breast Cancer","kind":"Disorder","source_path":"kb/disorders/HER2_Positive_Breast_Cancer.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/HER2_Positive_Breast_Cancer.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/HER2-Positive_Breast_Cancer.html#dataset-ega-egas00001006037"}],"context_names":["HER2-Positive Breast Cancer"],"disease_names":["HER2-Positive Breast Cancer"],"disease_name":"HER2-Positive Breast Cancer","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/HER2_Positive_Breast_Cancer.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/HER2_Positive_Breast_Cancer.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/HER2-Positive_Breast_Cancer.html#dataset-ega-egas00001006037"]},{"id":"dataset:ega:egas00001006069","accession":"ega:EGAS00001006069","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001006069","title":"Genomic landscape of malignant peripheral nerve sheath tumor (MPNST)","alternate_titles":[],"description":"Neurofibromatosis type 1 (NF1) is the most common tumor predisposition syndrome, and is associated with an aggressive soft-tissue sarcoma, malignant peripheral nerve sheath tumours (MPNSTs), the greatest cause of morbidity and mortality in people with NF1. 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The development of novel therapies has been largely hindered by a lack of understanding of the molecular events underpinning MPNST pathogenesis.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Malignant Peripheral Nerve Sheath Tumor\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Malignant_Peripheral_Nerve_Sheath_Tumor","name":"Malignant Peripheral Nerve Sheath Tumor","kind":"Disorder","source_path":"kb/disorders/Malignant_Peripheral_Nerve_Sheath_Tumor.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Malignant_Peripheral_Nerve_Sheath_Tumor.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Malignant_Peripheral_Nerve_Sheath_Tumor.html#dataset-ega-egas00001006069"}],"context_names":["Malignant Peripheral Nerve Sheath Tumor"],"disease_names":["Malignant Peripheral Nerve Sheath Tumor"],"disease_name":"Malignant Peripheral Nerve Sheath Tumor","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Malignant_Peripheral_Nerve_Sheath_Tumor.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Malignant_Peripheral_Nerve_Sheath_Tumor.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Malignant_Peripheral_Nerve_Sheath_Tumor.html#dataset-ega-egas00001006069"]},{"id":"dataset:ega:egas00001006072","accession":"ega:EGAS00001006072","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001006072","title":"Clear cell sarcoma sequencing data","alternate_titles":[],"description":"This study shares DNA and RNA sequencing data from Clear cell sarcoma patients","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Clear Cell Sarcoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Clear_Cell_Sarcoma","name":"Clear Cell Sarcoma","kind":"Disorder","source_path":"kb/disorders/Clear_Cell_Sarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Clear_Cell_Sarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Clear_Cell_Sarcoma.html#dataset-ega-egas00001006072"}],"context_names":["Clear Cell Sarcoma"],"disease_names":["Clear Cell Sarcoma"],"disease_name":"Clear Cell Sarcoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Clear_Cell_Sarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Clear_Cell_Sarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Clear_Cell_Sarcoma.html#dataset-ega-egas00001006072"]},{"id":"dataset:ega:egas00001006079","accession":"ega:EGAS00001006079","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001006079","title":"Comprehensive Molecular Profiling Identifies Features of Disease Resistance to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Triple-Negative Breast Cancer\"); description-level mentions were not accepted. EGA study_type: Cancer Genomics. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Triple_Negative_Breast_Cancer","name":"Triple-Negative Breast Cancer","kind":"Disorder","source_path":"kb/disorders/Triple_Negative_Breast_Cancer.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Triple_Negative_Breast_Cancer.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Triple-Negative_Breast_Cancer.html#dataset-ega-egas00001006079"}],"context_names":["Triple-Negative Breast Cancer"],"disease_names":["Triple-Negative Breast Cancer"],"disease_name":"Triple-Negative Breast Cancer","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Triple_Negative_Breast_Cancer.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Triple_Negative_Breast_Cancer.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Triple-Negative_Breast_Cancer.html#dataset-ega-egas00001006079"]},{"id":"dataset:ega:egas00001006133","accession":"ega:EGAS00001006133","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001006133","title":"Discriminating Th17.1 cell driven sarcoidosis-like inflammation from relapse after anti-BCMA CAR T cells in multiple myeloma","alternate_titles":[],"description":"We present a case study on sarcoidosis-like flare-up after Idecabtagen Vicleucel (Ide-cel), a BCMA targeting CAR T cell therapy, and identified a Th17.1 driven autoimmune mechanism as the biological underpinning of this phenomenon using single-cell RNA-seq analysis. Furthermore, single-cell RNA-seq allowed to discriminate between immune-mediated changes and true relapse after CAR T cell treatment.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Sarcoidosis\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Sarcoidosis","name":"Sarcoidosis","kind":"Disorder","source_path":"kb/disorders/Sarcoidosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sarcoidosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Sarcoidosis.html#dataset-ega-egas00001006133"}],"context_names":["Sarcoidosis"],"disease_names":["Sarcoidosis"],"disease_name":"Sarcoidosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Sarcoidosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sarcoidosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Sarcoidosis.html#dataset-ega-egas00001006133"]},{"id":"dataset:ega:egas00001006229","accession":"ega:EGAS00001006229","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001006229","title":"Biomarker Data from KATHERINE: A Phase III Study of Adjuvant Trastuzumab Emtansine versus Trastuzumab in Patients with Residual Invasive Disease after Neoadjuvant Therapy for HER2-Positive Breast Cancer","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"HER2-Positive Breast Cancer\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:HER2_Positive_Breast_Cancer","name":"HER2-Positive Breast Cancer","kind":"Disorder","source_path":"kb/disorders/HER2_Positive_Breast_Cancer.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/HER2_Positive_Breast_Cancer.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/HER2-Positive_Breast_Cancer.html#dataset-ega-egas00001006229"}],"context_names":["HER2-Positive Breast Cancer"],"disease_names":["HER2-Positive Breast Cancer"],"disease_name":"HER2-Positive Breast Cancer","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/HER2_Positive_Breast_Cancer.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/HER2_Positive_Breast_Cancer.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/HER2-Positive_Breast_Cancer.html#dataset-ega-egas00001006229"]},{"id":"dataset:ega:egas00001006242","accession":"ega:EGAS00001006242","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001006242","title":"RNA-sequencing of mechanical stress induced osteoarthritis-like damage in aged human cartilage explants treated with the anti-deiodinase iopanoic acid","alternate_titles":[],"description":"The current study aimed to confirm chondroprotective effects of the D2 inhibitor iopanoic acid (IOP) in an ex vivo aged human osteochondral explant model in which injurious mechanical stress is applied to inflict OA-like damage. 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Differential expression analysis and weighted gene co-expression network analysis were performed to identify gene expression signatures, while deconvolution and flow cytometry to characterize the peripheral blood immune cell profile.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Psoriatic Arthritis\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Psoriatic_Arthritis","name":"Psoriatic Arthritis","kind":"Disorder","source_path":"kb/disorders/Psoriatic_Arthritis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Psoriatic_Arthritis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Psoriatic_Arthritis.html#dataset-ega-egas00001006288"}],"context_names":["Psoriatic Arthritis"],"disease_names":["Psoriatic Arthritis"],"disease_name":"Psoriatic Arthritis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Psoriatic_Arthritis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Psoriatic_Arthritis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Psoriatic_Arthritis.html#dataset-ega-egas00001006288"]},{"id":"dataset:ega:egas00001006330","accession":"ega:EGAS00001006330","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001006330","title":"Spatial multi-omic map of human myocardial infarction","alternate_titles":[],"description":"Myocardial infarction is a leading cause of mortality worldwide 1 . While advances have been made in acute treatment, an incomplete understanding of remodelling processes has limited the effectiveness of therapies to reduce late-stage mortality 2 . Here, we generate an integrative high- resolution map of human cardiac remodelling after myocardial infarction using single-cell gene expression, chromatin accessibility, and spatial transcriptomic profiling of multiple physiological zones at distinct time points in myocardium from myocardial infarction and control patients.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Myocardial Infarction\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Myocardial_Infarction","name":"Myocardial Infarction","kind":"Disorder","source_path":"kb/disorders/Myocardial_Infarction.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myocardial_Infarction.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Myocardial_Infarction.html#dataset-ega-egas00001006330"}],"context_names":["Myocardial Infarction"],"disease_names":["Myocardial Infarction"],"disease_name":"Myocardial Infarction","same_context_model_ids":["model:kb/disorders/Myocardial_Infarction.yaml:Bioelectronically instrumented heart-on-a-chip under acute hypoxia","model:kb/disorders/Myocardial_Infarction.yaml:Epicardial-myocardial heart-on-a-chip model of ischemia-reperfusion injury","model:kb/disorders/Myocardial_Infarction.yaml:Human cardiac infarct organoid with an internal oxygen-diffusion gradient","model:kb/disorders/Myocardial_Infarction.yaml:Human heart-on-a-chip ischemia-reperfusion assay with endothelial extracellular vesicle rescue","model:kb/disorders/Myocardial_Infarction.yaml:Myocardial infarct border-zone-on-a-chip"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Myocardial_Infarction.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myocardial_Infarction.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Myocardial_Infarction.html#dataset-ega-egas00001006330"]},{"id":"dataset:ega:egas00001006351","accession":"ega:EGAS00001006351","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001006351","title":"Rhabdoid tumor sequencing data","alternate_titles":[],"description":"This study contains sequencing DNA and RNA sequencing data for rhabdoid tumors","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Rhabdoid Tumor\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Rhabdoid_Tumor","name":"Rhabdoid Tumor","kind":"Disorder","source_path":"kb/disorders/Rhabdoid_Tumor.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rhabdoid_Tumor.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Rhabdoid_Tumor.html#dataset-ega-egas00001006351"}],"context_names":["Rhabdoid Tumor"],"disease_names":["Rhabdoid Tumor"],"disease_name":"Rhabdoid Tumor","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Rhabdoid_Tumor.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rhabdoid_Tumor.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Rhabdoid_Tumor.html#dataset-ega-egas00001006351"]},{"id":"dataset:ega:egas00001006368","accession":"ega:EGAS00001006368","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001006368","title":"Allelic overload and its clinical modifier effect in Bardet-Biedl syndrome","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["WES"],"data_type_labels":["Whole exome sequencing"],"data_type_label":"Whole exome sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Bardet-Biedl syndrome\"); description-level mentions were not accepted. EGA study_type: Exome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Bardet-Biedl_Syndrome","name":"Bardet-Biedl syndrome","kind":"Disorder","source_path":"kb/disorders/Bardet-Biedl_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bardet-Biedl_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Bardet-Biedl_syndrome.html#dataset-ega-egas00001006368"}],"context_names":["Bardet-Biedl syndrome"],"disease_names":["Bardet-Biedl syndrome"],"disease_name":"Bardet-Biedl syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Bardet-Biedl_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bardet-Biedl_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Bardet-Biedl_syndrome.html#dataset-ega-egas00001006368"]},{"id":"dataset:ega:egas00001006388","accession":"ega:EGAS00001006388","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001006388","title":"Detection and genomic analysis of BRAF fusions in Juvenile Pilocytic Astrocytoma through the combination and integration of multi-omic data","alternate_titles":[],"description":"Juvenile Pilocytic Astrocytoma (JPAs) are highly vascular tumors and show pervasive immune infiltration, which can lead to low tumor cell purity in clinical samples. In some instances, this results in gene fusions that are difficult to detect with conventional omics approaches including RNA-Seq. To this effect, we applied RNA-Seq as well as linked-read whole-genome sequencing and in situ Hi-C as new approaches to detect and characterize low-frequency gene fusions at the genomic, transcriptomic and spatial level. Overall, we demonstrate the power of integrating multi-omic datasets to identify low frequency fusions and characterize the JPA genome at high resolution.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Pilocytic Astrocytoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Pilocytic_Astrocytoma","name":"Pilocytic Astrocytoma","kind":"Disorder","source_path":"kb/disorders/Pilocytic_Astrocytoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pilocytic_Astrocytoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pilocytic_Astrocytoma.html#dataset-ega-egas00001006388"}],"context_names":["Pilocytic Astrocytoma"],"disease_names":["Pilocytic Astrocytoma"],"disease_name":"Pilocytic Astrocytoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Pilocytic_Astrocytoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pilocytic_Astrocytoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Pilocytic_Astrocytoma.html#dataset-ega-egas00001006388"]},{"id":"dataset:ega:egas00001006389","accession":"ega:EGAS00001006389","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001006389","title":"Unraveling the genetics of transformed splenic marginal zone lymphoma","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Splenic Marginal Zone Lymphoma\"); description-level mentions were not accepted. EGA study_type: Cancer Genomics. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Splenic_Marginal_Zone_Lymphoma","name":"Splenic Marginal Zone Lymphoma","kind":"Disorder","source_path":"kb/disorders/Splenic_Marginal_Zone_Lymphoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Splenic_Marginal_Zone_Lymphoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Splenic_Marginal_Zone_Lymphoma.html#dataset-ega-egas00001006389"}],"context_names":["Splenic Marginal Zone Lymphoma"],"disease_names":["Splenic Marginal Zone Lymphoma"],"disease_name":"Splenic Marginal Zone Lymphoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Splenic_Marginal_Zone_Lymphoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Splenic_Marginal_Zone_Lymphoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Splenic_Marginal_Zone_Lymphoma.html#dataset-ega-egas00001006389"]},{"id":"dataset:ega:egas00001006398","accession":"ega:EGAS00001006398","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001006398","title":"Multi-omics analyses of airway host-microbe interactions in chronic obstructive pulmonary disease identify potential therapeutic interventions","alternate_titles":[],"description":"The mechanistic role of the airway microbiome in chronic obstructive pulmonary disease (COPD) remains largely unexplored. We present a landscape of airway microbe-host interactions in COPD through an in-depth profiling of the sputum metagenome, metabolome, host transcriptome and proteome from 99 COPD patients and 36 healthy individuals in China.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Chronic Obstructive Pulmonary Disease\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Chronic_Obstructive_Pulmonary_Disease","name":"Chronic_Obstructive_Pulmonary_Disease","kind":"Disorder","source_path":"kb/disorders/Chronic_Obstructive_Pulmonary_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Obstructive_Pulmonary_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chronic_Obstructive_Pulmonary_Disease.html#dataset-ega-egas00001006398"}],"context_names":["Chronic_Obstructive_Pulmonary_Disease"],"disease_names":["Chronic_Obstructive_Pulmonary_Disease"],"disease_name":"Chronic_Obstructive_Pulmonary_Disease","same_context_model_ids":["model:kb/disorders/Chronic_Obstructive_Pulmonary_Disease.yaml:Open-top vascularized alveolus-on-chip whole cigarette smoke model","model:kb/disorders/Chronic_Obstructive_Pulmonary_Disease.yaml:Patient-derived epithelial-endothelial COPD airway-on-a-chip"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Chronic_Obstructive_Pulmonary_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Obstructive_Pulmonary_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chronic_Obstructive_Pulmonary_Disease.html#dataset-ega-egas00001006398"]},{"id":"dataset:ega:egas00001006402","accession":"ega:EGAS00001006402","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001006402","title":"Proteogenomics reveals two distinct biological pilocytic astrocytoma subgroups","alternate_titles":[],"description":"Pilocytic astrocytoma (PA) is the most common pediatric brain tumor and driven by aberrant MAPK signaling, typically mediated by BRAF alterations. While five-year overall survival rates exceed 95%, tumor recurrence constitutes a major clinical challenge in incompletely resected tumors despite chemotherapeutic or radiation based therapies. Therefore, we used proteogenomics to discern the biological heterogeneity of PA to improve classification of this tumor entity and identify novel therapeutic targets. Our proteogenomics approach integrates RNA sequencing and LC/MS-based proteomic profiling data from a cohort of 58 confirmed, primary PA samples.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Pilocytic Astrocytoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Pilocytic_Astrocytoma","name":"Pilocytic Astrocytoma","kind":"Disorder","source_path":"kb/disorders/Pilocytic_Astrocytoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pilocytic_Astrocytoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pilocytic_Astrocytoma.html#dataset-ega-egas00001006402"}],"context_names":["Pilocytic Astrocytoma"],"disease_names":["Pilocytic Astrocytoma"],"disease_name":"Pilocytic Astrocytoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Pilocytic_Astrocytoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pilocytic_Astrocytoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Pilocytic_Astrocytoma.html#dataset-ega-egas00001006402"]},{"id":"dataset:ega:egas00001006406","accession":"ega:EGAS00001006406","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001006406","title":"DNA methylation-based prognostic subtypes of chordoma tumors in tissue","alternate_titles":[],"description":"Chordomas are rare malignant bone cancers of the skull-base and spine. Patient survival is variable and not reliably predicted using clinical factors or molecular features. This study identifies prognostic epigenetic chordoma subtypes that are detected noninvasively using plasma methylomes. Methylation profiles of 68 chordoma surgical samples were obtained between 1996 and 2018 across three international centers along with matched plasma methylomes where available. Consensus clustering identified two stable tissue clusters with a disease-specific survival difference that was independent of clinical factors in a multivariate Cox analysis (HR = 14.2, 95%CI: 2.1–94.8, P = 0.0063).","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Chordoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Chordoma","name":"Chordoma","kind":"Disorder","source_path":"kb/disorders/Chordoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chordoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chordoma.html#dataset-ega-egas00001006406"}],"context_names":["Chordoma"],"disease_names":["Chordoma"],"disease_name":"Chordoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chordoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chordoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chordoma.html#dataset-ega-egas00001006406"]},{"id":"dataset:ega:egas00001006408","accession":"ega:EGAS00001006408","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001006408","title":"Genomic landscape and molecularly-informed therapy in thymic carcinoma and other advanced thymic epithelial tumors (H021, HIPO)","alternate_titles":[],"description":"The molecular landscape of malignant thymic epithelial tumors (TET) is largely unknown. To better understand and target these clinically challenging entities, we characterize 81 patients harboring 46 thymus carcinomas (TC), 8 neuroendocrine tumors of the thymus (NET) and 27 thymomas using WGS/WES, transcriptome and methylome analysis. TC harbor different molecular alterations compared to thymoma and NET and have higher tumor mutational burden than thymomas. 14/76 TET patients show (likely) pathogenic germline alterations. Composite biomarker analysis indicates homologous repair deficiency in a subset of patients. We identify immunologically hot and cold TC.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Thymic Carcinoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Thymic_Carcinoma","name":"Thymic Carcinoma","kind":"Disorder","source_path":"kb/disorders/Thymic_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Thymic_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Thymic_Carcinoma.html#dataset-ega-egas00001006408"}],"context_names":["Thymic Carcinoma"],"disease_names":["Thymic Carcinoma"],"disease_name":"Thymic Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Thymic_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Thymic_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Thymic_Carcinoma.html#dataset-ega-egas00001006408"]},{"id":"dataset:ega:egas00001006432","accession":"ega:EGAS00001006432","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001006432","title":"Malignant mesothelioma EWAS on European prospective study","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Malignant Mesothelioma\"); description-level mentions were not accepted. EGA study_type: Epigenetics. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Malignant_Mesothelioma","name":"Malignant Mesothelioma","kind":"Disorder","source_path":"kb/disorders/Malignant_Mesothelioma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Malignant_Mesothelioma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Malignant_Mesothelioma.html#dataset-ega-egas00001006432"}],"context_names":["Malignant Mesothelioma"],"disease_names":["Malignant Mesothelioma"],"disease_name":"Malignant Mesothelioma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Malignant_Mesothelioma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Malignant_Mesothelioma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Malignant_Mesothelioma.html#dataset-ega-egas00001006432"]},{"id":"dataset:ega:egas00001006444","accession":"ega:EGAS00001006444","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001006444","title":"Airway Dysbiosis Accelerates Lung Function Decline in Chronic Obstructive Pulmonary Disease","alternate_titles":[],"description":"This repository contains human sample derived microbiome full-length 16S rRNA sequencing data for sputum samples in COPD patients. The project goal is to understand the association of the lung microbiome with accelerated lung function decline in COPD patients.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Chronic Obstructive Pulmonary Disease\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Chronic_Obstructive_Pulmonary_Disease","name":"Chronic_Obstructive_Pulmonary_Disease","kind":"Disorder","source_path":"kb/disorders/Chronic_Obstructive_Pulmonary_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Obstructive_Pulmonary_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chronic_Obstructive_Pulmonary_Disease.html#dataset-ega-egas00001006444"}],"context_names":["Chronic_Obstructive_Pulmonary_Disease"],"disease_names":["Chronic_Obstructive_Pulmonary_Disease"],"disease_name":"Chronic_Obstructive_Pulmonary_Disease","same_context_model_ids":["model:kb/disorders/Chronic_Obstructive_Pulmonary_Disease.yaml:Open-top vascularized alveolus-on-chip whole cigarette smoke model","model:kb/disorders/Chronic_Obstructive_Pulmonary_Disease.yaml:Patient-derived epithelial-endothelial COPD airway-on-a-chip"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Chronic_Obstructive_Pulmonary_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Obstructive_Pulmonary_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chronic_Obstructive_Pulmonary_Disease.html#dataset-ega-egas00001006444"]},{"id":"dataset:ega:egas00001006472","accession":"ega:EGAS00001006472","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001006472","title":"Multiple Tissue Monitoring in Huntington disease - RNAseq fibroblasts","alternate_titles":[],"description":"We examined whether peripheral tissues can serve as a source of readily accessible biological signatures at the RNA and protein level in Huntington disease (HD) patients. Under the MTM-HD study we generated large, high-quality human datasets from skeletal muscle, skin and adipose tissue, as well as primary human fibroblast lines to probe molecular changes in human pre-manifest and early manifest HD patients. We document the involvement of inflammation, energy metabolism and extracellular vesicle homeostasis. This demonstrates the potential to identify biological signatures from peripheral tissues in HD suitable as biomarkers in clinical trials.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Huntington Disease\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Huntington_Disease","name":"Huntington Disease","kind":"Disorder","source_path":"kb/disorders/Huntington_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Huntington_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Huntington_Disease.html#dataset-ega-egas00001006472"}],"context_names":["Huntington Disease"],"disease_names":["Huntington Disease"],"disease_name":"Huntington Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Huntington_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Huntington_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Huntington_Disease.html#dataset-ega-egas00001006472"]},{"id":"dataset:ega:egas00001006473","accession":"ega:EGAS00001006473","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001006473","title":"Multiple Tissue Monitoring in Huntington disease - RNAseq adipose tissue","alternate_titles":[],"description":"We examined whether peripheral tissues can serve as a source of readily accessible biological signatures at the RNA and protein level in Huntington disease (HD) patients. Under the MTM-HD study we generated large, high-quality human datasets from skeletal muscle, skin and adipose tissue, as well as primary human fibroblast lines to probe molecular changes in human pre-manifest and early manifest HD patients. We document the involvement of inflammation, energy metabolism and extracellular vesicle homeostasis. This demonstrates the potential to identify biological signatures from peripheral tissues in HD suitable as biomarkers in clinical trials.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Huntington Disease\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Huntington_Disease","name":"Huntington Disease","kind":"Disorder","source_path":"kb/disorders/Huntington_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Huntington_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Huntington_Disease.html#dataset-ega-egas00001006473"}],"context_names":["Huntington Disease"],"disease_names":["Huntington Disease"],"disease_name":"Huntington Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Huntington_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Huntington_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Huntington_Disease.html#dataset-ega-egas00001006473"]},{"id":"dataset:ega:egas00001006474","accession":"ega:EGAS00001006474","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001006474","title":"Multiple Tissue Monitoring in Huntington disease - RNAseq skeletal muscle","alternate_titles":[],"description":"We examined whether peripheral tissues can serve as a source of readily accessible biological signatures at the RNA and protein level in Huntington disease (HD) patients. Under the MTM-HD study we generated large, high-quality human datasets from skeletal muscle, skin and adipose tissue, as well as primary human fibroblast lines to probe molecular changes in human pre-manifest and early manifest HD patients. We document the involvement of inflammation, energy metabolism and extracellular vesicle homeostasis. This demonstrates the potential to identify biological signatures from peripheral tissues in HD suitable as biomarkers in clinical trials.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Huntington Disease\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Huntington_Disease","name":"Huntington Disease","kind":"Disorder","source_path":"kb/disorders/Huntington_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Huntington_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Huntington_Disease.html#dataset-ega-egas00001006474"}],"context_names":["Huntington Disease"],"disease_names":["Huntington Disease"],"disease_name":"Huntington Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Huntington_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Huntington_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Huntington_Disease.html#dataset-ega-egas00001006474"]},{"id":"dataset:ega:egas00001006519","accession":"ega:EGAS00001006519","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001006519","title":"Genetic variants of the COL4A3, COL4A4, and COL4A5 genes contribute to thinned glomerular basement membrane lesions in sporadic IgA nephropathy patients","alternate_titles":[],"description":"Contribution of pathogenic COL4A3/COL4A4/COL4A5 variants to sporadic IgAN is still unclear. Whole exome sequencing was performed in sporadic IgAN patients with thinned glomerular basement membrane lesions and variations in COL4A3/COL4A4/COL4A5 genes were screened and evaluated. 37 different diagnostic variants in COL4A3/COL4A4/COL4A5 gene in 38 patients (31.1%) were identified.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"IgA Nephropathy\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:IgA_Nephropathy","name":"IgA Nephropathy","kind":"Disorder","source_path":"kb/disorders/IgA_Nephropathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/IgA_Nephropathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/IgA_Nephropathy.html#dataset-ega-egas00001006519"}],"context_names":["IgA Nephropathy"],"disease_names":["IgA Nephropathy"],"disease_name":"IgA Nephropathy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/IgA_Nephropathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/IgA_Nephropathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/IgA_Nephropathy.html#dataset-ega-egas00001006519"]},{"id":"dataset:ega:egas00001006547","accession":"ega:EGAS00001006547","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001006547","title":"A catalog of the genetic causes of Hereditary Angioedema in the Canary Islands (Spain)","alternate_titles":[],"description":"Hereditary angioedema (HAE) is a rare disease where known causes involve C1 inhibitor dysfunction or dysregulation of the kinin cascade. The updated HAE management guidelines recommend performing genetic tests to reach a precise diagnosis. Unfortunately, genetic tests are still uncommon in the diagnosis routine. Here, we characterized for the first time the genetic causes of HAE in affected families from the Canary Islands (Spain). Whole-exome sequencing data was obtained from 41 affected patients and unaffected relatives from 29 unrelated families identified in the archipelago.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Hereditary Angioedema\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Hereditary_Angioedema","name":"Hereditary Angioedema","kind":"Disorder","source_path":"kb/disorders/Hereditary_Angioedema.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hereditary_Angioedema.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hereditary_Angioedema.html#dataset-ega-egas00001006547"}],"context_names":["Hereditary Angioedema"],"disease_names":["Hereditary Angioedema"],"disease_name":"Hereditary Angioedema","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hereditary_Angioedema.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hereditary_Angioedema.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hereditary_Angioedema.html#dataset-ega-egas00001006547"]},{"id":"dataset:ega:egas00001006631","accession":"ega:EGAS00001006631","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001006631","title":"The Genetic Landscape of Ocular Adnexa MALT Lymphoma Reveals Frequent Aberrations in NFAT and MEF2B Signaling Pathways","alternate_titles":[],"description":"A comprehensive constellation of somatic non-silent mutations and copy number (CN) variations in ocular adnexa marginal zone lymphoma (OAMZL) is unknown. By utilizing whole-exome sequencing in 69 tumors we define the genetic landscape of OAMZL. Mutations and CN changes in CABIN1 (30%), RHOA (26%), TBL1XR1 (22%), and CREBBP (17%) and inactivation of TNFAIP3 (26%) were among the most common aberrations. Candidate cancer driver genes cluster in the B-cell receptor (BCR), NFkB, NOTCH and NFAT signaling pathways. One of the most commonly altered genes is CABIN1, a calcineurin inhibitor acting as a negative regulator of the NFAT and MEF2B transcriptional activity.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"MALT Lymphoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:MALT_Lymphoma","name":"MALT Lymphoma","kind":"Disorder","source_path":"kb/disorders/MALT_Lymphoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MALT_Lymphoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/MALT_Lymphoma.html#dataset-ega-egas00001006631"}],"context_names":["MALT Lymphoma"],"disease_names":["MALT Lymphoma"],"disease_name":"MALT Lymphoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/MALT_Lymphoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MALT_Lymphoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/MALT_Lymphoma.html#dataset-ega-egas00001006631"]},{"id":"dataset:ega:egas00001006692","accession":"ega:EGAS00001006692","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001006692","title":"Pre-neoplastic liver colonization by 11p15.5 altered mosaic cells in young children with hepatoblastoma","alternate_titles":[],"description":"In children, liver tumors are a heterogeneous group representing 1-2% of all cancers with the most common diagnosis being hepatoblastoma (HB). While HBs are predominantly sporadic, around 15% of cases develop as part of predisposition syndromes such as familial adenomatous polyposis (APC mutation) or Beckwith-Wiedemann (BWS; 11p15.5 locus altered). Here, we identified a mosaic genetic alteration of 11p15.5 locus in the liver in 17% of HB patients without a clinical diagnosis of BWS syndrome. These mosaic 11p15.5 alterations were never found in children with other types of liver tumor (hepatocellular carcinoma or adenoma, fibrolamellar carcinoma).","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Hepatoblastoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Hepatoblastoma","name":"Hepatoblastoma","kind":"Disorder","source_path":"kb/disorders/Hepatoblastoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatoblastoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hepatoblastoma.html#dataset-ega-egas00001006692"}],"context_names":["Hepatoblastoma"],"disease_names":["Hepatoblastoma"],"disease_name":"Hepatoblastoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hepatoblastoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatoblastoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hepatoblastoma.html#dataset-ega-egas00001006692"]},{"id":"dataset:ega:egas00001006732","accession":"ega:EGAS00001006732","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001006732","title":"GENOMIC MUTATION LANDSCAPE OF SKIN CANCERS FROM DNA REPAIR-DEFICIENT XERODERMA PIGMENTOSUM PATIENTS","alternate_titles":[],"description":"Xeroderma pigmentosum (XP) is a genetic disorder caused by mutations in genes of the Nucleotide Excision Repair (NER) pathway (groups A-G) or in Translesion Synthesis (TLS) DNA polymerase η (group V). XP is associated with an increased skin cancer risk, reaching, for some groups, several thousand-fold compared to the general population. Here, we analyzed 38 skin cancer genomes from five XP groups. We found that the activity of NER determines heterogeneity of the mutation rates across skin cancer genomes and that transcription-coupled NER extends beyond the gene boundaries reducing the intergenic mutation rate.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Xeroderma Pigmentosum\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Xeroderma_Pigmentosum","name":"Xeroderma Pigmentosum","kind":"Disorder","source_path":"kb/disorders/Xeroderma_Pigmentosum.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Xeroderma_Pigmentosum.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Xeroderma_Pigmentosum.html#dataset-ega-egas00001006732"}],"context_names":["Xeroderma Pigmentosum"],"disease_names":["Xeroderma Pigmentosum"],"disease_name":"Xeroderma Pigmentosum","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Xeroderma_Pigmentosum.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Xeroderma_Pigmentosum.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Xeroderma_Pigmentosum.html#dataset-ega-egas00001006732"]},{"id":"dataset:ega:egas00001006795","accession":"ega:EGAS00001006795","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001006795","title":"RNA sequencing of spontaneous migraine attacks","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Migraine\"); description-level mentions were not accepted. EGA study_type: RNASeq. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Migraine","name":"Migraine","kind":"Disorder","source_path":"kb/disorders/Migraine.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Migraine.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Migraine.html#dataset-ega-egas00001006795"}],"context_names":["Migraine"],"disease_names":["Migraine"],"disease_name":"Migraine","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Migraine.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Migraine.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Migraine.html#dataset-ega-egas00001006795"]},{"id":"dataset:ega:egas00001006798","accession":"ega:EGAS00001006798","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001006798","title":"Single-cell level characterization of B cell depletion and repopulation following rituximab in systemic lupus erythematosus","alternate_titles":[],"description":"Rituximab, a CD20+ B cell depletion therapy, is frequently used in the treatment of systemic lupus erythematosus (SLE). However, variability in patient response highlights the need for a deeper understanding of the underlying immune cell dynamics of B cell depletion and repopulation. In this study, we conducted longitudinal single-cell profiling of nine SLE patients treated with rituximab from pretreatment to up to 15 months post-treatment. These were compared to eight healthy controls. We profiled PBMCs via 10X Genomics single-cell RNA, surface protein (CITE-seq), B cell receptor (BCR), and T cell receptor (TCR) sequencing and sequenced bulk BCR repertoires in parallel.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Systemic Lupus Erythematosus\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Systemic_Lupus_Erythematosus","name":"Systemic Lupus Erythematosus","kind":"Disorder","source_path":"kb/disorders/Systemic_Lupus_Erythematosus.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Systemic_Lupus_Erythematosus.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Systemic_Lupus_Erythematosus.html#dataset-ega-egas00001006798"}],"context_names":["Systemic Lupus Erythematosus"],"disease_names":["Systemic Lupus Erythematosus"],"disease_name":"Systemic Lupus Erythematosus","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Systemic_Lupus_Erythematosus.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Systemic_Lupus_Erythematosus.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Systemic_Lupus_Erythematosus.html#dataset-ega-egas00001006798"]},{"id":"dataset:ega:egas00001006926","accession":"ega:EGAS00001006926","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001006926","title":"Blood transcriptome profiling links immunity to disease severity in myotonic dystrophy type 1 (DM1).","alternate_titles":[],"description":"The blood transcriptome was examined in relation to disease severity in type I myotonic dystrophy (DM1) patients who participated in the Observational Prolonged Trial In DM1 to Improve QoL- Standards (OPTIMISTIC) study. This sought to a) ascertain if transcriptome changes were associated with increasing disease severity, as measured by the muscle impairment rating scale (MIRS) and b) es-tablish if these changes in mRNA expression and associated biological pathways were also observed in the Dystrophia Myotonica Biomarker Discovery Initiative (DMBDI) microarray dataset in blood (with equivalent MIRS/DMPK repeat length).","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Myotonic Dystrophy Type 1\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Myotonic_Dystrophy_Type_1","name":"Myotonic Dystrophy Type 1","kind":"Disorder","source_path":"kb/disorders/Myotonic_Dystrophy_Type_1.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myotonic_Dystrophy_Type_1.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Myotonic_Dystrophy_Type_1.html#dataset-ega-egas00001006926"}],"context_names":["Myotonic Dystrophy Type 1"],"disease_names":["Myotonic Dystrophy Type 1"],"disease_name":"Myotonic Dystrophy Type 1","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Myotonic_Dystrophy_Type_1.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myotonic_Dystrophy_Type_1.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Myotonic_Dystrophy_Type_1.html#dataset-ega-egas00001006926"]},{"id":"dataset:ega:egas00001006946","accession":"ega:EGAS00001006946","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001006946","title":"Genomic Analysis of a Metastatic Fusion-negative Embryonal Rhabdomyosarcoma","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Embryonal Rhabdomyosarcoma\"); description-level mentions were not accepted. EGA study_type: Cancer Genomics. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Embryonal_Rhabdomyosarcoma","name":"Embryonal Rhabdomyosarcoma","kind":"Disorder","source_path":"kb/disorders/Embryonal_Rhabdomyosarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Embryonal_Rhabdomyosarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Embryonal_Rhabdomyosarcoma.html#dataset-ega-egas00001006946"}],"context_names":["Embryonal Rhabdomyosarcoma"],"disease_names":["Embryonal Rhabdomyosarcoma"],"disease_name":"Embryonal Rhabdomyosarcoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Embryonal_Rhabdomyosarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Embryonal_Rhabdomyosarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Embryonal_Rhabdomyosarcoma.html#dataset-ega-egas00001006946"]},{"id":"dataset:ega:egas00001006948","accession":"ega:EGAS00001006948","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001006948","title":"Blood Transcriptome Profiling Links Immunity to Disease Severity in Myotonic Dystrophy Type 1 (DM1)","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Myotonic Dystrophy Type 1\"); description-level mentions were not accepted. EGA study_type: RNASeq. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Myotonic_Dystrophy_Type_1","name":"Myotonic Dystrophy Type 1","kind":"Disorder","source_path":"kb/disorders/Myotonic_Dystrophy_Type_1.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myotonic_Dystrophy_Type_1.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Myotonic_Dystrophy_Type_1.html#dataset-ega-egas00001006948"}],"context_names":["Myotonic Dystrophy Type 1"],"disease_names":["Myotonic Dystrophy Type 1"],"disease_name":"Myotonic Dystrophy Type 1","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Myotonic_Dystrophy_Type_1.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myotonic_Dystrophy_Type_1.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Myotonic_Dystrophy_Type_1.html#dataset-ega-egas00001006948"]},{"id":"dataset:ega:egas00001006970","accession":"ega:EGAS00001006970","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001006970","title":"Single-cell RNA-seq and spatial transcriptomics data for the sarcoidosis baseline project","alternate_titles":[],"description":"Granulomas are lumps of immune cells that can form in various organs. Most granulomas appear unstructured, yet they have some resemblance to lymphoid organ formation. To better understand granuloma formation, we performed single-cell sequencing and spatial transcriptomics on granulomas from patients with sarcoidosis and bioinformatically reconstructed the underlying gene-regulatory networks. We discovered an immune stimulatory environment in granulomas that repurposed transcriptional programs associated with lymphoid organ development.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Sarcoidosis\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Sarcoidosis","name":"Sarcoidosis","kind":"Disorder","source_path":"kb/disorders/Sarcoidosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sarcoidosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Sarcoidosis.html#dataset-ega-egas00001006970"}],"context_names":["Sarcoidosis"],"disease_names":["Sarcoidosis"],"disease_name":"Sarcoidosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Sarcoidosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sarcoidosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Sarcoidosis.html#dataset-ega-egas00001006970"]},{"id":"dataset:ega:egas00001007010","accession":"ega:EGAS00001007010","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001007010","title":"Whole exome sequencing in family trios reveals de novo mutations associated to Type 1 Diabetes Mellitus","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["WES"],"data_type_labels":["Whole exome sequencing"],"data_type_label":"Whole exome sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"type 1 diabetes mellitus\"); description-level mentions were not accepted. EGA study_type: Exome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Type_I_Diabetes","name":"Type I Diabetes","kind":"Disorder","source_path":"kb/disorders/Type_I_Diabetes.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Type_I_Diabetes.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Type_I_Diabetes.html#dataset-ega-egas00001007010"}],"context_names":["Type I Diabetes"],"disease_names":["Type I Diabetes"],"disease_name":"Type I Diabetes","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Type_I_Diabetes.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Type_I_Diabetes.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Type_I_Diabetes.html#dataset-ega-egas00001007010"]},{"id":"dataset:ega:egas00001007021","accession":"ega:EGAS00001007021","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001007021","title":"Single-cell dissection of the immune response after a myocardial infarction","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Myocardial Infarction\"); description-level mentions were not accepted. EGA study_type: Transcriptome Analysis. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Myocardial_Infarction","name":"Myocardial Infarction","kind":"Disorder","source_path":"kb/disorders/Myocardial_Infarction.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myocardial_Infarction.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Myocardial_Infarction.html#dataset-ega-egas00001007021"}],"context_names":["Myocardial Infarction"],"disease_names":["Myocardial Infarction"],"disease_name":"Myocardial Infarction","same_context_model_ids":["model:kb/disorders/Myocardial_Infarction.yaml:Bioelectronically instrumented heart-on-a-chip under acute hypoxia","model:kb/disorders/Myocardial_Infarction.yaml:Epicardial-myocardial heart-on-a-chip model of ischemia-reperfusion injury","model:kb/disorders/Myocardial_Infarction.yaml:Human cardiac infarct organoid with an internal oxygen-diffusion gradient","model:kb/disorders/Myocardial_Infarction.yaml:Human heart-on-a-chip ischemia-reperfusion assay with endothelial extracellular vesicle rescue","model:kb/disorders/Myocardial_Infarction.yaml:Myocardial infarct border-zone-on-a-chip"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Myocardial_Infarction.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myocardial_Infarction.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Myocardial_Infarction.html#dataset-ega-egas00001007021"]},{"id":"dataset:ega:egas00001007042","accession":"ega:EGAS00001007042","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001007042","title":"Methylation-based classification of human mesenchymal chondrosarcoma","alternate_titles":[],"description":"We applied methylome and copy number profiling to a set of 45 well characterized MCS cases to evaluate their potential diagnostic value. Notably, the findings were reproducible also when analysing the round cell and cartilaginous component separately. Furthermore, four outliers were identified by methylome profiling for which the diagnosis had to be revised. Methylome profiling represents a sensitive, specific and reliable tool to support the diagnosis of MCS, particularly if only the round cell component is obtained in a biopsy and the diagnosis is not suspected. It can furthermore aid in confirming the diagnosis in case RNA sequencing for the HEY1::NCOA2 fusion transcript is not available.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Chondrosarcoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Chondrosarcoma","name":"Chondrosarcoma","kind":"Disorder","source_path":"kb/disorders/Chondrosarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chondrosarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chondrosarcoma.html#dataset-ega-egas00001007042"}],"context_names":["Chondrosarcoma"],"disease_names":["Chondrosarcoma"],"disease_name":"Chondrosarcoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chondrosarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chondrosarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chondrosarcoma.html#dataset-ega-egas00001007042"]},{"id":"dataset:ega:egas00001007061","accession":"ega:EGAS00001007061","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001007061","title":"Germline whole genome sequencing of patients with Li-Fraumeni syndrome","alternate_titles":[],"description":"Five hundred ng to 1 ug of genomic DNA was submitted to The Centre for Applied Genomics (TCAG) at The Hospital for Sick Children for genomic library preparation and whole genome sequencing. DNA samples were quantified using the Qubit High Sensitivity Assay and purity was assessed using the Nanodrop OD 260/280 ratio. Approximately 500-700 ng of DNA was used as input material for library preparation using the Illumina TruSeq PCR-free DNA Library Prep Kit following the manufacturer’s recommended protocol. In brief, DNA was fragmented to 400 bp on average using sonication on a Covaris LE220 instrument.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Li-Fraumeni Syndrome\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Li-Fraumeni_Syndrome","name":"Li-Fraumeni Syndrome","kind":"Disorder","source_path":"kb/disorders/Li-Fraumeni_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Li-Fraumeni_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Li-Fraumeni_Syndrome.html#dataset-ega-egas00001007061"}],"context_names":["Li-Fraumeni Syndrome"],"disease_names":["Li-Fraumeni Syndrome"],"disease_name":"Li-Fraumeni Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Li-Fraumeni_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Li-Fraumeni_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Li-Fraumeni_Syndrome.html#dataset-ega-egas00001007061"]},{"id":"dataset:ega:egas00001007075","accession":"ega:EGAS00001007075","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001007075","title":"DNA methylation of peripheral blood leukocytes from patients with Li-Fraumeni syndrome","alternate_titles":[],"description":"Genomic DNA (~ 1 μg) from LFS patients was treated using sodium bisulfite (Qiagen) converting unmethylated cytosine to uracil but leaving methylated cytosine intact. These samples were then hybridized to the HumanMethylation450 BeadChip or HumanMethylationEPIC BeadChip from Illumina at the Centre for Applied Genomics (TCAG) at the Hospital for Sick Children using the manufacturer’s recommended protocol.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Li-Fraumeni Syndrome\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Li-Fraumeni_Syndrome","name":"Li-Fraumeni Syndrome","kind":"Disorder","source_path":"kb/disorders/Li-Fraumeni_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Li-Fraumeni_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Li-Fraumeni_Syndrome.html#dataset-ega-egas00001007075"}],"context_names":["Li-Fraumeni Syndrome"],"disease_names":["Li-Fraumeni Syndrome"],"disease_name":"Li-Fraumeni Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Li-Fraumeni_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Li-Fraumeni_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Li-Fraumeni_Syndrome.html#dataset-ega-egas00001007075"]},{"id":"dataset:ega:egas00001007079","accession":"ega:EGAS00001007079","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001007079","title":"Transgenerational transmission of reproductive and metabolic dysfunction in the male progeny of polycystic ovary syndrome","alternate_titles":[],"description":"The transgenerational maternal effects of PCOS in female progeny have been revealed. As there are evidence that a male equivalent of PCOS may exist, we asked whether sons born to mother with PCOS (PCOS-sons) transmit reproductive and metabolic phenotypes to their male progeny. Here, in a Swedish nationwide register-based cohort and a clinical case-control study from Chile we found that PCOS-sons are more often obese and dyslipidemic. Their serum miRNAs are found to potentially regulate PCOS-risk genes. Our prenatal androgenized PCOS-like mouse model with or without diet-induced obesity confirmed that reproductive and metabolic dysfunctions in F1 male offspring are passed down to F3.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Polycystic Ovary Syndrome\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Polycystic_Ovary_Syndrome","name":"Polycystic Ovary Syndrome","kind":"Disorder","source_path":"kb/disorders/Polycystic_Ovary_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Polycystic_Ovary_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Polycystic_Ovary_Syndrome.html#dataset-ega-egas00001007079"}],"context_names":["Polycystic Ovary Syndrome"],"disease_names":["Polycystic Ovary Syndrome"],"disease_name":"Polycystic Ovary Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Polycystic_Ovary_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Polycystic_Ovary_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Polycystic_Ovary_Syndrome.html#dataset-ega-egas00001007079"]},{"id":"dataset:ega:egas00001007117","accession":"ega:EGAS00001007117","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001007117","title":"Identification of Long Non-coding RNA Biomarker of Human Lupus Nephritis Disease Activity","alternate_titles":[],"description":"Total RNA sequencing was performed on whole blood samples from 74 Lupus nephritis (LN) patients and 20 healthy controls. Differential expression analysis and weighted gene co-expression network analysis were performed to characterise expression changes of long non-coding RNAs (lncRNAs) in LN and identify lncRNAs with a key role in disease activity that could be used as potential blood-based biomarkers.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Lupus Nephritis\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Lupus_Nephritis","name":"Lupus Nephritis","kind":"Disorder","source_path":"kb/disorders/Lupus_Nephritis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Lupus_Nephritis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Lupus_Nephritis.html#dataset-ega-egas00001007117"}],"context_names":["Lupus Nephritis"],"disease_names":["Lupus Nephritis"],"disease_name":"Lupus Nephritis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Lupus_Nephritis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Lupus_Nephritis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Lupus_Nephritis.html#dataset-ega-egas00001007117"]},{"id":"dataset:ega:egas00001007257","accession":"ega:EGAS00001007257","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001007257","title":"Methylome profiling of epithelioid sarcoma","alternate_titles":[],"description":"Explore the methylome landscape of epithelioid sarcoma using array data.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Epithelioid Sarcoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Epithelioid_Sarcoma","name":"Epithelioid Sarcoma","kind":"Disorder","source_path":"kb/disorders/Epithelioid_Sarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Epithelioid_Sarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Epithelioid_Sarcoma.html#dataset-ega-egas00001007257"}],"context_names":["Epithelioid Sarcoma"],"disease_names":["Epithelioid Sarcoma"],"disease_name":"Epithelioid Sarcoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Epithelioid_Sarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Epithelioid_Sarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Epithelioid_Sarcoma.html#dataset-ega-egas00001007257"]},{"id":"dataset:ega:egas00001007264","accession":"ega:EGAS00001007264","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001007264","title":"Molecular EPISTOP: Comprehensive multi-omic analysis of blood from Tuberous Sclerosis Complex infants age birth to two years","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Tuberous Sclerosis Complex\"); description-level mentions were not accepted. EGA study_type: RNASeq. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Tuberous_Sclerosis_Complex","name":"Tuberous Sclerosis Complex","kind":"Disorder","source_path":"kb/disorders/Tuberous_Sclerosis_Complex.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Tuberous_Sclerosis_Complex.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Tuberous_Sclerosis_Complex.html#dataset-ega-egas00001007264"}],"context_names":["Tuberous Sclerosis Complex"],"disease_names":["Tuberous Sclerosis Complex"],"disease_name":"Tuberous Sclerosis Complex","same_context_model_ids":["model:kb/disorders/Tuberous_Sclerosis_Complex.yaml:CRISPR-engineered TSC2 conditional-biallelic human cortical spheroids","model:kb/disorders/Tuberous_Sclerosis_Complex.yaml:TSC human cerebral organoids with caudal late interneuron progenitor (CLIP) over-proliferation","model:kb/disorders/Tuberous_Sclerosis_Complex.yaml:TSC patient-derived neurovascular unit (iPSC blood-brain-barrier chip)"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Tuberous_Sclerosis_Complex.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Tuberous_Sclerosis_Complex.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Tuberous_Sclerosis_Complex.html#dataset-ega-egas00001007264"]},{"id":"dataset:ega:egas00001007294","accession":"ega:EGAS00001007294","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001007294","title":"Genomics-based characterization and personalized treatment in pleural and peritoneal mesothelioma","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Peritoneal Mesothelioma\"); description-level mentions were not accepted. EGA study_type: Cancer Genomics. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Malignant_Peritoneal_Mesothelioma","name":"Malignant Peritoneal Mesothelioma","kind":"Disorder","source_path":"kb/disorders/Malignant_Peritoneal_Mesothelioma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Malignant_Peritoneal_Mesothelioma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Malignant_Peritoneal_Mesothelioma.html#dataset-ega-egas00001007294"}],"context_names":["Malignant Peritoneal Mesothelioma"],"disease_names":["Malignant Peritoneal Mesothelioma"],"disease_name":"Malignant Peritoneal Mesothelioma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Malignant_Peritoneal_Mesothelioma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Malignant_Peritoneal_Mesothelioma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Malignant_Peritoneal_Mesothelioma.html#dataset-ega-egas00001007294"]},{"id":"dataset:ega:egas00001007350","accession":"ega:EGAS00001007350","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001007350","title":"A circulating biomarker for severity of facioscapulohumeral muscular dystrophy","alternate_titles":[],"description":"Facioscapulohumeral muscular dystrophy (FSHD) is a prevalent, incurable skeletal myopathy. Clinical trials for FSHD are hindered by heterogeneous biomarkers poorly associated with clinical severity, requiring invasive muscle biopsy. Macroscopically FSHD presents with slow fatty replacement of muscle, rapidly accelerated by inflammation. Mis-expression of the transcription factor DUX4 is currently accepted to underlie FSHD pathogenesis and mechanisms including PAX7 target gene repression have been proposed.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Facioscapulohumeral Muscular Dystrophy\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Facioscapulohumeral_Muscular_Dystrophy","name":"Facioscapulohumeral Muscular Dystrophy","kind":"Disorder","source_path":"kb/disorders/Facioscapulohumeral_Muscular_Dystrophy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Facioscapulohumeral_Muscular_Dystrophy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Facioscapulohumeral_Muscular_Dystrophy.html#dataset-ega-egas00001007350"}],"context_names":["Facioscapulohumeral Muscular Dystrophy"],"disease_names":["Facioscapulohumeral Muscular Dystrophy"],"disease_name":"Facioscapulohumeral Muscular Dystrophy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Facioscapulohumeral_Muscular_Dystrophy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Facioscapulohumeral_Muscular_Dystrophy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Facioscapulohumeral_Muscular_Dystrophy.html#dataset-ega-egas00001007350"]},{"id":"dataset:ega:egas00001007370","accession":"ega:EGAS00001007370","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001007370","title":"Sclerosing Epithelioid Fibrosarcoma sequencing data","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Fibrosarcoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Fibrosarcoma","name":"Fibrosarcoma","kind":"Disorder","source_path":"kb/disorders/Fibrosarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fibrosarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Fibrosarcoma.html#dataset-ega-egas00001007370"}],"context_names":["Fibrosarcoma"],"disease_names":["Fibrosarcoma"],"disease_name":"Fibrosarcoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Fibrosarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fibrosarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Fibrosarcoma.html#dataset-ega-egas00001007370"]},{"id":"dataset:ega:egas00001007388","accession":"ega:EGAS00001007388","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001007388","title":"Whole-genome sequencing of twins with Castleman disease and an unaffected sibling.","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Castleman Disease\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Idiopathic_Multicentric_Castleman_Disease","name":"Idiopathic Multicentric Castleman Disease","kind":"Disorder","source_path":"kb/disorders/Idiopathic_Multicentric_Castleman_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Idiopathic_Multicentric_Castleman_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Idiopathic_Multicentric_Castleman_Disease.html#dataset-ega-egas00001007388"}],"context_names":["Idiopathic Multicentric Castleman Disease"],"disease_names":["Idiopathic Multicentric Castleman Disease"],"disease_name":"Idiopathic Multicentric Castleman Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Idiopathic_Multicentric_Castleman_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Idiopathic_Multicentric_Castleman_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Idiopathic_Multicentric_Castleman_Disease.html#dataset-ega-egas00001007388"]},{"id":"dataset:ega:egas00001007390","accession":"ega:EGAS00001007390","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001007390","title":"Single cell landscape of Multicentric Castleman Disease in monozygotic twins","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Castleman Disease\"); description-level mentions were not accepted. EGA study_type: Whole Genome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Idiopathic_Multicentric_Castleman_Disease","name":"Idiopathic Multicentric Castleman Disease","kind":"Disorder","source_path":"kb/disorders/Idiopathic_Multicentric_Castleman_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Idiopathic_Multicentric_Castleman_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Idiopathic_Multicentric_Castleman_Disease.html#dataset-ega-egas00001007390"}],"context_names":["Idiopathic Multicentric Castleman Disease"],"disease_names":["Idiopathic Multicentric Castleman Disease"],"disease_name":"Idiopathic Multicentric Castleman Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Idiopathic_Multicentric_Castleman_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Idiopathic_Multicentric_Castleman_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Idiopathic_Multicentric_Castleman_Disease.html#dataset-ega-egas00001007390"]},{"id":"dataset:ega:egas00001007487","accession":"ega:EGAS00001007487","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001007487","title":"Optimizing single-cell transcriptomic discrimination of atopic dermatitis versus psoriasis vulgaris","alternate_titles":[],"description":"Optimizing single-cell transcriptomic discrimination of atopic dermatitis versus psoriasis vulgaris","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Atopic Dermatitis\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Atopic_Dermatitis","name":"Atopic Dermatitis","kind":"Disorder","source_path":"kb/disorders/Atopic_Dermatitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Atopic_Dermatitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Atopic_Dermatitis.html#dataset-ega-egas00001007487"}],"context_names":["Atopic Dermatitis"],"disease_names":["Atopic Dermatitis"],"disease_name":"Atopic Dermatitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Atopic_Dermatitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Atopic_Dermatitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Atopic_Dermatitis.html#dataset-ega-egas00001007487"]},{"id":"dataset:ega:egas00001007527","accession":"ega:EGAS00001007527","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001007527","title":"Evolutionary trajectories of IDH-mutant astrocytoma identify molecular grading markers related to cell cycling","alternate_titles":[],"description":"To study the evolutionary processes that drive malignant transformation in IDH-mutant astrocytomas, we performed multi-omics on a large cohort of matched initial and recurrent tumor samples. We find that genome-wide DNA-methylation levels decreased over time, mainly in patients with high-grade recurrences. DNA-demethylation was lifted from specific loci associated with DNA replication, and was associated with upregulation of cell cycling associated genes. Upregulation of cell cycling genes occurred predominantly in proliferating tumor cells, and was associated with tumor grade.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"IDH-Mutant Astrocytoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:IDH_Mutant_Astrocytoma","name":"IDH-Mutant Astrocytoma","kind":"Disorder","source_path":"kb/disorders/IDH_Mutant_Astrocytoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/IDH_Mutant_Astrocytoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/IDH-Mutant_Astrocytoma.html#dataset-ega-egas00001007527"}],"context_names":["IDH-Mutant Astrocytoma"],"disease_names":["IDH-Mutant Astrocytoma"],"disease_name":"IDH-Mutant Astrocytoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/IDH_Mutant_Astrocytoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/IDH_Mutant_Astrocytoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/IDH-Mutant_Astrocytoma.html#dataset-ega-egas00001007527"]},{"id":"dataset:ega:egas00001007557","accession":"ega:EGAS00001007557","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001007557","title":"WGS data of an individual with Unicentric Castleman Disease","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["WGS"],"data_type_labels":["Whole genome sequencing"],"data_type_label":"Whole genome sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Castleman Disease\"); description-level mentions were not accepted. 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BCR/TCR features were heterogeneous, and BCR measures describing clonal expansion demonstrated independent prognostic value.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"HER2-Positive Breast Cancer\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:HER2_Positive_Breast_Cancer","name":"HER2-Positive Breast Cancer","kind":"Disorder","source_path":"kb/disorders/HER2_Positive_Breast_Cancer.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/HER2_Positive_Breast_Cancer.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/HER2-Positive_Breast_Cancer.html#dataset-ega-egas00001007563"}],"context_names":["HER2-Positive Breast Cancer"],"disease_names":["HER2-Positive Breast Cancer"],"disease_name":"HER2-Positive Breast Cancer","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/HER2_Positive_Breast_Cancer.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/HER2_Positive_Breast_Cancer.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/HER2-Positive_Breast_Cancer.html#dataset-ega-egas00001007563"]},{"id":"dataset:ega:egas00001007700","accession":"ega:EGAS00001007700","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001007700","title":"GWAS membranous nephropathy Stanescu et al., 2011 UK cohort, chr2 region of interest, imputed","alternate_titles":[],"description":"334 biopsy-confirmed membranous nephropathy (MN) cases and 349 ethnically matched healthy controls: the British cohort of the Stanescu et al., 2011 GWAS. 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EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Membranous_Nephropathy","name":"Membranous nephropathy","kind":"Disorder","source_path":"kb/disorders/Membranous_Nephropathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Membranous_Nephropathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Membranous_nephropathy.html#dataset-ega-egas00001007700"}],"context_names":["Membranous nephropathy"],"disease_names":["Membranous nephropathy"],"disease_name":"Membranous nephropathy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Membranous_Nephropathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Membranous_Nephropathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Membranous_nephropathy.html#dataset-ega-egas00001007700"]},{"id":"dataset:ega:egas00001007844","accession":"ega:EGAS00001007844","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001007844","title":"Array-based methylation analysis of SDHB-deficient pheochromocytoma and paraganglioma","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Pheochromocytoma and Paraganglioma\"); description-level mentions were not accepted. EGA study_type: Cancer Genomics. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Pheochromocytoma_Paraganglioma","name":"Pheochromocytoma and Paraganglioma","kind":"Disorder","source_path":"kb/disorders/Pheochromocytoma_Paraganglioma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pheochromocytoma_Paraganglioma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pheochromocytoma_and_Paraganglioma.html#dataset-ega-egas00001007844"}],"context_names":["Pheochromocytoma and Paraganglioma"],"disease_names":["Pheochromocytoma and Paraganglioma"],"disease_name":"Pheochromocytoma and Paraganglioma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Pheochromocytoma_Paraganglioma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pheochromocytoma_Paraganglioma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Pheochromocytoma_and_Paraganglioma.html#dataset-ega-egas00001007844"]},{"id":"dataset:ega:egas00001007904","accession":"ega:EGAS00001007904","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001007904","title":"Tubulointerstitial fibrosis is the histological hallmark of chronic kidney disease (CKD). Hypoxia and inflammation (i.e., interleukin (IL)-1β signalling) are independent mediators of tubulointerstitial fibrosis. However, the physiological response of human kidney tubular cells to IL-1β/IL-1RI signalling under the hypoxic conditions of CKD is poorly understood and remains a clinical imperative for therapeutic targeting. This study reports that hypoxia and IL-1β act in synergy to trigger cell cycle arrest/cellular senescence of ex vivo patient-derived primary proximal tubular epithelial cells (PTECs).","alternate_titles":[],"description":"Hypoxia and interleukin (IL)-1β are independent mediators of tubulointerstitial fibrosis, the histological hallmark of chronic kidney disease (CKD). Here, we examine how hypoxia and IL-1β act in synergy to augment maladaptive proximal tubular epithelial cell (PTEC) repair in human CKD. Ex vivo patient-derived PTECs were cultured under normoxic (21% O2) or hypoxic (1% O2) conditions in the absence or presence of IL-1β and examined for maladaptive repair signatures. Hypoxic PTECs incubated with IL-1β displayed a discrete transcriptomic profile distinct from PTECs cultured under hypoxia alone, IL-1β alone or under normoxia.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Chronic Kidney Disease\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Chronic_Kidney_Disease","name":"Chronic Kidney Disease","kind":"Disorder","source_path":"kb/disorders/Chronic_Kidney_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Kidney_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chronic_Kidney_Disease.html#dataset-ega-egas00001007904"}],"context_names":["Chronic Kidney Disease"],"disease_names":["Chronic Kidney Disease"],"disease_name":"Chronic Kidney Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chronic_Kidney_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Kidney_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chronic_Kidney_Disease.html#dataset-ega-egas00001007904"]},{"id":"dataset:ega:egas00001007934","accession":"ega:EGAS00001007934","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001007934","title":"Multi-Layered Molecular Profiling Informs the Diagnosis and Targeted Therapy of Desmoplastic Small Round Cell Tumor","alternate_titles":[],"description":"Desmoplastic small round cell tumor (DSRCT) is an ultra-rare soft tissue sarcoma with dismal prognosis and limited therapeutic options. Here, we identified individual therapeutic targets in a cohort of 30 DSRCT patients by use of multilayered molecular profiling (genomic, transcriptomic, and (phospho-)proteomic analyses) within the DKFZ NCT DKTK MASTER program. 28 of the 30 patients received at least one personalized treatment recommendation. In line with the observation that DSRCTs are an entity with a low mutational load, most of the treatment recommendations were based on target gene or -protein expression.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Desmoplastic Small Round Cell Tumor\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Desmoplastic_Small_Round_Cell_Tumor","name":"Desmoplastic Small Round Cell Tumor","kind":"Disorder","source_path":"kb/disorders/Desmoplastic_Small_Round_Cell_Tumor.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Desmoplastic_Small_Round_Cell_Tumor.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Desmoplastic_Small_Round_Cell_Tumor.html#dataset-ega-egas00001007934"}],"context_names":["Desmoplastic Small Round Cell Tumor"],"disease_names":["Desmoplastic Small Round Cell Tumor"],"disease_name":"Desmoplastic Small Round Cell Tumor","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Desmoplastic_Small_Round_Cell_Tumor.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Desmoplastic_Small_Round_Cell_Tumor.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Desmoplastic_Small_Round_Cell_Tumor.html#dataset-ega-egas00001007934"]},{"id":"dataset:ega:egas00001007985","accession":"ega:EGAS00001007985","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001007985","title":"CDK4/6 inhibition in advanced chordoma: final results of the NCT PMO-1601","alternate_titles":[],"description":"Background. Chordoma is a rare bone tumor with no approved systemic therapy. Inactivation of the tumor suppressor p16 (encoded by CDKN2A) leads to aberrant cyclin D-CDK4/6-RB pathway activity, which can be inhibited by palbociclib in chordoma cell lines. Patients and Methods. We conducted a phase II single-arm, open-labeled trial on palbociclib in adult patients with advanced chordomas with p16 loss (by immunohistochemistry) or CDKN2A loss (by genomic analysis) and CDK4/6 and RB1 presence (by immunohistochemistry or RNA-Sequencing). Patients received 125mg palbociclib once daily for 21 days in a 28-day cycle. The study used a Simon optimal 2-stage design.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Chordoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Chordoma","name":"Chordoma","kind":"Disorder","source_path":"kb/disorders/Chordoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chordoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chordoma.html#dataset-ega-egas00001007985"}],"context_names":["Chordoma"],"disease_names":["Chordoma"],"disease_name":"Chordoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chordoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chordoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chordoma.html#dataset-ega-egas00001007985"]},{"id":"dataset:ega:egas00001008059","accession":"ega:EGAS00001008059","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001008059","title":"Beyond BRCA deficiency: Clinical and molecular predictors of survival in patients with BRCA-deficient tubo-ovarian high-grade serous carcinoma","alternate_titles":[],"description":"Homologous recombination DNA repair deficient (HRD) tumors account for about 50% of tubo-ovarian high-grade serous carcinomas (HGSC) and are associated with a high response to platinum-based chemotherapy. However, a subset of patients with HRD tumors have unexpected resistance to chemotherapy and experience short survival. Our study compared BRCA-deficient and proficient HGSC among patients with short (<3 years, the lowest quartile of overall survival (OS)) versus longer-term (>3 year OS) to identify prognostic markers and potential therapeutic opportunities.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Ovarian High-Grade Serous Carcinoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Ovarian_High-Grade_Serous_Carcinoma","name":"Ovarian High-Grade Serous Carcinoma","kind":"Disorder","source_path":"kb/disorders/Ovarian_High-Grade_Serous_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ovarian_High-Grade_Serous_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Ovarian_High-Grade_Serous_Carcinoma.html#dataset-ega-egas00001008059"}],"context_names":["Ovarian High-Grade Serous Carcinoma"],"disease_names":["Ovarian High-Grade Serous Carcinoma"],"disease_name":"Ovarian High-Grade Serous Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Ovarian_High-Grade_Serous_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ovarian_High-Grade_Serous_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Ovarian_High-Grade_Serous_Carcinoma.html#dataset-ega-egas00001008059"]},{"id":"dataset:ega:egas00001008106","accession":"ega:EGAS00001008106","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001008106","title":"Spatial and multi-omic profiling reveals genes and pathways associated with cytotoxic lymphocyte infiltration in malignant rhabdoid tumor","alternate_titles":[],"description":"Malignant rhabdoid tumors (MRTs) are aggressive pediatric cancers with poor outcomes. MRTs exhibit low tumor mutational burden, yet recent studies reported immune cell infiltration. Here, we used spatial transcriptomics and multi-omics to explore molecular and cellular features associated with immune cell infiltration in MRT. We identified a diverse set of tumor antigens (TAs) expressed by MRT cells and showed that genes associated with the IRF1 signaling pathway and antigen processing/presentation are significantly correlated with cytotoxic lymphocyte infiltration.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Rhabdoid Tumor\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Rhabdoid_Tumor","name":"Rhabdoid Tumor","kind":"Disorder","source_path":"kb/disorders/Rhabdoid_Tumor.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rhabdoid_Tumor.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Rhabdoid_Tumor.html#dataset-ega-egas00001008106"}],"context_names":["Rhabdoid Tumor"],"disease_names":["Rhabdoid Tumor"],"disease_name":"Rhabdoid Tumor","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Rhabdoid_Tumor.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rhabdoid_Tumor.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Rhabdoid_Tumor.html#dataset-ega-egas00001008106"]},{"id":"dataset:ega:egas00001008108","accession":"ega:EGAS00001008108","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001008108","title":"A cycling, progenitor-like cell population at the root of atypical teratoid rhabdoid tumor subtype differentiation trajectories.","alternate_titles":[],"description":"Background: Atypical teratoid rhabdoid tumors (ATRTs), characterized by the loss of SMARCB1, are among the most lethal pediatric central nervous system (CNS) tumors. Three molecular subtypes have been identified, each defined by distinct molecular and clinical features. No subtype-specific treatments are available, highlighting the necessity to better understand inter- and intra-subtype heterogeneity. Methods: We generated a single-nucleus transcriptome atlas of ATRTs, validated by single-cell ATAC-seq and spatial transcriptomics, to study subtype-specific differentiation trajectories.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"atypical teratoid rhabdoid tumor\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.","European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Rhabdoid Tumor\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Atypical_Teratoid_Rhabdoid_Tumor","name":"Atypical Teratoid/Rhabdoid Tumor","kind":"Disorder","source_path":"kb/disorders/Atypical_Teratoid_Rhabdoid_Tumor.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Atypical_Teratoid_Rhabdoid_Tumor.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Atypical_Teratoid_Rhabdoid_Tumor.html#dataset-ega-egas00001008108"},{"id":"disorder:Rhabdoid_Tumor","name":"Rhabdoid Tumor","kind":"Disorder","source_path":"kb/disorders/Rhabdoid_Tumor.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rhabdoid_Tumor.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Rhabdoid_Tumor.html#dataset-ega-egas00001008108"}],"context_names":["Atypical Teratoid/Rhabdoid Tumor","Rhabdoid Tumor"],"disease_names":["Atypical Teratoid/Rhabdoid Tumor","Rhabdoid Tumor"],"disease_name":"Atypical Teratoid/Rhabdoid Tumor","same_context_model_ids":["model:kb/disorders/Atypical_Teratoid_Rhabdoid_Tumor.yaml:Patient-derived AT/RT tumoroids"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Atypical_Teratoid_Rhabdoid_Tumor.yaml","kb/disorders/Rhabdoid_Tumor.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Atypical_Teratoid_Rhabdoid_Tumor.yaml","https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rhabdoid_Tumor.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Atypical_Teratoid_Rhabdoid_Tumor.html#dataset-ega-egas00001008108","https://dismech.monarchinitiative.org/pages/disorders/Rhabdoid_Tumor.html#dataset-ega-egas00001008108"]},{"id":"dataset:ega:egas00001008123","accession":"ega:EGAS00001008123","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001008123","title":"A cycling, progenitor-like cell population at the root of atypical teratoid rhabdoid tumor subtype differentiation trajectories","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"atypical teratoid rhabdoid tumor\"); description-level mentions were not accepted. EGA study_type: Cancer Genomics. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Atypical_Teratoid_Rhabdoid_Tumor","name":"Atypical Teratoid/Rhabdoid Tumor","kind":"Disorder","source_path":"kb/disorders/Atypical_Teratoid_Rhabdoid_Tumor.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Atypical_Teratoid_Rhabdoid_Tumor.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Atypical_Teratoid_Rhabdoid_Tumor.html#dataset-ega-egas00001008123"}],"context_names":["Atypical Teratoid/Rhabdoid Tumor"],"disease_names":["Atypical Teratoid/Rhabdoid Tumor"],"disease_name":"Atypical Teratoid/Rhabdoid Tumor","same_context_model_ids":["model:kb/disorders/Atypical_Teratoid_Rhabdoid_Tumor.yaml:Patient-derived AT/RT tumoroids"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Atypical_Teratoid_Rhabdoid_Tumor.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Atypical_Teratoid_Rhabdoid_Tumor.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Atypical_Teratoid_Rhabdoid_Tumor.html#dataset-ega-egas00001008123"]},{"id":"dataset:ega:egas00001008157","accession":"ega:EGAS00001008157","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001008157","title":"High-Resolution Spatial Transcriptomics Uncover Epidermal-Dermal Divergences in Merkel Cell Carcinoma: Spatial Context Reshapes the Gene Expression Landscape","alternate_titles":[],"description":"Merkel cell carcinoma (MCC) is an aggressive malignancy with neuroendocrine differentiation marked by high plasticity, often manifesting as rapid therapy resistance. Although the cell-of-origin is presumed to be epithelial, epidermal localization of MCC is rarely observed, largely because in situ MCC is typically an incidental finding. Nevertheless, a subset of MCC tumors exhibits epidermotropism, wherein tumor cells are present in the epidermis. The behavior of cancer cells is profoundly influenced by the tumor microenvironment and interactions with neighboring cells. Notably, the normal counterparts of the cancer’s cell-of-origin have been shown to attenuate tumor aggressiveness.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Merkel Cell Carcinoma\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Merkel_Cell_Carcinoma","name":"Merkel Cell Carcinoma","kind":"Disorder","source_path":"kb/disorders/Merkel_Cell_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Merkel_Cell_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Merkel_Cell_Carcinoma.html#dataset-ega-egas00001008157"}],"context_names":["Merkel Cell Carcinoma"],"disease_names":["Merkel Cell Carcinoma"],"disease_name":"Merkel Cell Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Merkel_Cell_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Merkel_Cell_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Merkel_Cell_Carcinoma.html#dataset-ega-egas00001008157"]},{"id":"dataset:ega:egas00001008306","accession":"ega:EGAS00001008306","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001008306","title":"Toward PRecisiOn Medicine for the Prediction of Treatment Response in Major Depressive Disorder through Stratification of Combined Clinical and Omics Signatures","alternate_titles":[],"description":"Major depressive disorder (MDD) is the most common psychiatric disorder worldwide. Pharmacotherapy is the standard first-line treatment, yet only one third of patients respond to the initial trial and about 30% develop treatment-resistant depression (TRD), which is associated with specific clinical and molecular features. The PROMPT project aims to develop a precision medicine algorithm for early identification of non-responders.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Major Depressive Disorder\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Major_Depressive_Disorder","name":"Major Depressive Disorder","kind":"Disorder","source_path":"kb/disorders/Major_Depressive_Disorder.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Major_Depressive_Disorder.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Major_Depressive_Disorder.html#dataset-ega-egas00001008306"}],"context_names":["Major Depressive Disorder"],"disease_names":["Major Depressive Disorder"],"disease_name":"Major Depressive Disorder","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Major_Depressive_Disorder.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Major_Depressive_Disorder.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Major_Depressive_Disorder.html#dataset-ega-egas00001008306"]},{"id":"dataset:ega:egas00001008347","accession":"ega:EGAS00001008347","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001008347","title":"Genetic and Genomic Landscape of Hemochromatosis Hepatocellular Carcinoma","alternate_titles":[],"description":"Hemochromatosis is a Mendelian genetic disorder characterized by systemic iron overload, which increases the risk of developing hepatocellular carcinoma (HCC). This study aims to investigate the genetic and molecular mechanisms underlying HCC in patients with hemochromatosis, to improve understanding of disease progression and identify potential therapeutic targets","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Hemochromatosis\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Hemochromatosis","name":"Hemochromatosis","kind":"Disorder","source_path":"kb/disorders/Hemochromatosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hemochromatosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hemochromatosis.html#dataset-ega-egas00001008347"}],"context_names":["Hemochromatosis"],"disease_names":["Hemochromatosis"],"disease_name":"Hemochromatosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hemochromatosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hemochromatosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hemochromatosis.html#dataset-ega-egas00001008347"]},{"id":"dataset:ega:egas00001008389","accession":"ega:EGAS00001008389","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS00001008389","title":"Microarray raw data on Chronic Thromboembolic Pulmonary Hypertension (CTEPH) endothelial cells, and a healthy control patients group","alternate_titles":[],"description":"Microarray raw data on Chronic Thromboembolic Pulmonary Hypertension (CTEPH) endothelial cells, and a healthy control patients group","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Pulmonary hypertension\"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Pulmonary_hypertension","name":"Pulmonary_hypertension","kind":"Disorder","source_path":"kb/disorders/Pulmonary_hypertension.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pulmonary_hypertension.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pulmonary_hypertension.html#dataset-ega-egas00001008389"}],"context_names":["Pulmonary_hypertension"],"disease_names":["Pulmonary_hypertension"],"disease_name":"Pulmonary_hypertension","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Pulmonary_hypertension.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pulmonary_hypertension.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Pulmonary_hypertension.html#dataset-ega-egas00001008389"]},{"id":"dataset:ega:egas50000000026","accession":"ega:EGAS50000000026","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000000026","title":"Methylome profiling of Solitary fibrous tumor/Hemangiopericytoma (SFT/HPC) and a patient derived cell-line model","alternate_titles":[],"description":"Solitary fibrous tumor/Hemangiopericytoma (SFT/HPC) is a rare subtype of soft tissue sarcoma associated with NAB2-STAT6 gene fusions. This study established and characterized a novel SFT/HPC patient-derived cell line called SFT-S1 using the twist human methylome panel.","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Solitary Fibrous Tumor\"); description-level mentions were not accepted. EGA study_type: Epigenetics. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Solitary_Fibrous_Tumor","name":"Solitary Fibrous Tumor","kind":"Disorder","source_path":"kb/disorders/Solitary_Fibrous_Tumor.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Solitary_Fibrous_Tumor.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Solitary_Fibrous_Tumor.html#dataset-ega-egas50000000026"}],"context_names":["Solitary Fibrous Tumor"],"disease_names":["Solitary Fibrous Tumor"],"disease_name":"Solitary Fibrous Tumor","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Solitary_Fibrous_Tumor.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Solitary_Fibrous_Tumor.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Solitary_Fibrous_Tumor.html#dataset-ega-egas50000000026"]},{"id":"dataset:ega:egas50000000049","accession":"ega:EGAS50000000049","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000000049","title":"NGS on cardiac samples in Hungarian patients of dilated cardiomyopathy","alternate_titles":[],"description":"Heterozygous (HET) truncating mutations in the TTN gene (TTNtv) encoding the giant titin protein are the most common genetic cause of dilated cardiomyopathy (DCM). We investigated 127 clinically identified DCM human cardiac samples with targeted sequencing using the TruSight Cardio panel on an Illumina MiSeq system with a special focus on TTNtvs.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Dilated Cardiomyopathy\"); description-level mentions were not accepted. EGA study_type: Resequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Dilated_Cardiomyopathy","name":"Dilated Cardiomyopathy","kind":"Disorder","source_path":"kb/disorders/Dilated_Cardiomyopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dilated_Cardiomyopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy.html#dataset-ega-egas50000000049"}],"context_names":["Dilated Cardiomyopathy"],"disease_names":["Dilated Cardiomyopathy"],"disease_name":"Dilated Cardiomyopathy","same_context_model_ids":["model:kb/disorders/Dilated_Cardiomyopathy.yaml:Patient-specific TNNT2 R173W iPSC-derived cardiomyocytes (Clinical Trials in a Dish)"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Dilated_Cardiomyopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dilated_Cardiomyopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy.html#dataset-ega-egas50000000049"]},{"id":"dataset:ega:egas50000000061","accession":"ega:EGAS50000000061","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000000061","title":"Identification of germline variants in Medullary thyroid carcinoma (MTC) by whole- exome sequencing","alternate_titles":[],"description":"Medullary thyroid cancer (MTC) is a rare malignant tumor that arises from parafollicular cells. Approximately 8% of thyroid cancer cases are MTC, and about 25% of these have a hereditary component. Incorporating molecular parameters into tumor classification is important. Besides, the presence of pathogenic germline variants can impact directly on cancer prevention. Thus, the aim of this study was to perform whole exome sequencing (WES) on a consecutive series of hereditary RET wild-type MTC patients to identify genetic variants that may be involved in the carcinogenesis of this tumor.","alternate_descriptions":[],"data_types":["WES"],"data_type_labels":["Whole exome sequencing"],"data_type_label":"Whole exome sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Medullary Thyroid Carcinoma\"); description-level mentions were not accepted. EGA study_type: Exome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Medullary_Thyroid_Carcinoma","name":"Medullary Thyroid Carcinoma","kind":"Disorder","source_path":"kb/disorders/Medullary_Thyroid_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Medullary_Thyroid_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Medullary_Thyroid_Carcinoma.html#dataset-ega-egas50000000061"}],"context_names":["Medullary Thyroid Carcinoma"],"disease_names":["Medullary Thyroid Carcinoma"],"disease_name":"Medullary Thyroid Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Medullary_Thyroid_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Medullary_Thyroid_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Medullary_Thyroid_Carcinoma.html#dataset-ega-egas50000000061"]},{"id":"dataset:ega:egas50000000101","accession":"ega:EGAS50000000101","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000000101","title":"WNT-dependent interaction between inflammatory fibroblasts and FOLR2+ macrophages promotes fibrosis in chronic kidney disease","alternate_titles":[],"description":"Chronic kidney disease (CKD) is a public health problem driven by myofibroblast accumulation, leading to interstitial fibrosis. Heterogeneity is a recently recognised characteristics in kidney fibroblasts in CKD, but the role of different populations is still unclear. Here, we characterize a proinflammatory fibroblast population (named CXCL-iFibro), which corresponds to an early state of myofibroblast differentiation in CKD.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Chronic Kidney Disease\"); description-level mentions were not accepted. EGA study_type: Transcriptome Analysis. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Chronic_Kidney_Disease","name":"Chronic Kidney Disease","kind":"Disorder","source_path":"kb/disorders/Chronic_Kidney_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Kidney_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chronic_Kidney_Disease.html#dataset-ega-egas50000000101"}],"context_names":["Chronic Kidney Disease"],"disease_names":["Chronic Kidney Disease"],"disease_name":"Chronic Kidney Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chronic_Kidney_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Kidney_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chronic_Kidney_Disease.html#dataset-ega-egas50000000101"]},{"id":"dataset:ega:egas50000000105","accession":"ega:EGAS50000000105","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000000105","title":"Efficacy and safety of entrectinib in patients with ROS1-positive advanced/metastatic non-small cell lung cancer (NSCLC) from the Blood First Assay Screening Trial (BFAST)","alternate_titles":[],"description":"BFAST is a global, open-label, multicohort trial that evaluates the efficacy and safety of multiple therapies in patients with advanced/metastatic NSCLC and targetable alterations, identified by blood-based molecular testing. We present data from Cohort D (ROS1-positive). Patients ≥18 years old with stage IIIB/IV, ROS1-positive NSCLC detected by blood-based testing, received entrectinib 600 mg daily. At data cut-off (November 2021), 55 patients were enrolled and 54 had measurable disease.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Metastatic Non-Small Cell Lung Cancer\"); description-level mentions were not accepted. EGA study_type: Cancer Genomics. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Non-Small_Cell_Lung_Cancer","name":"Non-Small Cell Lung Cancer","kind":"Disorder","source_path":"kb/disorders/Non-Small_Cell_Lung_Cancer.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Non-Small_Cell_Lung_Cancer.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Non-Small_Cell_Lung_Cancer.html#dataset-ega-egas50000000105"}],"context_names":["Non-Small Cell Lung Cancer"],"disease_names":["Non-Small Cell Lung Cancer"],"disease_name":"Non-Small Cell Lung Cancer","same_context_model_ids":["model:kb/disorders/Non-Small_Cell_Lung_Cancer.yaml:Human orthotopic NSCLC lung organ-on-chip (Wyss Institute)"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Non-Small_Cell_Lung_Cancer.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Non-Small_Cell_Lung_Cancer.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Non-Small_Cell_Lung_Cancer.html#dataset-ega-egas50000000105"]},{"id":"dataset:ega:egas50000000159","accession":"ega:EGAS50000000159","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000000159","title":"ScRNA-seq of human kidney immune cells of patients with ANCA-associated glomerulonephritis, Lupus Nephritis against a \"healthy\" nephrectomy control","alternate_titles":[],"description":"ANCA-associated glomerulonephritis (AGN) associates with a high risk of end-stage kidney disease. The role of kidney immune cells in local inflammation remains unclear. Here, we investigate kidney immune cell diversity and function. Kidney tissue from AGN patients (n=5) and a lupus nephritis (LN) patient (n=1) were aquired during a biopsy procedure for a clinical indication. Needle-core biopsies were obtained for histopathological examination, and an additional pass was performed to retrieve kidney tissue for scRNA-seq. Healthy kidney tissue (n=1) was obtained from a kidney that was surgically removed do tue due to a (non-invasive) papillary urothelial carcinoma.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Lupus Nephritis\"); description-level mentions were not accepted. EGA study_type: RNASeq. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Lupus_Nephritis","name":"Lupus Nephritis","kind":"Disorder","source_path":"kb/disorders/Lupus_Nephritis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Lupus_Nephritis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Lupus_Nephritis.html#dataset-ega-egas50000000159"}],"context_names":["Lupus Nephritis"],"disease_names":["Lupus Nephritis"],"disease_name":"Lupus Nephritis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Lupus_Nephritis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Lupus_Nephritis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Lupus_Nephritis.html#dataset-ega-egas50000000159"]},{"id":"dataset:ega:egas50000000166","accession":"ega:EGAS50000000166","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000000166","title":"Nanopore sequencing enables allelic phasing of FLG loss-of-function variants, intragenic copy number variation and methylation status in atopic dermatitis and ichthyosis vulgaris","alternate_titles":[],"description":"Loss-of-function (LoF) variants in the FLG gene are associated with ichthyosis vulgaris (IV) and atopic dermatitis (AD). IV and AD patients with two FLG LoF variants are reported to have a more severe disease course. However, subsets of compound heterozygous patients display phenotypic heterogeneity despite a prediction of a severe phenotype from their genotype. The underlying genetic mechanism of this phenotypic variability is unknown. One possibility is that two LoF FLG variants could be located in cis (on the same allele), thus altering the predicted gene dosage.","alternate_descriptions":[],"data_types":["WGS"],"data_type_labels":["Whole genome sequencing"],"data_type_label":"Whole genome sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Atopic Dermatitis\"); description-level mentions were not accepted. EGA study_type: Whole Genome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Atopic_Dermatitis","name":"Atopic Dermatitis","kind":"Disorder","source_path":"kb/disorders/Atopic_Dermatitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Atopic_Dermatitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Atopic_Dermatitis.html#dataset-ega-egas50000000166"}],"context_names":["Atopic Dermatitis"],"disease_names":["Atopic Dermatitis"],"disease_name":"Atopic Dermatitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Atopic_Dermatitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Atopic_Dermatitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Atopic_Dermatitis.html#dataset-ega-egas50000000166"]},{"id":"dataset:ega:egas50000000192","accession":"ega:EGAS50000000192","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000000192","title":"Gene expression profiling of patient-derived fibroblasts with Maple Syrup Urine Disease (MSUD)","alternate_titles":[],"description":"Maple syrup urine disease (MSUD) is a rare inherited metabolic disorder characterized by deficient activity of the branched-chain alpha-ketoacid dehydrogenase (BCKD) complex, required to metabolize the amino acids leucine, isoleucine and valine. Despite its profound metabolic implications, the molecular alterations underlying this metabolic impairment had not yet been elucidated. We performed a comprehensive transcriptomic analysis on fibroblasts derived from a cohort of MSUD patients and unaffected controls to unravel the pathophysiology of MSUD.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Maple Syrup Urine Disease\"); description-level mentions were not accepted. EGA study_type: RNASeq. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Maple_Syrup_Urine_Disease","name":"Maple Syrup Urine Disease","kind":"Disorder","source_path":"kb/disorders/Maple_Syrup_Urine_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Maple_Syrup_Urine_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Maple_Syrup_Urine_Disease.html#dataset-ega-egas50000000192"}],"context_names":["Maple Syrup Urine Disease"],"disease_names":["Maple Syrup Urine Disease"],"disease_name":"Maple Syrup Urine Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Maple_Syrup_Urine_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Maple_Syrup_Urine_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Maple_Syrup_Urine_Disease.html#dataset-ega-egas50000000192"]},{"id":"dataset:ega:egas50000000217","accession":"ega:EGAS50000000217","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000000217","title":"Single-cell atlas of penile cancer reveals TP53 mutations as driver for an aggressive phenotype, irrespective of HPV status, and provides clues for treatment personalization","alternate_titles":[],"description":"Our aim was to identify molecular differences in the microenvironment of penile squamous cell carcinoma (PSCC) stratified by TP53 loss-of-function (TP53LOF) mutations and HPV-status. Hence, we present a first single-cell transcriptomic atlas of PSCC. Stratification based on TP53 and HPV-status uncovered differences in CSS and underlying molecular pathways. Our data indicate that TP53LOF tumors are characterized by worse biological behavior regardless of HPV-status. These findings and further research are essential for trial design in PSCC, allowing us to move away from the current one-size-fits-all approach.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Penile Cancer\"); description-level mentions were not accepted. EGA study_type: Transcriptome Analysis. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Penile_Cancer","name":"Penile Cancer","kind":"Disorder","source_path":"kb/disorders/Penile_Cancer.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Penile_Cancer.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Penile_Cancer.html#dataset-ega-egas50000000217"}],"context_names":["Penile Cancer"],"disease_names":["Penile Cancer"],"disease_name":"Penile Cancer","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Penile_Cancer.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Penile_Cancer.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Penile_Cancer.html#dataset-ega-egas50000000217"]},{"id":"dataset:ega:egas50000000226","accession":"ega:EGAS50000000226","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000000226","title":"Combined single-cell transcriptomics and T-cell receptor sequencing reveal heterogeneity of mycosis fungoides between and within patients and identify a CD4+ cytotoxic subtype","alternate_titles":[],"description":"Comprehensive analysis of the malignant cells present in the skin lesions of Mycosis fungoides, the most common subtype of cutaneous T-cell lymphoma, is complicated by the fact that malignant from reactive T cells are challenging to distinguish with certainty. To this end, combined single-cell RNA and TCR sequencing allows unambiguous identification of MF cells, thereby revealing a marked heterogeneity between and within patients with unexpected functional phenotypes.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Mycosis Fungoides\"); description-level mentions were not accepted. EGA study_type: RNASeq. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Mycosis_Fungoides","name":"Mycosis Fungoides","kind":"Disorder","source_path":"kb/disorders/Mycosis_Fungoides.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mycosis_Fungoides.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Mycosis_Fungoides.html#dataset-ega-egas50000000226"}],"context_names":["Mycosis Fungoides"],"disease_names":["Mycosis Fungoides"],"disease_name":"Mycosis Fungoides","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Mycosis_Fungoides.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mycosis_Fungoides.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Mycosis_Fungoides.html#dataset-ega-egas50000000226"]},{"id":"dataset:ega:egas50000000298","accession":"ega:EGAS50000000298","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000000298","title":"A CCG expansion in ABCD3 causes oculopharyngodistal myopathy in individuals of European ancestry","alternate_titles":[],"description":"In this study we describe the identification of CCG expansions in ABCD3 in affected individuals across eight unrelated OPDM families of European ancestry. In two large Australian OPDM families, using a combination of linkage studies, short-read WGS and targeted ONT sequencing, we identified CCG expansions in the 5’UTR of ABCD3. Independently, the ABCD3 CCG expansion was identified through the 100,000 Genomics England Genome Project in three individuals from two unrelated UK families diagnosed with OPDM.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Oculopharyngodistal Myopathy\"); description-level mentions were not accepted. EGA study_type: RNASeq. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Oculopharyngodistal_Myopathy","name":"Oculopharyngodistal Myopathy","kind":"Disorder","source_path":"kb/disorders/Oculopharyngodistal_Myopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Oculopharyngodistal_Myopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Oculopharyngodistal_Myopathy.html#dataset-ega-egas50000000298"}],"context_names":["Oculopharyngodistal Myopathy"],"disease_names":["Oculopharyngodistal Myopathy"],"disease_name":"Oculopharyngodistal Myopathy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Oculopharyngodistal_Myopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Oculopharyngodistal_Myopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Oculopharyngodistal_Myopathy.html#dataset-ega-egas50000000298"]},{"id":"dataset:ega:egas50000000310","accession":"ega:EGAS50000000310","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000000310","title":"Cell type mapping of inflammatory muscle diseases highlights selective myofiber vulnerability in inclusion body myositis","alternate_titles":[],"description":"Inclusion body myositis (IBM) is the most prevalent inflammatory muscle disease in older adults with no effective therapy available. In contrast to other inflammatory myopathies like subacute immune-mediated necrotizing myopathy (IMNM), IBM follows a chronic disease course with both inflammatory and degenerative features of pathology. Moreover, causal factors and molecular drivers of IBM progression are largely unknown. Therefore, we paired single-nucleus RNA sequencing with spatial transcriptomics from patient muscle biopsies to map cell type-specific drivers underlying IBM pathogenesis compared to IMNM muscles and non-inflammatory skeletal muscle samples.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Inclusion Body Myositis\"); description-level mentions were not accepted. EGA study_type: RNASeq. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Inclusion_Body_Myositis","name":"Inclusion Body Myositis","kind":"Disorder","source_path":"kb/disorders/Inclusion_Body_Myositis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Inclusion_Body_Myositis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Inclusion_Body_Myositis.html#dataset-ega-egas50000000310"}],"context_names":["Inclusion Body Myositis"],"disease_names":["Inclusion Body Myositis"],"disease_name":"Inclusion Body Myositis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Inclusion_Body_Myositis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Inclusion_Body_Myositis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Inclusion_Body_Myositis.html#dataset-ega-egas50000000310"]},{"id":"dataset:ega:egas50000000335","accession":"ega:EGAS50000000335","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000000335","title":"single cell data from HPV-positive head and neck cancer patients receiving induction CTLA-4 and PD-1 immune checkpoint blockade","alternate_titles":[],"description":"Baseline and on-treatment tumor samples from human papillomavirus-positive oropharynx cancer patients receiving anti-CTLA-4 and anti-PD-1 immune checkpoint blockade were analyzed by single-cell RNA and TCR sequencing.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"HPV-Positive Head and Neck Cancer\"); description-level mentions were not accepted. EGA study_type: Transcriptome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:HPV_Positive_Head_and_Neck_Cancer","name":"HPV-Positive Head and Neck Cancer","kind":"Disorder","source_path":"kb/disorders/HPV_Positive_Head_and_Neck_Cancer.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/HPV_Positive_Head_and_Neck_Cancer.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/HPV-Positive_Head_and_Neck_Cancer.html#dataset-ega-egas50000000335"}],"context_names":["HPV-Positive Head and Neck Cancer"],"disease_names":["HPV-Positive Head and Neck Cancer"],"disease_name":"HPV-Positive Head and Neck Cancer","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/HPV_Positive_Head_and_Neck_Cancer.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/HPV_Positive_Head_and_Neck_Cancer.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/HPV-Positive_Head_and_Neck_Cancer.html#dataset-ega-egas50000000335"]},{"id":"dataset:ega:egas50000000367","accession":"ega:EGAS50000000367","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000000367","title":"Targeting Heterochromatin Eliminates Malignant Stem Cells in Chronic Myelomonocytic Leukemia Through Reactivation of Retroelements and Innate Immune pathways","alternate_titles":[],"description":"Hematopoietic stem cell (HSC) aging involves heterochromatin reorganization. These repressive marks together with DNA methylation are essential for suppressing transposable elements (TEs). In this study we analyze heterochromatin and transcriptomic changes occurring at genes and TEs in HSCs from chronic myelomonocytic leukemia, a severe myeloid malignancy affecting the elderly, compared to age-matched cells, and in the presence or absence of a combination of epidrugs.","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Chronic Myelomonocytic Leukemia\"); description-level mentions were not accepted. EGA study_type: Epigenetics. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Chronic_Myelomonocytic_Leukemia","name":"Chronic Myelomonocytic Leukemia","kind":"Disorder","source_path":"kb/disorders/Chronic_Myelomonocytic_Leukemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Myelomonocytic_Leukemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chronic_Myelomonocytic_Leukemia.html#dataset-ega-egas50000000367"}],"context_names":["Chronic Myelomonocytic Leukemia"],"disease_names":["Chronic Myelomonocytic Leukemia"],"disease_name":"Chronic Myelomonocytic Leukemia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chronic_Myelomonocytic_Leukemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Myelomonocytic_Leukemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chronic_Myelomonocytic_Leukemia.html#dataset-ega-egas50000000367"]},{"id":"dataset:ega:egas50000000368","accession":"ega:EGAS50000000368","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000000368","title":"COVID-19 progression and convalescence in common variable immunodeficiency patients","alternate_titles":[],"description":"Longitudinal analysis of single-cell RNAseq datasets of PBMCs from COVID-19 CVID patients and controls.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Common Variable Immunodeficiency\"); description-level mentions were not accepted. EGA study_type: Transcriptome Analysis. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Common_Variable_Immunodeficiency","name":"Common Variable Immunodeficiency","kind":"Disorder","source_path":"kb/disorders/Common_Variable_Immunodeficiency.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Common_Variable_Immunodeficiency.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Common_Variable_Immunodeficiency.html#dataset-ega-egas50000000368"}],"context_names":["Common Variable Immunodeficiency"],"disease_names":["Common Variable Immunodeficiency"],"disease_name":"Common Variable Immunodeficiency","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Common_Variable_Immunodeficiency.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Common_Variable_Immunodeficiency.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Common_Variable_Immunodeficiency.html#dataset-ega-egas50000000368"]},{"id":"dataset:ega:egas50000000381","accession":"ega:EGAS50000000381","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000000381","title":"Epigenetic landscape reorganization and reactivation of embryonic development genes are associated with malignancy in IDH-mutant astrocytoma","alternate_titles":[],"description":"Accurate grading of IDH-mutant gliomas is crucial for determining patient prognosis and guiding treatment decisions. 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Using this data, we sought to identify molecular markers linked to increased malignancy in IDH-mutant astrocytomas to establish objective grading criteria.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"IDH-Mutant Astrocytoma\"); description-level mentions were not accepted. EGA study_type: RNASeq. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:IDH_Mutant_Astrocytoma","name":"IDH-Mutant Astrocytoma","kind":"Disorder","source_path":"kb/disorders/IDH_Mutant_Astrocytoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/IDH_Mutant_Astrocytoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/IDH-Mutant_Astrocytoma.html#dataset-ega-egas50000000381"}],"context_names":["IDH-Mutant Astrocytoma"],"disease_names":["IDH-Mutant Astrocytoma"],"disease_name":"IDH-Mutant Astrocytoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/IDH_Mutant_Astrocytoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/IDH_Mutant_Astrocytoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/IDH-Mutant_Astrocytoma.html#dataset-ega-egas50000000381"]},{"id":"dataset:ega:egas50000000502","accession":"ega:EGAS50000000502","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000000502","title":"3D tissue engineered human skeletal muscle modelling Facioscapulohumeral Muscular Dystrophy","alternate_titles":[],"description":"acioscapulohumeral muscular dystrophy (FSHD) is caused by sporadic misexpression of the transcription factor double homeobox 4 (DUX4) in skeletal muscles. So far, monolayer cultures and animal models have been used to study the FSHD disease mechanism and for FSHD therapy development, but these models do not fully recapitulate the disease and there is a lack of knowledge on how DUX4 misexpression leads to skeletal muscle dysfunction. To overcome these barriers, we have developed a 3D tissue engineered skeletal muscle (3D-TESM) model by generating genetically matched myogenic progenitors (MPs) from human induced pluripotent stem cells of three mosaic FSHD patients.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Facioscapulohumeral Muscular Dystrophy\"); description-level mentions were not accepted. EGA study_type: RNASeq. Controlled access -- data require a Data Access Agreement. 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EGA study_type: Whole Genome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:22q11.2_Deletion_Syndrome","name":"22q11.2 Deletion Syndrome","kind":"Disorder","source_path":"kb/disorders/22q11.2_Deletion_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/22q11.2_Deletion_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/22q11.2_Deletion_Syndrome.html#dataset-ega-egas50000000601"}],"context_names":["22q11.2 Deletion Syndrome"],"disease_names":["22q11.2 Deletion Syndrome"],"disease_name":"22q11.2 Deletion Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/22q11.2_Deletion_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/22q11.2_Deletion_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/22q11.2_Deletion_Syndrome.html#dataset-ega-egas50000000601"]},{"id":"dataset:ega:egas50000000612","accession":"ega:EGAS50000000612","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000000612","title":"Single cell transcriptome analysis of pediatric acute megakaryoblastic leukemia","alternate_titles":[],"description":"Pediatric acute megakaryoblastic leukemia presenting fusion oncogene is generally associated with a poor prognosis. 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EGA study_type: RNASeq. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Acute_Megakaryoblastic_Leukemia","name":"Acute Megakaryoblastic Leukemia","kind":"Disorder","source_path":"kb/disorders/Acute_Megakaryoblastic_Leukemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Acute_Megakaryoblastic_Leukemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Acute_Megakaryoblastic_Leukemia.html#dataset-ega-egas50000000612"}],"context_names":["Acute Megakaryoblastic Leukemia"],"disease_names":["Acute Megakaryoblastic Leukemia"],"disease_name":"Acute Megakaryoblastic Leukemia","same_context_model_ids":["model:kb/disorders/Acute_Megakaryoblastic_Leukemia.yaml:CBFA2T3-GLIS2 Cord-Blood HSPC Endothelial Coculture","model:kb/disorders/Acute_Megakaryoblastic_Leukemia.yaml:NUP98-KDM5A Cord-Blood HSPC Model","model:kb/disorders/Acute_Megakaryoblastic_Leukemia.yaml:Trisomy-21 GATA1/STAG2 Double-Mutant iPSC Model"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Acute_Megakaryoblastic_Leukemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Acute_Megakaryoblastic_Leukemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Acute_Megakaryoblastic_Leukemia.html#dataset-ega-egas50000000612"]},{"id":"dataset:ega:egas50000000646","accession":"ega:EGAS50000000646","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000000646","title":"Host factors dictate gut microbiome alterations in chronic kidney disease more strongly than to kidney function","alternate_titles":[],"description":"Despite recent progress, microbial markers in Chronic Kidney Disease (CKD) remain inconclusive. We combined quantitative faecal metagenomics (N=130 CKD cohort) and cross-study biomarker comparisons (Ntotal=4420) to study microbiome associations with glomerular filtration rate (eGFR; kidney function) and 4-year CKD progression. Transit time (TT) and medications primarily explained microbiome variation, trumping eGFR-related effects.","alternate_descriptions":[],"data_types":["WGS"],"data_type_labels":["Whole genome sequencing"],"data_type_label":"Whole genome sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Chronic Kidney Disease\"); description-level mentions were not accepted. EGA study_type: Metagenomics. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Chronic_Kidney_Disease","name":"Chronic Kidney Disease","kind":"Disorder","source_path":"kb/disorders/Chronic_Kidney_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Kidney_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chronic_Kidney_Disease.html#dataset-ega-egas50000000646"}],"context_names":["Chronic Kidney Disease"],"disease_names":["Chronic Kidney Disease"],"disease_name":"Chronic Kidney Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chronic_Kidney_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Kidney_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chronic_Kidney_Disease.html#dataset-ega-egas50000000646"]},{"id":"dataset:ega:egas50000000647","accession":"ega:EGAS50000000647","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000000647","title":"Transcriptomic profiling of fragile X syndrome unmethylated full mutation carriers","alternate_titles":[],"description":"Total RNA sequencing of fibroblasts from two unrelated FMR1 unmethylated full mutation carriers, a fragile X patient and a control individual. 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This study aims to compare the transcriptomes of these four individuals in order to elucidate the mechanism behind the methylation a the FMR1 CGG repeat expansion that causes Fragile X syndrome.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Fragile X Syndrome\"); description-level mentions were not accepted. EGA study_type: RNASeq. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Fragile_X_Syndrome","name":"Fragile X Syndrome","kind":"Disorder","source_path":"kb/disorders/Fragile_X_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fragile_X_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Fragile_X_Syndrome.html#dataset-ega-egas50000000647"}],"context_names":["Fragile X Syndrome"],"disease_names":["Fragile X Syndrome"],"disease_name":"Fragile X Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Fragile_X_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fragile_X_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Fragile_X_Syndrome.html#dataset-ega-egas50000000647"]},{"id":"dataset:ega:egas50000000648","accession":"ega:EGAS50000000648","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000000648","title":"Genomic profiling of fragile X syndrome unmethylated full mutation carriers","alternate_titles":[],"description":"Whole genome sequencing of two unrelated FMR1 unmethylated full mutation carriers. The existence of rare, unmethylated full mutation carriers who carry the mutation that causes fragile X syndrome but do not gain methylation at the locus offers a rare opportunity to study the mechanisms underlying fragile X syndrome. 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EGA study_type: Whole Genome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Fragile_X_Syndrome","name":"Fragile X Syndrome","kind":"Disorder","source_path":"kb/disorders/Fragile_X_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fragile_X_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Fragile_X_Syndrome.html#dataset-ega-egas50000000648"}],"context_names":["Fragile X Syndrome"],"disease_names":["Fragile X Syndrome"],"disease_name":"Fragile X Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Fragile_X_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fragile_X_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Fragile_X_Syndrome.html#dataset-ega-egas50000000648"]},{"id":"dataset:ega:egas50000000653","accession":"ega:EGAS50000000653","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000000653","title":"Single-cell spatiotranscriptomic dissection of ex vivo human heart right atrial appendage and pericardial fluid in ischemic heart disease and heart failure","alternate_titles":[],"description":"We use cardiac and pericardial fluid biopsies collected during open-heart surgery in control, ischemic heart disease, heart failure, and myocardial infarction context. For each sample, single-nuclei RNA sequencing experiment is performed. We also perform spatial transcriptomics on the heart samples. We annotate the cells in major cell types, in addition to subtypes annotation of vascular and immune cells. The disease annotation enables us to reveal substantial differences in gene expression at the cell subpopulation levels. Our results demonstrate the importance of high-resolution cellular type/state mapping in the elucidation of human cardiovascular disease pathogenesis.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:38776872"],"publication_contexts":[{"context_id":"disorder:Heart_Failure","publication":"PMID:38776872"}],"publication":"PMID:38776872","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38776872","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Heart Failure\"); description-level mentions were not accepted. EGA study_type: Transcriptome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Heart_Failure","name":"Heart Failure","kind":"Disorder","source_path":"kb/disorders/Heart_Failure.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Heart_Failure.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Heart_Failure.html#dataset-ega-egas50000000653"}],"context_names":["Heart Failure"],"disease_names":["Heart Failure"],"disease_name":"Heart Failure","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Heart_Failure.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Heart_Failure.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Heart_Failure.html#dataset-ega-egas50000000653"]},{"id":"dataset:ega:egas50000000714","accession":"ega:EGAS50000000714","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000000714","title":"Molecular correlates for HPV-negative head and neck cancer engraftment prognosticate patient outcomes","alternate_titles":[],"description":"Head and neck squamous cell carcinoma (HNSCC) tumors were sampled from 88 patients. Samples were implanted subcutaenously into the flank of NOD/SCID/IL2R-/- mice. Mice were then monitored weekly for tumor growth and the time of initial palpation was recorded. Mice were euthanized when tumors reached 15 mm in diameter or after 6 months. If no tumor formed by 6 months, the patient tumor was defined as Non-engrafter (N). RNA-seq was performed on all primary tumor samples and successfully engrafted patient-derived xenograft (PDX) samples.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"HPV-Negative Head and Neck Cancer\"); description-level mentions were not accepted. EGA study_type: RNASeq. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:HPV_Negative_Head_and_Neck_Cancer","name":"HPV-Negative Head and Neck Cancer","kind":"Disorder","source_path":"kb/disorders/HPV_Negative_Head_and_Neck_Cancer.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/HPV_Negative_Head_and_Neck_Cancer.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/HPV-Negative_Head_and_Neck_Cancer.html#dataset-ega-egas50000000714"}],"context_names":["HPV-Negative Head and Neck Cancer"],"disease_names":["HPV-Negative Head and Neck Cancer"],"disease_name":"HPV-Negative Head and Neck Cancer","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/HPV_Negative_Head_and_Neck_Cancer.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/HPV_Negative_Head_and_Neck_Cancer.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/HPV-Negative_Head_and_Neck_Cancer.html#dataset-ega-egas50000000714"]},{"id":"dataset:ega:egas50000000735","accession":"ega:EGAS50000000735","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000000735","title":"Single-Cell Profiling of the Human Endometrium in Polycystic Ovary Syndrome: Uncovering Disease Signatures and Treatment Responses","alternate_titles":[],"description":"We generated the first single-nuclei map of human endometrial biopsies from women with and without PCOS to identify cell-type-specific disease signatures, compositional variations, and transcriptomic reversibility after a 16-week intervention with metformin or lifestyle. Single nuclei were extracted from 27 frozen endometrial biopsies for snRNA-seq using the 10X Genomics protocol.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Polycystic Ovary Syndrome\"); description-level mentions were not accepted. EGA study_type: Transcriptome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Polycystic_Ovary_Syndrome","name":"Polycystic Ovary Syndrome","kind":"Disorder","source_path":"kb/disorders/Polycystic_Ovary_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Polycystic_Ovary_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Polycystic_Ovary_Syndrome.html#dataset-ega-egas50000000735"}],"context_names":["Polycystic Ovary Syndrome"],"disease_names":["Polycystic Ovary Syndrome"],"disease_name":"Polycystic Ovary Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Polycystic_Ovary_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Polycystic_Ovary_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Polycystic_Ovary_Syndrome.html#dataset-ega-egas50000000735"]},{"id":"dataset:ega:egas50000000808","accession":"ega:EGAS50000000808","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000000808","title":"Impact of Glycolysis Inhibition on the Epigenome of Synovial Fluid T Cells in Juvenile Idiopathic Arthritis","alternate_titles":[],"description":"Juvenile Idiopathic Arthritis (JIA) encompasses a group of childhood-onset autoimmune conditions characterized by joint inflammation and mononuclear cell infiltration, especially of activated CD4+ memory/effector T (Tmem/Teff) cells in synovial fluid (SF). JIA CD4+ T cells exhibit a distinct inflammation-associated epigenomic profile, though the underlying molecular mechanisms remain unclear. This study investigates the role of glycolysis in shaping the epigenomic landscape of JIA SF CD4+ T cells, with a focus on H3K27ac histone modifications.","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Juvenile Idiopathic Arthritis\"); description-level mentions were not accepted. EGA study_type: Epigenetics. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Juvenile_Idiopathic_Arthritis","name":"Juvenile Idiopathic Arthritis","kind":"Disorder","source_path":"kb/disorders/Juvenile_Idiopathic_Arthritis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Juvenile_Idiopathic_Arthritis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Juvenile_Idiopathic_Arthritis.html#dataset-ega-egas50000000808"}],"context_names":["Juvenile Idiopathic Arthritis"],"disease_names":["Juvenile Idiopathic Arthritis"],"disease_name":"Juvenile Idiopathic Arthritis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Juvenile_Idiopathic_Arthritis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Juvenile_Idiopathic_Arthritis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Juvenile_Idiopathic_Arthritis.html#dataset-ega-egas50000000808"]},{"id":"dataset:ega:egas50000000810","accession":"ega:EGAS50000000810","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000000810","title":"Integrated Transcriptomic and Regulatory RNA Profiling Reflects Complex Pathophysiology and Uncovers a Conserved Gene Signature in End Stage Heart Failure RNA-Seq data","alternate_titles":[],"description":"Heart failure (HF) is a complex syndrome. Despite availability of multiple treatment options, the mortality remains high and the quality of life poor. Better understanding of the underlying pathophysiological processes can lead to development of novel therapies. Multiple comparative transcriptomics studies, which revealed gene level changes in the key pathophysiological pathways in failing hearts, point towards heterogeneity from interplay of disease stage, etiologies and ethnicity. Transcriptomic characterization of HF in patients from different ethnicities can potentially help in understanding the heterogeneity imparted by various factors and the core elements in heart failure.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Heart Failure\"); description-level mentions were not accepted. EGA study_type: RNASeq. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Heart_Failure","name":"Heart Failure","kind":"Disorder","source_path":"kb/disorders/Heart_Failure.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Heart_Failure.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Heart_Failure.html#dataset-ega-egas50000000810"}],"context_names":["Heart Failure"],"disease_names":["Heart Failure"],"disease_name":"Heart Failure","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Heart_Failure.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Heart_Failure.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Heart_Failure.html#dataset-ega-egas50000000810"]},{"id":"dataset:ega:egas50000000811","accession":"ega:EGAS50000000811","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000000811","title":"Measles oncolytic virus as an immunotherapy for recurrent/refractory pediatric medulloblastoma and atypical teratoid rhabdoid tumor","alternate_titles":[],"description":"Pediatric recurrent medulloblastoma (MB) and atypical teratoid rhabdoid tumor (ATRT) are largely incurable and warrant novel therapies. We investigated a) the safety of a measles virus variant, MV-NIS, in a pediatric phase 1 study and b) the mechanisms of MV-NIS and potential benefit of combination with immune checkpoint inhibition (ICI). Pediatric patients with recurrent MB or ATRT were treated with intratumoral injections for local recurrence or via lumbar puncture for disseminated recurrence. We evaluated local immune responses to MV-NIS with and without ICI via single-cell and bulk RNA sequencing in an intracranial, immunocompetent, syngeneic murine model.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"atypical teratoid rhabdoid tumor\"); description-level mentions were not accepted. EGA study_type: Transcriptome Analysis. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Atypical_Teratoid_Rhabdoid_Tumor","name":"Atypical Teratoid/Rhabdoid Tumor","kind":"Disorder","source_path":"kb/disorders/Atypical_Teratoid_Rhabdoid_Tumor.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Atypical_Teratoid_Rhabdoid_Tumor.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Atypical_Teratoid_Rhabdoid_Tumor.html#dataset-ega-egas50000000811"}],"context_names":["Atypical Teratoid/Rhabdoid Tumor"],"disease_names":["Atypical Teratoid/Rhabdoid Tumor"],"disease_name":"Atypical Teratoid/Rhabdoid Tumor","same_context_model_ids":["model:kb/disorders/Atypical_Teratoid_Rhabdoid_Tumor.yaml:Patient-derived AT/RT tumoroids"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Atypical_Teratoid_Rhabdoid_Tumor.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Atypical_Teratoid_Rhabdoid_Tumor.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Atypical_Teratoid_Rhabdoid_Tumor.html#dataset-ega-egas50000000811"]},{"id":"dataset:ega:egas50000000904","accession":"ega:EGAS50000000904","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000000904","title":"Deciphering the complex clonal heterogeneity of polycythemia vera and the response to interferon alpha","alternate_titles":[],"description":"We integrated colony formation and differentiation assays with single-cell RNA sequencing and single-cell genotyping in PV patient-derived cells vs. healthy controls to dissect how IFNa targets diseased clones during erythroid differentiation. Our findings indicate that PV-derived clones either undergo apoptosis or pass through their typical differentiation cycle, contributing to the long-term exhaustion of mutant cells in the bone marrow. The pivotal roles of ribosomal genes and clonal prerequisites in the therapeutic mechanism of IFNa are underscored by our study.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Polycythemia Vera\"); description-level mentions were not accepted. EGA study_type: RNASeq. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Polycythemia_Vera","name":"Polycythemia Vera","kind":"Disorder","source_path":"kb/disorders/Polycythemia_Vera.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Polycythemia_Vera.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Polycythemia_Vera.html#dataset-ega-egas50000000904"}],"context_names":["Polycythemia Vera"],"disease_names":["Polycythemia Vera"],"disease_name":"Polycythemia Vera","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Polycythemia_Vera.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Polycythemia_Vera.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Polycythemia_Vera.html#dataset-ega-egas50000000904"]},{"id":"dataset:ega:egas50000000913","accession":"ega:EGAS50000000913","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000000913","title":"Multi-omic analyses from a randomized phase II study of epigenetic priming followed by nivolumab in previously treated metastatic non-small cell lung cancer","alternate_titles":[],"description":"Emergence of resistance to immune checkpoint blockade (ICB) mandates the development of strategies for ICB sensitization. We aimed to understand the effects of epigenetic priming in re-shaping the tumor microenvironment, together with molecular drivers of therapeutic response of epigenetic therapy followed by ICB in non-small cell lung cancer (NSCLC; NCT01928576). This was done through a multi-omic approach encompassing both genomic and transcriptomic analyses. Findings suggest that epigenetic therapy may reshape the tumor microenvironment towards a more inflamed phenotype and prime responses to immunotherapy.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Metastatic Non-Small Cell Lung Cancer\"); description-level mentions were not accepted. EGA study_type: Cancer Genomics. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Non-Small_Cell_Lung_Cancer","name":"Non-Small Cell Lung Cancer","kind":"Disorder","source_path":"kb/disorders/Non-Small_Cell_Lung_Cancer.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Non-Small_Cell_Lung_Cancer.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Non-Small_Cell_Lung_Cancer.html#dataset-ega-egas50000000913"}],"context_names":["Non-Small Cell Lung Cancer"],"disease_names":["Non-Small Cell Lung Cancer"],"disease_name":"Non-Small Cell Lung Cancer","same_context_model_ids":["model:kb/disorders/Non-Small_Cell_Lung_Cancer.yaml:Human orthotopic NSCLC lung organ-on-chip (Wyss Institute)"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Non-Small_Cell_Lung_Cancer.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Non-Small_Cell_Lung_Cancer.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Non-Small_Cell_Lung_Cancer.html#dataset-ega-egas50000000913"]},{"id":"dataset:ega:egas50000000973","accession":"ega:EGAS50000000973","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000000973","title":"Multi-omics bulk and single-cell profiling of epithelioid sarcoma","alternate_titles":[],"description":"Epithelioid sarcoma (EpS) is an aggressive sarcoma, characterized by the loss of SMARCB1 expression. EpS is traditionally classified as distal or proximal according to clinicopathological features, but its molecular characteristics remain largely unknown. To establish an EpS molecular classification and uncover determinants of inter- and intra-patient heterogeneity in EpS, we used multi-omics profiling and integrated the genomic, transcriptional and methylome landscapes with single-cell RNA sequencing on fresh samples as well as spatial transcriptomics. We identified two molecular subtypes of EpS: “distal-like” and “proximal-like”, which were distinct from the histological subtypes.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Epithelioid Sarcoma\"); description-level mentions were not accepted. EGA study_type: Cancer Genomics. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Epithelioid_Sarcoma","name":"Epithelioid Sarcoma","kind":"Disorder","source_path":"kb/disorders/Epithelioid_Sarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Epithelioid_Sarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Epithelioid_Sarcoma.html#dataset-ega-egas50000000973"}],"context_names":["Epithelioid Sarcoma"],"disease_names":["Epithelioid Sarcoma"],"disease_name":"Epithelioid Sarcoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Epithelioid_Sarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Epithelioid_Sarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Epithelioid_Sarcoma.html#dataset-ega-egas50000000973"]},{"id":"dataset:ega:egas50000000988","accession":"ega:EGAS50000000988","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000000988","title":"Transcriptome analysis of 32 pheochromocytoma and paraganglioma samples","alternate_titles":[],"description":"Pheochromocytomas and sympathetic paragangliomas (PPGL) are rare neuroendocrine tumors derived from chromaffin tissue of the adrenal medulla and sympathetic paraganglia, respectively. There is at the moment a lack of accurate biomarkers to predict the biologic behavior of a PPGL. The aim of this study was to investigate the biological behavior of localized and metastatic PPGL by comparing the genomic and transcriptomic landscapes of localized and metastatic PPGL, including PPGL samples with a non-metastatic phenotype at initial diagnosis that developed metachronous metastases during follow-up.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Pheochromocytoma and Paraganglioma\"); description-level mentions were not accepted. EGA study_type: RNASeq. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Pheochromocytoma_Paraganglioma","name":"Pheochromocytoma and Paraganglioma","kind":"Disorder","source_path":"kb/disorders/Pheochromocytoma_Paraganglioma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pheochromocytoma_Paraganglioma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pheochromocytoma_and_Paraganglioma.html#dataset-ega-egas50000000988"}],"context_names":["Pheochromocytoma and Paraganglioma"],"disease_names":["Pheochromocytoma and Paraganglioma"],"disease_name":"Pheochromocytoma and Paraganglioma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Pheochromocytoma_Paraganglioma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pheochromocytoma_Paraganglioma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Pheochromocytoma_and_Paraganglioma.html#dataset-ega-egas50000000988"]},{"id":"dataset:ega:egas50000000995","accession":"ega:EGAS50000000995","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000000995","title":"CLUSTER RNAseq Study of Juvenile Idiopathic Arthritis patients in methotrexate cohort","alternate_titles":[],"description":"CLUSTER aims to discover novel disease mechanisms and biomarkers in children suffering from Juvenile idiopathic arthritis (JIA). Currently, little is known about the pathological disease mechanisms of JIA and there are no validated tools capable of predicting response or non-response to treatment. The study aims to identify biomarkers for treatment response using RNAseq technology. The samples used in this study comes from blood samples that were collected prior to patients receiving methotrexate treatment (naive). These samples were then processed for PBMC isolation followed by sorting cells into 4 different immune cell types. All of these samples were then sequenced by NovaSeq6000.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40681434"],"publication_contexts":[{"context_id":"disorder:Juvenile_Idiopathic_Arthritis","publication":"PMID:40681434"}],"publication":"PMID:40681434","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40681434","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Juvenile Idiopathic Arthritis\"); description-level mentions were not accepted. EGA study_type: RNASeq. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Juvenile_Idiopathic_Arthritis","name":"Juvenile Idiopathic Arthritis","kind":"Disorder","source_path":"kb/disorders/Juvenile_Idiopathic_Arthritis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Juvenile_Idiopathic_Arthritis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Juvenile_Idiopathic_Arthritis.html#dataset-ega-egas50000000995"}],"context_names":["Juvenile Idiopathic Arthritis"],"disease_names":["Juvenile Idiopathic Arthritis"],"disease_name":"Juvenile Idiopathic Arthritis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Juvenile_Idiopathic_Arthritis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Juvenile_Idiopathic_Arthritis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Juvenile_Idiopathic_Arthritis.html#dataset-ega-egas50000000995"]},{"id":"dataset:ega:egas50000001178","accession":"ega:EGAS50000001178","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000001178","title":"Exome Sequencing of familial and sporadic Meniere disease patients","alternate_titles":[],"description":"This study aims to characterize the genetic architecture of spanish patients diagnosed with Meniere disease (MD), focusing on both familial (FMD) and sporadic (SMD) forms, by analyzing coding variants. Whole-exome sequencing was performed on these patients, and variants were called and annotated using the nf-core/sarek bioinformatics pipeline, including alignment to the GRCh38 reference genome. The resulting data provide a curated resource for investigating the potential genetic contribution to the pathophysiology of MD. All data will be made available for reuse under controlled access.","alternate_descriptions":[],"data_types":["WES"],"data_type_labels":["Whole exome sequencing"],"data_type_label":"Whole exome sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Meniere disease\"); description-level mentions were not accepted. EGA study_type: Exome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Menieres_Disease","name":"Meniere's Disease","kind":"Disorder","source_path":"kb/disorders/Menieres_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Menieres_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Meniere's_Disease.html#dataset-ega-egas50000001178"}],"context_names":["Meniere's Disease"],"disease_names":["Meniere's Disease"],"disease_name":"Meniere's Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Menieres_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Menieres_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Meniere's_Disease.html#dataset-ega-egas50000001178"]},{"id":"dataset:ega:egas50000001214","accession":"ega:EGAS50000001214","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000001214","title":"Analysis of transcriptomic landscape of iPSC-derived neurons in Williams Syndrome","alternate_titles":[],"description":"To analyse the transcriptomic changes in iPSC-derived neuronal cells derived from individuals with Williams syndrome vs. controls at different stages of neuronal maturation. This was done to better understand how the deletion responsible for WS alters neuronal development thereby resulting in the characteristic WS phenotype","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Williams Syndrome\"); description-level mentions were not accepted. EGA study_type: RNASeq. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Williams_Syndrome","name":"Williams Syndrome","kind":"Disorder","source_path":"kb/disorders/Williams_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Williams_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Williams_Syndrome.html#dataset-ega-egas50000001214"}],"context_names":["Williams Syndrome"],"disease_names":["Williams Syndrome"],"disease_name":"Williams Syndrome","same_context_model_ids":["model:kb/disorders/Williams_Syndrome.yaml:Patient-derived and isogenic 7q11.23 dosage-series induced neurons","model:kb/disorders/Williams_Syndrome.yaml:Williams syndrome patient-derived neural progenitors and cortical neurons"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Williams_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Williams_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Williams_Syndrome.html#dataset-ega-egas50000001214"]},{"id":"dataset:ega:egas50000001258","accession":"ega:EGAS50000001258","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000001258","title":"Genetic and Microenvironmental Analysis of Peripheral T-cell Lymphoma","alternate_titles":[],"description":"This study enrolled 129 patients diagnosed with PTCL, comprising 94 cases of nTFHL and 35 cases of PTCL-NOS. Whole exome sequencing (WES) and RNA sequencing (RNA-seq) were performed using DNA and RNA of sufficient quality extracted from their tumor specimens. WES was conducted for all 129 cases, while RNA-seq was performed on 57 tumor samples.","alternate_descriptions":[],"data_types":["WES"],"data_type_labels":["Whole exome sequencing"],"data_type_label":"Whole exome sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Peripheral T-Cell Lymphoma\"); description-level mentions were not accepted. EGA study_type: Exome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Peripheral_T_Cell_Lymphoma","name":"Peripheral T-Cell Lymphoma","kind":"Disorder","source_path":"kb/disorders/Peripheral_T_Cell_Lymphoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Peripheral_T_Cell_Lymphoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Peripheral_T-Cell_Lymphoma.html#dataset-ega-egas50000001258"}],"context_names":["Peripheral T-Cell Lymphoma"],"disease_names":["Peripheral T-Cell Lymphoma"],"disease_name":"Peripheral T-Cell Lymphoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Peripheral_T_Cell_Lymphoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Peripheral_T_Cell_Lymphoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Peripheral_T-Cell_Lymphoma.html#dataset-ega-egas50000001258"]},{"id":"dataset:ega:egas50000001275","accession":"ega:EGAS50000001275","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000001275","title":"Heritable pulmonary arterial hypertension - new genetic findings and environmental triggers","alternate_titles":[],"description":"Whole exome sequencing data were analysed for a total of 13 family members of five heritable pulmonary arterial hypertension (HPAH) families to identify a disease causing variant. In a first step, variants only present in affected family members and absent in healthy relatives of the respective family were selected. Subsequently, due to incomplete penetrance of genes in PAH, the analysis was extended to variants present both in affected and healthy individuals. Heterozygous variants were primarily investigated followed by homozygous, compound heterozygous, and bi-allelic variants of interest. This study led to the identification of rare deleterious variants in three out of five families.","alternate_descriptions":[],"data_types":["WES"],"data_type_labels":["Whole exome sequencing"],"data_type_label":"Whole exome sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Heritable Pulmonary Arterial Hypertension\"); description-level mentions were not accepted. EGA study_type: Exome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Heritable_Pulmonary_Arterial_Hypertension","name":"Heritable Pulmonary Arterial Hypertension","kind":"Disorder","source_path":"kb/disorders/Heritable_Pulmonary_Arterial_Hypertension.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Heritable_Pulmonary_Arterial_Hypertension.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Heritable_Pulmonary_Arterial_Hypertension.html#dataset-ega-egas50000001275"}],"context_names":["Heritable Pulmonary Arterial Hypertension"],"disease_names":["Heritable Pulmonary Arterial Hypertension"],"disease_name":"Heritable Pulmonary Arterial Hypertension","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Heritable_Pulmonary_Arterial_Hypertension.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Heritable_Pulmonary_Arterial_Hypertension.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Heritable_Pulmonary_Arterial_Hypertension.html#dataset-ega-egas50000001275"]},{"id":"dataset:ega:egas50000001317","accession":"ega:EGAS50000001317","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000001317","title":"Immune control of functional memory CD8 T cells in normal-appearing vitiligo skin","alternate_titles":[],"description":"This study aimed to characterize immune cell states in nonlesional (NL) and perilesional (PL) skin of patients with vitiligo using single-cell RNA sequencing. Shared CD8⁺ T cell clusters were detected in both regions, with PL-derived cells enriched for immune activation pathways and NL skin showed stronger infiltration of regulatory T cells. These findings reveal functional T cell heterogeneity in vitiligo and highlight regulatory mechanisms that may limit depigmentation in NL skin.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Vitiligo\"); description-level mentions were not accepted. EGA study_type: Transcriptome Analysis. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Vitiligo","name":"Vitiligo","kind":"Disorder","source_path":"kb/disorders/Vitiligo.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Vitiligo.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Vitiligo.html#dataset-ega-egas50000001317"}],"context_names":["Vitiligo"],"disease_names":["Vitiligo"],"disease_name":"Vitiligo","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Vitiligo.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Vitiligo.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Vitiligo.html#dataset-ega-egas50000001317"]},{"id":"dataset:ega:egas50000001367","accession":"ega:EGAS50000001367","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000001367","title":"Frequent Genetic Alterations in Myositis Autoantigen Genes in Cancer-Associated Dermatomyositis","alternate_titles":[],"description":"One-third of patients diagnosed with dermatomyositis harbor an occult cancer, a rare condition named cancer-associated dermatomyositis (CAD). Emerging evidence suggests that genetic alterations in autoantibody-related genes give rise neoantigens and specific autoantibodies that initiate an autoimmune response characteristic of CAD. This study evaluated the prevalence of such genetic alterations and elucidated molecular mechanisms that may underlie their role in triggering autoimmunity. We detected highly frequent genetic alterations in autoantibody-related genes, supporting their role in the CAD pathogenic mechanisms.","alternate_descriptions":[],"data_types":["WES"],"data_type_labels":["Whole exome sequencing"],"data_type_label":"Whole exome sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Dermatomyositis\"); description-level mentions were not accepted. EGA study_type: Exome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Dermatomyositis","name":"Dermatomyositis","kind":"Disorder","source_path":"kb/disorders/Dermatomyositis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dermatomyositis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Dermatomyositis.html#dataset-ega-egas50000001367"}],"context_names":["Dermatomyositis"],"disease_names":["Dermatomyositis"],"disease_name":"Dermatomyositis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Dermatomyositis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dermatomyositis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Dermatomyositis.html#dataset-ega-egas50000001367"]},{"id":"dataset:ega:egas50000001381","accession":"ega:EGAS50000001381","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000001381","title":"Rosai-Dorfman Disease: Atlas of Blood Cancer Genomes","alternate_titles":[],"description":"Rosai-Dorfman disease (RDD) is a rare histiocytic disorder, most prevalent in children and young adults. The diagnosis of RDD and other histiocytic disorders including Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD) can be challenging as it relies mostly on immunohistochemistry (IHC) of infrequently assayed markers. Little is known about how the gene expression profiles of histiocytic disorders correlate with IHC diagnostic markers, activation of different oncogenic pathways, or components of the microenvironment.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Rosai-Dorfman Disease\"); description-level mentions were not accepted. EGA study_type: Cancer Genomics. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Rosai-Dorfman_Disease","name":"Rosai-Dorfman Disease","kind":"Disorder","source_path":"kb/disorders/Rosai-Dorfman_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rosai-Dorfman_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Rosai-Dorfman_Disease.html#dataset-ega-egas50000001381"}],"context_names":["Rosai-Dorfman Disease"],"disease_names":["Rosai-Dorfman Disease"],"disease_name":"Rosai-Dorfman Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Rosai-Dorfman_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rosai-Dorfman_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Rosai-Dorfman_Disease.html#dataset-ega-egas50000001381"]},{"id":"dataset:ega:egas50000001406","accession":"ega:EGAS50000001406","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000001406","title":"Single-nucleus brain transcriptomics reveals microglia dysfunction in Multiple System Atrophy","alternate_titles":[],"description":"Multiple System Atrophy (MSA) is a rare, age-related neurodegenerative disease that shares clinical and pathological features with Parkinson’s disease (PD) but presents a more devastating disease course. To elucidate the distinct cellular pathophysiology underlying multiple system atrophy (MSA) or Parkinson's disease (PD), we performed single-nucleus RNA sequencing on postmortem striatal brain tissue from 7 MSA and 12 PD patients, and 10 non-neurological cases. Using 10x Genomics Chromium Next GEM Single Cell 3' Reagent Kits v3.1, we isolated 130k nuclei covering all major cell types of the striatum.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Multiple System Atrophy\"); description-level mentions were not accepted. EGA study_type: Transcriptome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Multiple_System_Atrophy","name":"Multiple System Atrophy","kind":"Disorder","source_path":"kb/disorders/Multiple_System_Atrophy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Multiple_System_Atrophy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Multiple_System_Atrophy.html#dataset-ega-egas50000001406"}],"context_names":["Multiple System Atrophy"],"disease_names":["Multiple System Atrophy"],"disease_name":"Multiple System Atrophy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Multiple_System_Atrophy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Multiple_System_Atrophy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Multiple_System_Atrophy.html#dataset-ega-egas50000001406"]},{"id":"dataset:ega:egas50000001412","accession":"ega:EGAS50000001412","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000001412","title":"Axon guidance deficits in a human sensory neuron model of Fabry disease","alternate_titles":[],"description":"We compared gene expression levels of human iPSC derived sensory neurons between an isogenic GLA knockout line and its healthy control as an in Fabry disease in vitro model.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Fabry disease\"); description-level mentions were not accepted. EGA study_type: RNASeq. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Fabry_Disease","name":"Fabry disease","kind":"Disorder","source_path":"kb/disorders/Fabry_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fabry_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Fabry_disease.html#dataset-ega-egas50000001412"}],"context_names":["Fabry disease"],"disease_names":["Fabry disease"],"disease_name":"Fabry disease","same_context_model_ids":["model:kb/disorders/Fabry_Disease.yaml:Fabry patient iPSC-derived cardiomyocyte GL-3 clearance model","model:kb/disorders/Fabry_Disease.yaml:Fabry patient iPSC-derived cardiomyocyte GLA modRNA rescue model","model:kb/disorders/Fabry_Disease.yaml:Female Fabry iPSC-cardiomyocyte high-content drug-screening model","model:kb/disorders/Fabry_Disease.yaml:GLA p.N215S iPSC-derived atrial cardiomyocyte arrhythmia model","model:kb/disorders/Fabry_Disease.yaml:GLA-null hESC-derived cardiomyocyte autophagy and ROS model"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Fabry_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fabry_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Fabry_disease.html#dataset-ega-egas50000001412"]},{"id":"dataset:ega:egas50000001571","accession":"ega:EGAS50000001571","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000001571","title":"Pre-existing immunity and hrHPV status as determinants of immunotherapy response in advanced penile cancer: biomarkers and overall survival in the PERICLES trial","alternate_titles":[],"description":"The phase II PERICLES trial (NCT03686332) investigated atezolizumab with or without radiotherapy in advanced penile cancer. Here, we report mature overall survival (OS) and updated progression-free survival (PFS) outcomes and an in-depth biomarker analysis. The goal was to perform an in-depth assessment of the tumor microenvironment to identify potential predictive biomarkers and cellular mechanisms underlying successful PD-L1 blockade response.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Penile Cancer\"); description-level mentions were not accepted. EGA study_type: RNASeq. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Penile_Cancer","name":"Penile Cancer","kind":"Disorder","source_path":"kb/disorders/Penile_Cancer.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Penile_Cancer.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Penile_Cancer.html#dataset-ega-egas50000001571"}],"context_names":["Penile Cancer"],"disease_names":["Penile Cancer"],"disease_name":"Penile Cancer","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Penile_Cancer.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Penile_Cancer.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Penile_Cancer.html#dataset-ega-egas50000001571"]},{"id":"dataset:ega:egas50000001644","accession":"ega:EGAS50000001644","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000001644","title":"RTEL1 mutation as a modifier of Dyskeratosis Congenita in a family with a Telomerase RNA (hTR) template mutation and variant telomeric repeats","alternate_titles":[],"description":"Vertebrate telomeres, the sequences protecting the end of linear chromosomes, are composed of conserved hexameric GGTTAG repeats. Here we present a C50>A telomerase RNA template mutation that results in the incorporation of the variant telomeric repeat GTTTAG in a family with dyskeratosis congenita primarily presenting as idiopathic pulmonary fibrosis. The mutant telomerase is characterized by decreased processivity in direct telomerase activity assays and in vivo based on data from Illumina next-generation whole genome sequencing and Oxford Nanopore Technologies long-read telomere sequencing.","alternate_descriptions":[],"data_types":["WGS"],"data_type_labels":["Whole genome sequencing"],"data_type_label":"Whole genome sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Dyskeratosis Congenita\"); description-level mentions were not accepted. EGA study_type: Whole Genome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Dyskeratosis_Congenita","name":"Dyskeratosis Congenita","kind":"Disorder","source_path":"kb/disorders/Dyskeratosis_Congenita.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dyskeratosis_Congenita.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Dyskeratosis_Congenita.html#dataset-ega-egas50000001644"}],"context_names":["Dyskeratosis Congenita"],"disease_names":["Dyskeratosis Congenita"],"disease_name":"Dyskeratosis Congenita","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Dyskeratosis_Congenita.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dyskeratosis_Congenita.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Dyskeratosis_Congenita.html#dataset-ega-egas50000001644"]},{"id":"dataset:ega:egas50000001645","accession":"ega:EGAS50000001645","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000001645","title":"Prenatal sodium channel dysfunction in Dravet syndrome alters cortical development","alternate_titles":[],"description":"This dataset contains bulk RNA-sequencing data generated for the study “Prenatal sodium channel dysfunction in Dravet syndrome alters cortical development.” RNA-seq was performed on human cortical organoids and cortical organoid assemblies derived from induced pluripotent stem cells (iPSCs) from two individuals with Dravet syndrome and their corresponding isogenic control lines. Libraries were prepared from total/bulk mRNA and sequenced as paired-end reads. The dataset is intended to enable transcriptomic analyses of early cortical developmental changes associated with Dravet syndrome in an isogenic background.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Dravet syndrome\"); description-level mentions were not accepted. EGA study_type: RNASeq. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Dravet_syndrome","name":"Dravet_syndrome","kind":"Disorder","source_path":"kb/disorders/Dravet_syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dravet_syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Dravet_syndrome.html#dataset-ega-egas50000001645"}],"context_names":["Dravet_syndrome"],"disease_names":["Dravet_syndrome"],"disease_name":"Dravet_syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Dravet_syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dravet_syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Dravet_syndrome.html#dataset-ega-egas50000001645"]},{"id":"dataset:ega:egas50000001808","accession":"ega:EGAS50000001808","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000001808","title":"Integrated Single-Cell and Microbiome Profiling of Stable Bronchiectasis Across Disease Severity","alternate_titles":[],"description":"Bronchiectasis is a chronic respiratory disease characterized by persistent airway inflammation and recurrent infections. In this study, sputum samples from patients with mild, moderate, and severe bronchiectasis, collected during clinically stable disease, were analyzed using flow cytometry, single-cell RNA sequencing, and 16S rRNA gene sequencing. The resulting datasets enable characterization of neutrophil populations, transcriptional states, and airway microbial communities across disease severity stages.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Bronchiectasis\"); description-level mentions were not accepted. EGA study_type: Transcriptome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Bronchiectasis","name":"Bronchiectasis","kind":"Disorder","source_path":"kb/disorders/Bronchiectasis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bronchiectasis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Bronchiectasis.html#dataset-ega-egas50000001808"}],"context_names":["Bronchiectasis"],"disease_names":["Bronchiectasis"],"disease_name":"Bronchiectasis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Bronchiectasis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bronchiectasis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Bronchiectasis.html#dataset-ega-egas50000001808"]},{"id":"dataset:ega:egas50000001887","accession":"ega:EGAS50000001887","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000001887","title":"LRSomatic: Long-read and short-read somatic sequencing of clear cell sarcoma case CCS15","alternate_titles":[],"description":"Whole-genome sequencing of a clinical clear cell sarcoma case (CCS15), comprising a metastatic tumour and matched normal muscle tissue. The tumour and normal were profiled by PacBio HiFi and Oxford Nanopore Fiber-seq (long-read) and by Illumina short-read WGS. Data were generated to benchmark the LRSomatic long-read somatic variant-calling pipeline.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Clear Cell Sarcoma\"); description-level mentions were not accepted. EGA study_type: Cancer Genomics. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Clear_Cell_Sarcoma","name":"Clear Cell Sarcoma","kind":"Disorder","source_path":"kb/disorders/Clear_Cell_Sarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Clear_Cell_Sarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Clear_Cell_Sarcoma.html#dataset-ega-egas50000001887"}],"context_names":["Clear Cell Sarcoma"],"disease_names":["Clear Cell Sarcoma"],"disease_name":"Clear Cell Sarcoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Clear_Cell_Sarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Clear_Cell_Sarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Clear_Cell_Sarcoma.html#dataset-ega-egas50000001887"]},{"id":"dataset:ega:egas50000001944","accession":"ega:EGAS50000001944","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000001944","title":"Establishment of germline-encoded antibodies during primary dengue infection","alternate_titles":[],"description":"This study supports the manuscript “Establishment of germline-encoded antibodies during primary dengue infection” and characterizes longitudinal B cell receptor repertoire dynamics during controlled primary DENV1 infection. Bulk BCR sequencing was performed on whole-blood total RNA from flavivirus-naïve participants in a DENV1 live-virus human challenge study. Samples were collected at days 0, 8, 10, 14, and 28 post-infection, corresponding to pre-infection, early viremic, peak viremic/acute, late viremic/critical-phase, and convalescent timepoints.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Dengue\"); description-level mentions were not accepted. EGA study_type: Transcriptome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Dengue","name":"Dengue","kind":"Disorder","source_path":"kb/disorders/Dengue.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dengue.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Dengue.html#dataset-ega-egas50000001944"}],"context_names":["Dengue"],"disease_names":["Dengue"],"disease_name":"Dengue","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Dengue.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dengue.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Dengue.html#dataset-ega-egas50000001944"]},{"id":"dataset:ega:egas50000001971","accession":"ega:EGAS50000001971","repository":"EGA","accession_url":"https://ega-archive.org/studies/EGAS50000001971","title":"TMEM259 alleles modulate respiratory syncytial virus infection and ER-stress-triggered apoptosis","alternate_titles":[],"description":"Whole Exome Sequencing data for the IRIS1, IRIS2, and IRIS3 cohorts. Abstract: Respiratory syncytial virus (RSV) is a main cause of infant morbidity and mortality. Susceptibility factors for severe RSV bronchiolitis in previously healthy children are unclear. We analyze genetic variants in 5,141 genes involved in virus sensing, interferon (IFN) signaling and effector functions in a population of n=101 previously healthy infants with severe RSV bronchiolitis. Comparing the allele frequencies of the patient cohort with the Exome Aggregation Consortium (ExAC) dataset our analysis reveals 94 non-synonymous coding single nucleotide polymorphisms (SNPs) mapping to 79 potential risk genes.","alternate_descriptions":[],"data_types":["WES"],"data_type_labels":["Whole exome sequencing"],"data_type_label":"Whole exome sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["European Genome-phenome Archive study, matched because the disease is named in the study's own title (\"Respiratory Syncytial Virus Infection\"); description-level mentions were not accepted. EGA study_type: Exome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01."],"contexts":[{"id":"disorder:Respiratory_Syncytial_Virus_Infection","name":"Respiratory Syncytial Virus Infection","kind":"Disorder","source_path":"kb/disorders/Respiratory_Syncytial_Virus_Infection.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Respiratory_Syncytial_Virus_Infection.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Respiratory_Syncytial_Virus_Infection.html#dataset-ega-egas50000001971"}],"context_names":["Respiratory Syncytial Virus Infection"],"disease_names":["Respiratory Syncytial Virus Infection"],"disease_name":"Respiratory Syncytial Virus Infection","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Respiratory_Syncytial_Virus_Infection.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Respiratory_Syncytial_Virus_Infection.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Respiratory_Syncytial_Virus_Infection.html#dataset-ega-egas50000001971"]},{"id":"dataset:geo:gds1096","accession":"geo:GDS1096","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GDS1096","title":"Expression Proflies of Human Normal tissues","alternate_titles":[],"description":"Normal human tissue expression atlas used in the founding report to prioritize COX4I2 through a bone-marrow expression profile (probe 212312_at). It is a background expression resource, not a dataset of EPIDACH patients.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:16232","label":"COX4I2","display_label":"COX4I2","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/16232"}],"genes":["COX4I2"],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"url:https://pmc.ncbi.nlm.nih.gov/articles/PMC2668012/","reference_url":null,"reference_title":"Exocrine Pancreatic Insufficiency, Dyserythropoeitic Anemia, and Calvarial Hyperostosis Are Caused by a Mutation in the COX4I2 Gene - PMC","supports":"SUPPORT","evidence_source":"COMPUTATIONAL","snippet":"this gene was highly expressed in bone marrow (GEO profiles: GDS1096/212312_at /COX4I2).","explanation":"The original report explicitly identifies the accession and probe used for candidate prioritization."}],"notes":["The repository describes expression profiling across 36 normal human tissue types using pooled donor RNA. Tissue expression does not establish disease causality or a patient-specific expression defect."],"contexts":[{"id":"disorder:COX4I2-Related_Pancreatic_Insufficiency-Anemia-Hyperostosis_Syndrome","name":"COX4I2-Related Pancreatic Insufficiency-Anemia-Hyperostosis Syndrome","kind":"Disorder","source_path":"kb/disorders/COX4I2-Related_Pancreatic_Insufficiency-Anemia-Hyperostosis_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/COX4I2-Related_Pancreatic_Insufficiency-Anemia-Hyperostosis_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/COX4I2-Related_Pancreatic_Insufficiency-Anemia-Hyperostosis_Syndrome.html#dataset-geo-gds1096"}],"context_names":["COX4I2-Related Pancreatic Insufficiency-Anemia-Hyperostosis Syndrome"],"disease_names":["COX4I2-Related Pancreatic Insufficiency-Anemia-Hyperostosis Syndrome"],"disease_name":"COX4I2-Related Pancreatic Insufficiency-Anemia-Hyperostosis Syndrome","same_context_model_ids":["model:kb/disorders/COX4I2-Related_Pancreatic_Insufficiency-Anemia-Hyperostosis_Syndrome.yaml:COX4 isoform replacement in HEK293 cells","model:kb/disorders/COX4I2-Related_Pancreatic_Insufficiency-Anemia-Hyperostosis_Syndrome.yaml:COX4I2 perturbation in pulmonary arterial smooth muscle cells","model:kb/disorders/COX4I2-Related_Pancreatic_Insufficiency-Anemia-Hyperostosis_Syndrome.yaml:E138K patient fibroblast cultures"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/COX4I2-Related_Pancreatic_Insufficiency-Anemia-Hyperostosis_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/COX4I2-Related_Pancreatic_Insufficiency-Anemia-Hyperostosis_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/COX4I2-Related_Pancreatic_Insufficiency-Anemia-Hyperostosis_Syndrome.html#dataset-geo-gds1096"]},{"id":"dataset:geo:gse100488","accession":"geo:GSE100488","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE100488","title":"Circulating miRNome profiling in Moyamoya disease-discordant monozygotic twins and endothelial microRNA expression analysis using iPS cell line","alternate_titles":[],"description":"We aim to investigate circulating genome-wide microRNA (miRome) profiles in Moyamoya disease (MMD)-discordant monozygotic (MZ) twins with the RNF213 founder mutation (rs112735431).A disease discordant monozygotic twin-based study design may unmask potential confounders from previously published circulating microRNA signature in MMD. Circulating genome-wide microRNA (miRNome) profiling was performed in MMD-discordant monozygotic twins, non-twin-MMD patients, and non-MMD healthy volunteers by microarray followed by qPCRvalidation, using blood samples.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[21],"sample_count":21,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:30157848"],"publication_contexts":[{"context_id":"disorder:Moyamoya_Disease","publication":"PMID:30157848"}],"publication":"PMID:30157848","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/30157848","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Moyamoya Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Moyamoya_Disease","name":"Moyamoya Disease","kind":"Disorder","source_path":"kb/disorders/Moyamoya_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Moyamoya_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Moyamoya_Disease.html#dataset-geo-gse100488"}],"context_names":["Moyamoya Disease"],"disease_names":["Moyamoya Disease"],"disease_name":"Moyamoya Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Moyamoya_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Moyamoya_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Moyamoya_Disease.html#dataset-geo-gse100488"]},{"id":"dataset:geo:gse101486","accession":"geo:GSE101486","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE101486","title":"Genome-wide analysis of prostatic tissue gene expression from patients with benign prostatic hyperplasia","alternate_titles":[],"description":"Analysis of gene expression in prostatic tissue from BPH patients with and without SRD5A2 gene methylation. The hypothesis is that BPH patients with DNA methylation of the SRD5A2 gene promoter have impaired conversion of testosterone to dihydrotestosterone, and therefore may use an alternative signaling pathway for prostatic tissue growth. Here, we compare gene expression profiles of SRD5A2-methylated vs. unmethylated prostatic tissue to nominate alternative biological pathways relevant in each molecular subtype of BPH.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[22],"sample_count":22,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:28940538"],"publication_contexts":[{"context_id":"disorder:Benign_Prostatic_Hyperplasia","publication":"PMID:28940538"}],"publication":"PMID:28940538","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/28940538","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Benign Prostatic Hyperplasia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Benign_Prostatic_Hyperplasia","name":"Benign Prostatic Hyperplasia","kind":"Disorder","source_path":"kb/disorders/Benign_Prostatic_Hyperplasia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Benign_Prostatic_Hyperplasia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Benign_Prostatic_Hyperplasia.html#dataset-geo-gse101486"}],"context_names":["Benign Prostatic Hyperplasia"],"disease_names":["Benign Prostatic Hyperplasia"],"disease_name":"Benign Prostatic Hyperplasia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Benign_Prostatic_Hyperplasia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Benign_Prostatic_Hyperplasia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Benign_Prostatic_Hyperplasia.html#dataset-geo-gse101486"]},{"id":"dataset:geo:gse10167","accession":"geo:GSE10167","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE10167","title":"Microarray Analysis of Treacher Collins Syndrome","alternate_titles":[],"description":"Whole-embryo expression profiling of three E8.5 Tcof1+/- mouse embryos and three wild-type littermates, generated to identify transcriptional changes associated with Tcof1 haploinsufficiency.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":["E8.5 Tcof1+/- littermate embryo","E8.5 wild-type littermate embryo"],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:11654","label":"TCOF1","display_label":"TCOF1","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/11654"}],"genes":["TCOF1"],"platforms":["Affymetrix GeneChip Mouse Genome 430 2.0 array (GPL1261)"],"platform":"Affymetrix GeneChip Mouse Genome 430 2.0 array (GPL1261)","publications":["PMID:18246078"],"publication_contexts":[{"context_id":"disorder:Treacher_Collins_Syndrome","publication":"PMID:18246078"}],"publication":"PMID:18246078","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/18246078","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"url:https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE10167","reference_url":null,"reference_title":"GEO Accession viewer","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"Total RNA was extracted from 3 E8.5 wild-type and 3 E8.5 Tcof1+/- littermate embryos","explanation":"The GEO record verifies the genotype groups, developmental stage, and sample count."}],"notes":["Direct disease-model dataset linked to the p53-rescue study. Because RNA is from whole embryos rather than isolated cranial neural crest, cell-type specificity cannot be inferred directly from this dataset alone."],"contexts":[{"id":"disorder:Treacher_Collins_Syndrome","name":"Treacher Collins Syndrome","kind":"Disorder","source_path":"kb/disorders/Treacher_Collins_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Treacher_Collins_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Treacher_Collins_Syndrome.html#dataset-geo-gse10167"}],"context_names":["Treacher Collins Syndrome"],"disease_names":["Treacher Collins Syndrome"],"disease_name":"Treacher Collins Syndrome","same_context_model_ids":["model:kb/disorders/Treacher_Collins_Syndrome.yaml:TCOF1-Haploinsufficient Human Pluripotent Stem Cell-Derived Neural Crest Model"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Treacher_Collins_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Treacher_Collins_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Treacher_Collins_Syndrome.html#dataset-geo-gse10167"]},{"id":"dataset:geo:gse102128","accession":"geo:GSE102128","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE102128","title":"RNA-seq of hiPSCs-derived NPCs from 3 pairs of dizygotic discordant twins for Congenital Zika syndrome","alternate_titles":[],"description":"Congenital Zika syndrome (CZS), caused by Zika virus (ZIKV) infection, has been associated to impairment of early brain development, particularly related to neural progenitor cells (NPCs) survival and growth. In this work we report in a high-throughput manner (RNA-Seq) the differences in the transcriptomes of hiPSCs(human induced pluripotent stem cells)-derived NPCs from 3 pairs of discordant twins for Congenital Zika syndrome (CZS).","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:29396410"],"publication_contexts":[{"context_id":"disorder:Congenital_Zika_Syndrome","publication":"PMID:29396410"}],"publication":"PMID:29396410","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/29396410","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Congenital Zika Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Congenital_Zika_Syndrome","name":"Congenital Zika Syndrome","kind":"Disorder","source_path":"kb/disorders/Congenital_Zika_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Congenital_Zika_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Congenital_Zika_Syndrome.html#dataset-geo-gse102128"}],"context_names":["Congenital Zika Syndrome"],"disease_names":["Congenital Zika Syndrome"],"disease_name":"Congenital Zika Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Congenital_Zika_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Congenital_Zika_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Congenital_Zika_Syndrome.html#dataset-geo-gse102128"]},{"id":"dataset:geo:gse102138","accession":"geo:GSE102138","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE102138","title":"Transcriptional profiling identifies differential expression of long non-coding RNAs in Jo-1 associated and inclusion body myositis","alternate_titles":[],"description":"Myositis is characterised by muscle inflammation and weakness. Although generally thought to be driven by a systemic autoimmune response, increasing evidence suggests that intrinsic changes in the muscle might also contribute to the pathogenesis. Long non-coding RNAs (lncRNAs) are a family of novel genes that regulate gene transcription and translation. To determine the potential role of lncRNAs, we employed next generation sequencing to examine the transcriptome in muscle biopsies obtained from two histologically distinct patient populations, inclusion body myositis (IBM) and anti-Jo-1-associated myositis (Jo-1).","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:28808260"],"publication_contexts":[{"context_id":"disorder:Inclusion_Body_Myositis","publication":"PMID:28808260"}],"publication":"PMID:28808260","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/28808260","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Inclusion Body Myositis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Inclusion_Body_Myositis","name":"Inclusion Body Myositis","kind":"Disorder","source_path":"kb/disorders/Inclusion_Body_Myositis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Inclusion_Body_Myositis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Inclusion_Body_Myositis.html#dataset-geo-gse102138"}],"context_names":["Inclusion Body Myositis"],"disease_names":["Inclusion Body Myositis"],"disease_name":"Inclusion Body Myositis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Inclusion_Body_Myositis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Inclusion_Body_Myositis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Inclusion_Body_Myositis.html#dataset-geo-gse102138"]},{"id":"dataset:geo:gse103460","accession":"geo:GSE103460","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE103460","title":"Dynamic transcriptome analysis of human erythroind progenetor cells infected by human Parvovirus B19","alternate_titles":[],"description":"Human parvovirus B19 (B19V) infection can cause transient aplastic crisis, persistent viremia, and pure red-cell aplasia. In fetuses, B19V infection can result in non-immune hydrops fetalis and fetal death. To systematically investigate the interaction between B19V and erythoid progenetor cells (EPC), microarray was applied to systematically analyze the dynamic transcriptome of CD36+ EPCs during B19V infection.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[15],"sample_count":15,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:29237843"],"publication_contexts":[{"context_id":"disorder:Parvovirus_B19_Infection","publication":"PMID:29237843"}],"publication":"PMID:29237843","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/29237843","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Parvovirus B19 Infection (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Parvovirus_B19_Infection","name":"Parvovirus B19 Infection","kind":"Disorder","source_path":"kb/disorders/Parvovirus_B19_Infection.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Parvovirus_B19_Infection.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Parvovirus_B19_Infection.html#dataset-geo-gse103460"}],"context_names":["Parvovirus B19 Infection"],"disease_names":["Parvovirus B19 Infection"],"disease_name":"Parvovirus B19 Infection","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Parvovirus_B19_Infection.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Parvovirus_B19_Infection.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Parvovirus_B19_Infection.html#dataset-geo-gse103460"]},{"id":"dataset:geo:gse104922","accession":"geo:GSE104922","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE104922","title":"Molecular subtype classification of urothelial carcinoma in Lynch syndrome","alternate_titles":[],"description":"Microarray cohort of Lynch syndrome-associated urothelial cancers from bladder and upper urinary tract, profiled for molecular subtype mapping, MSI status, and clinicopathologic associations.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0001255","label":"urinary bladder","display_label":"urinary bladder tumor tissue","url":"http://purl.obolibrary.org/obo/UBERON_0001255"},{"id":"UBERON:0011143","label":"upper urinary tract","display_label":"upper urinary tract tumor tissue","url":"http://purl.obolibrary.org/obo/UBERON_0011143"}],"sample_type_labels":["urinary bladder","upper urinary tract"],"sample_counts":[41],"sample_count":41,"conditions":["Lynch syndrome urothelial carcinoma","upper urinary tract urothelial carcinoma","bladder urothelial carcinoma"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["Affymetrix Human Gene 1.0 ST Array"],"platform":"Affymetrix Human Gene 1.0 ST 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molecular subtypes."],"contexts":[{"id":"disorder:Lynch_Syndrome","name":"Lynch Syndrome","kind":"Disorder","source_path":"kb/disorders/Lynch_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Lynch_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Lynch_Syndrome.html#dataset-geo-gse104922"}],"context_names":["Lynch Syndrome"],"disease_names":["Lynch Syndrome"],"disease_name":"Lynch Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association 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mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":["non-infected control macrophages","virulent-strain infection","attenuated-strain infection","saprophytic-strain infection"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:30129936"],"publication_contexts":[{"context_id":"disorder:Leptospirosis","publication":"PMID:30129936"}],"publication":"PMID:30129936","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/30129936","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE105104","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE105104","reference_title":"MicroRNA profiles of murine macrophages infected with different strains of Leptospira 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recorded","source_paths":["kb/disorders/Leptospirosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Leptospirosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Leptospirosis.html#dataset-geo-gse105104"]},{"id":"dataset:geo:gse106302","accession":"geo:GSE106302","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE106302","title":"Hippocampal gene expression from Nr2f1 heterozygous knockout and WT mice","alternate_titles":[],"description":"Bulk RNA-seq comparing adult hippocampi from Nr2f1 heterozygous knockout mice with wild-type controls, associated with the mouse-model study of BBSOAS neurologic phenotypes and synaptic plasticity.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus 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recorded","findings":[],"findings_text":[],"evidence":[{"reference":"url:https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE106302","reference_url":null,"reference_title":"GEO Accession viewer","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"RNA-seq of hippocampus from Nr2f1 heterozygous knockout and WT mice.","explanation":"The GEO record supplies the accession, tissue, perturbation, and assay."}],"notes":[],"contexts":[{"id":"disorder:Bosch-Boonstra-Schaaf_Optic_Atrophy_Syndrome","name":"Bosch-Boonstra-Schaaf Optic Atrophy Syndrome","kind":"Disorder","source_path":"kb/disorders/Bosch-Boonstra-Schaaf_Optic_Atrophy_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bosch-Boonstra-Schaaf_Optic_Atrophy_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Bosch-Boonstra-Schaaf_Optic_Atrophy_Syndrome.html#dataset-geo-gse106302"}],"context_names":["Bosch-Boonstra-Schaaf Optic Atrophy Syndrome"],"disease_names":["Bosch-Boonstra-Schaaf Optic Atrophy Syndrome"],"disease_name":"Bosch-Boonstra-Schaaf Optic Atrophy Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Bosch-Boonstra-Schaaf_Optic_Atrophy_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bosch-Boonstra-Schaaf_Optic_Atrophy_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Bosch-Boonstra-Schaaf_Optic_Atrophy_Syndrome.html#dataset-geo-gse106302"]},{"id":"dataset:geo:gse106500","accession":"geo:GSE106500","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE106500","title":"Immune Profiling of Premalignant Lesions in Patients with Lynch Syndrome","alternate_titles":[],"description":"RNA-seq cohort of colorectal adenomas from Lynch syndrome patients, with comparator familial adenomatous polyposis adenomas, used for transcriptomic immune profiling of premalignant lesions.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0001155","label":"colon","display_label":"colorectal adenoma tissue","url":"http://purl.obolibrary.org/obo/UBERON_0001155"}],"sample_type_labels":["colon"],"sample_counts":[24],"sample_count":24,"conditions":["Lynch syndrome colorectal adenoma","familial adenomatous polyposis colorectal adenoma"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["Illumina HiSeq 2000"],"platform":"Illumina HiSeq 2000","publications":["PMID:29710228"],"publication_contexts":[{"context_id":"disorder:Lynch_Syndrome","publication":"PMID:29710228"}],"publication":"PMID:29710228","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/29710228","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:29710228","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/29710228","reference_title":"Immune Profiling of Premalignant Lesions in Patients With Lynch Syndrome.","supports":"SUPPORT","evidence_source":null,"snippet":"Whole-genome transcriptomic analysis using next-generation sequencing was performed in colorectal polyps and carcinomas of patients with LS.","explanation":"This directly supports transcriptomic sequencing in Lynch syndrome colorectal premalignant/tumor lesions relevant to this GEO cohort."}],"notes":["Focuses on early lesion immune activation and checkpoint biology in LS, useful for mechanistic chemoprevention and interception studies."],"contexts":[{"id":"disorder:Lynch_Syndrome","name":"Lynch Syndrome","kind":"Disorder","source_path":"kb/disorders/Lynch_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Lynch_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Lynch_Syndrome.html#dataset-geo-gse106500"}],"context_names":["Lynch Syndrome"],"disease_names":["Lynch Syndrome"],"disease_name":"Lynch Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Lynch_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Lynch_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Lynch_Syndrome.html#dataset-geo-gse106500"]},{"id":"dataset:geo:gse106961","accession":"geo:GSE106961","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE106961","title":"Conjunctival transcriptome profiling of Solomon Islanders with active trachoma but without ocular Chlamydia trachomatis infection.","alternate_titles":[],"description":"The prevalence of trachomatous inflammation–follicular (TF) in Solomon Island children aged 1–9 years is high enough to warrant, among other interventions, mass distribution of azithromycin. However, over 90% of those with TF did not have concurrent Chlamydia trachomatis infection. We analysed the transcriptome of children with TF and Ct infection, children diagnosed with TF but no Ct infection and children with neither TF nor Ct infection to better understand host responses during an episode of TF, and investigate whether it can provide any clues about the aetiology of TF in this context.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[20],"sample_count":20,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:29467021"],"publication_contexts":[{"context_id":"disorder:Trachoma","publication":"PMID:29467021"}],"publication":"PMID:29467021","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/29467021","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Trachoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Trachoma","name":"Trachoma","kind":"Disorder","source_path":"kb/disorders/Trachoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Trachoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Trachoma.html#dataset-geo-gse106961"}],"context_names":["Trachoma"],"disease_names":["Trachoma"],"disease_name":"Trachoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Trachoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Trachoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Trachoma.html#dataset-geo-gse106961"]},{"id":"dataset:geo:gse107554","accession":"geo:GSE107554","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE107554","title":"Evaluation of immunological factors involved in initiation of chronic brucellosis in CD4+ T cells using miRNA array","alternate_titles":[],"description":"Brucellosis is a serious infectious disease and continues to be an important cause of morbidity. It can be seen almost anywhere in the world and at any age. Acute phase heals or becomes chronic form. Infection of 10-30% of patients becomes chronic, despite early diagnosis and treatment. Although our knowledge about Brucella virulence factors and the host response increase rapidly, how they can hidden from the immune system and cause chronic disease are still unknown. We aimed to investigate the immunological factors which belong to CD4+ T cells and their roles in the transition of brucellosis from acute to chronic infection.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[23],"sample_count":23,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:29897958"],"publication_contexts":[{"context_id":"disorder:Brucellosis","publication":"PMID:29897958"}],"publication":"PMID:29897958","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/29897958","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Brucellosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Brucellosis","name":"Brucellosis","kind":"Disorder","source_path":"kb/disorders/Brucellosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Brucellosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Brucellosis.html#dataset-geo-gse107554"}],"context_names":["Brucellosis"],"disease_names":["Brucellosis"],"disease_name":"Brucellosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Brucellosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Brucellosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Brucellosis.html#dataset-geo-gse107554"]},{"id":"dataset:geo:gse107878","accession":"geo:GSE107878","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE107878","title":"Disruption of Autism Spectrum Disorder-Susceptibility Genes Predominantly Reduces Functional Connectivity of Isogenic Human Neurons","alternate_titles":[],"description":"Autism Spectrum Disorder (ASD) is phenotypically and genetically heterogeneous, but genomic analyses have identified candidate susceptibility genes. We present a CRISPR gene editing strategy to insert a protein tag and premature termination sites creating an induced pluripotent stem cell (iPSC) knockout resource for functional studies of 10 ASD-relevant genes (AFF2/FMR2, ANOS1, ASTN2, ATRX, CACNA1C, CHD8, DLGAP2, KCNQ2, SCN2A, TENM1). Neurogenin 2 (NEUROG2)-directed differentiation of iPSCs allowed production of cortical excitatory neurons, and mutant proteins were not detectable.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[86],"sample_count":86,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:30392976"],"publication_contexts":[{"context_id":"disorder:Autism_Spectrum_Disorder","publication":"PMID:30392976"}],"publication":"PMID:30392976","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/30392976","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Autism Spectrum Disorder (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Autism_Spectrum_Disorder","name":"Autism Spectrum Disorder","kind":"Disorder","source_path":"kb/disorders/Autism_Spectrum_Disorder.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autism_Spectrum_Disorder.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autism_Spectrum_Disorder.html#dataset-geo-gse107878"}],"context_names":["Autism Spectrum Disorder"],"disease_names":["Autism Spectrum Disorder"],"disease_name":"Autism Spectrum Disorder","same_context_model_ids":["model:kb/disorders/Autism_Spectrum_Disorder.yaml:Genotype-defined patient iPSC-derived neuronal networks","model:kb/disorders/Autism_Spectrum_Disorder.yaml:Multi-genotype human cortical organoid and neural-progenitor panel"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Autism_Spectrum_Disorder.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autism_Spectrum_Disorder.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Autism_Spectrum_Disorder.html#dataset-geo-gse107878"]},{"id":"dataset:geo:gse107963","accession":"geo:GSE107963","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE107963","title":"Mutations of Wiskott-Aldrich Syndrome Protein cause oncogenic cell cycle dysreguation through disruption of alternative Splicing and epigenetic mechanisms","alternate_titles":[],"description":"Wiskott-Aldrich syndrome (WAS), which is caused by mutations in the gene encoding WASP, manifests in a wide range of hematologic and immune dysfunctions and predisposition to cancer development 1. WASP is most known as a cytoplasmic effector of actin cytoskeleton rearrangement. However, defective actin polymerization cannot explain many aspects of WAS pathogenesis. Incomplete knowledge of WASP function precludes in-depth understanding of the underlying mechanisms of WAS, and therefore hampers the development of effective therapies.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[21],"sample_count":21,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:35752626"],"publication_contexts":[{"context_id":"disorder:Wiskott_Aldrich_Syndrome","publication":"PMID:35752626"}],"publication":"PMID:35752626","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35752626","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Wiskott-Aldrich syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Wiskott_Aldrich_Syndrome","name":"Wiskott-Aldrich syndrome","kind":"Disorder","source_path":"kb/disorders/Wiskott_Aldrich_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Wiskott_Aldrich_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Wiskott-Aldrich_syndrome.html#dataset-geo-gse107963"}],"context_names":["Wiskott-Aldrich syndrome"],"disease_names":["Wiskott-Aldrich syndrome"],"disease_name":"Wiskott-Aldrich syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Wiskott_Aldrich_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Wiskott_Aldrich_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Wiskott-Aldrich_syndrome.html#dataset-geo-gse107963"]},{"id":"dataset:geo:gse108200","accession":"geo:GSE108200","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE108200","title":"Frataxin deficiency in Friedreich?s Ataxia is associated with reduced levels of HAX-1, a regulator of cardiomyocyte death and survival.","alternate_titles":[],"description":"Microarray profiling of FRDA patient lymphoblastoid cells with and without stable frataxin reconstitution, the screen that nominated HAX-1 as a candidate cardiomyopathy biomarker.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[2],"sample_count":2,"conditions":["FRDA lymphoblastoid cells, frataxin reconstituted","FRDA lymphoblastoid cells, empty vector"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:31943004"],"publication_contexts":[{"context_id":"disorder:Friedreich_Ataxia","publication":"PMID:31943004"}],"publication":"PMID:31943004","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/31943004","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE108200","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE108200","reference_title":"Frataxin deficiency in Friedreich?s Ataxia is associated with reduced levels of HAX-1, a regulator of cardiomyocyte death and survival.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"To identify other genes involved in pathogenesis of FRDA, a microarray analysis on FRDA patient's lymphoblastoid cells stably reconstituted with FXN was performed.","explanation":"The GEO summary describes the frataxin-reconstitution microarray comparison held in this series."}],"notes":["GEO's own title spells the disease \"Friedreich?s Ataxia\"; the title is copied verbatim as the repository records it. Only two array samples are deposited, so the series is the discovery screen rather than the paper's full patient cohort."],"contexts":[{"id":"disorder:Friedreich_Ataxia","name":"Friedreich Ataxia","kind":"Disorder","source_path":"kb/disorders/Friedreich_Ataxia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Friedreich_Ataxia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Friedreich_Ataxia.html#dataset-geo-gse108200"}],"context_names":["Friedreich Ataxia"],"disease_names":["Friedreich Ataxia"],"disease_name":"Friedreich Ataxia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Friedreich_Ataxia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Friedreich_Ataxia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Friedreich_Ataxia.html#dataset-geo-gse108200"]},{"id":"dataset:geo:gse10846","accession":"geo:GSE10846","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE10846","title":"Prediction of survival in diffuse large B cell lymphoma treated with chemotherapy plus Rituximab","alternate_titles":[],"description":"Gene expression microarray dataset of 414 diffuse large B-cell lymphoma cases used for molecular subtype and outcome analyses.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0000029","label":"lymph node","display_label":"lymph node","url":"http://purl.obolibrary.org/obo/UBERON_0000029"}],"sample_type_labels":["lymph node"],"sample_counts":[414],"sample_count":414,"conditions":["diffuse large B-cell lymphoma"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Large lymphoma cohort frequently used for subtype and survival studies."],"contexts":[{"id":"disorder:Lymphoma","name":"Lymphoma","kind":"Disorder","source_path":"kb/disorders/Lymphoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Lymphoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Lymphoma.html#dataset-geo-gse10846"}],"context_names":["Lymphoma"],"disease_names":["Lymphoma"],"disease_name":"Lymphoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Lymphoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Lymphoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Lymphoma.html#dataset-geo-gse10846"]},{"id":"dataset:geo:gse108849","accession":"geo:GSE108849","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE108849","title":"Single-cell RNA-seq of fibroblasts from recessive dystrophic epidermolysis bullosa patients and wild-type controls","alternate_titles":[],"description":"Human single-cell transcriptomic dataset profiling fibroblast populations from recessive dystrophic epidermolysis bullosa and control samples to resolve disease-relevant stromal heterogeneity.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[543],"sample_count":543,"conditions":["recessive dystrophic epidermolysis bullosa fibroblasts","wild-type control fibroblasts"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE108849","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE108849","reference_title":"Single-cell RNA-seq of fibroblasts from recessive dystrophic epidermolysis bullosa patients and wild-type controls","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The goal of this study is to discover fibroblast subpopulations relevant to recessive dystrophic epidermolysis bullosa","explanation":"Directly supports this GEO series as a single-cell fibroblast resource for DEB mechanism studies."}],"notes":[],"contexts":[{"id":"disorder:Dystrophic_Epidermolysis_Bullosa","name":"Dystrophic Epidermolysis Bullosa","kind":"Disorder","source_path":"kb/disorders/Dystrophic_Epidermolysis_Bullosa.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dystrophic_Epidermolysis_Bullosa.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Dystrophic_Epidermolysis_Bullosa.html#dataset-geo-gse108849"}],"context_names":["Dystrophic Epidermolysis Bullosa"],"disease_names":["Dystrophic Epidermolysis Bullosa"],"disease_name":"Dystrophic Epidermolysis Bullosa","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Dystrophic_Epidermolysis_Bullosa.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dystrophic_Epidermolysis_Bullosa.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Dystrophic_Epidermolysis_Bullosa.html#dataset-geo-gse108849"]},{"id":"dataset:geo:gse109515","accession":"geo:GSE109515","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE109515","title":"The Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis Study (GRADS)  Alpha-1 study [A1AT]","alternate_titles":[],"description":"Whole genome mRNA and microRNA profiling of bronchoalveolar lavage (BAL) and peripheral blood mononuclear cell (PBMC) in Alpha-1 Antitrypsin Deficiency patients with PiZZ or PiMZ alpha-1 antitrypsin genotypes","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[178],"sample_count":178,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:33303696"],"publication_contexts":[{"context_id":"disorder:Alpha_1_Antitrypsin_Deficiency","publication":"PMID:33303696"}],"publication":"PMID:33303696","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/33303696","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Alpha-1 Antitrypsin Deficiency (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Alpha_1_Antitrypsin_Deficiency","name":"Alpha-1 Antitrypsin Deficiency","kind":"Disorder","source_path":"kb/disorders/Alpha_1_Antitrypsin_Deficiency.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alpha_1_Antitrypsin_Deficiency.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Alpha-1_Antitrypsin_Deficiency.html#dataset-geo-gse109515"}],"context_names":["Alpha-1 Antitrypsin Deficiency"],"disease_names":["Alpha-1 Antitrypsin Deficiency"],"disease_name":"Alpha-1 Antitrypsin Deficiency","same_context_model_ids":["model:kb/disorders/Alpha_1_Antitrypsin_Deficiency.yaml:CRISPR-engineered Huh7.5Z hepatocyte cell line"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Alpha_1_Antitrypsin_Deficiency.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alpha_1_Antitrypsin_Deficiency.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Alpha-1_Antitrypsin_Deficiency.html#dataset-geo-gse109515"]},{"id":"dataset:geo:gse109558","accession":"geo:GSE109558","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE109558","title":"Proinflammatory cytokines and response to molds in mononuclear cells of patients with Meniere disease, vestibular migarine and Healthy controls","alternate_titles":[],"description":"Analysis of PBMC gene expression level before and after stimulation with Aspergillus or Penicillium","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[41],"sample_count":41,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:29654306"],"publication_contexts":[{"context_id":"disorder:Menieres_Disease","publication":"PMID:29654306"}],"publication":"PMID:29654306","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/29654306","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Meniere's Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Menieres_Disease","name":"Meniere's Disease","kind":"Disorder","source_path":"kb/disorders/Menieres_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Menieres_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Meniere's_Disease.html#dataset-geo-gse109558"}],"context_names":["Meniere's Disease"],"disease_names":["Meniere's Disease"],"disease_name":"Meniere's Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Menieres_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Menieres_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Meniere's_Disease.html#dataset-geo-gse109558"]},{"id":"dataset:geo:gse110146","accession":"geo:GSE110146","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE110146","title":"Transcriptomic-based functional characterization of adverse events following lymphatic filariasis treatment","alternate_titles":[],"description":"Intro: Lymphatic filariasis (LF) is a neglected tropical disease caused by the nematode parasite Wuchereria bancrofti. The primary tool used by the Global Program to Eliminate LF is mass drug administration (MDA), and some 500 million people take the medications each year. Mild to moderate adverse events (AEs) are common after LF treatment, and these pose a challenge for the LF elimination program. To better understand the pathogenesis of AEs, we studied patients from a LF treatment trial in Côte d’Ivoire. Method: Total RNA was extracted from peripheral blood leukocytes collected before and 24h after treatment (when AEs peak).","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[38],"sample_count":38,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:31557154"],"publication_contexts":[{"context_id":"disorder:Lymphatic_Filariasis","publication":"PMID:31557154"}],"publication":"PMID:31557154","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/31557154","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Lymphatic filariasis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Lymphatic_Filariasis","name":"Lymphatic filariasis","kind":"Disorder","source_path":"kb/disorders/Lymphatic_Filariasis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Lymphatic_Filariasis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Lymphatic_filariasis.html#dataset-geo-gse110146"}],"context_names":["Lymphatic filariasis"],"disease_names":["Lymphatic filariasis"],"disease_name":"Lymphatic filariasis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Lymphatic_Filariasis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Lymphatic_Filariasis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Lymphatic_filariasis.html#dataset-geo-gse110146"]},{"id":"dataset:geo:gse111436","accession":"geo:GSE111436","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE111436","title":"dCas9-based Scn1a gene activation restores inhibitory interneuron excitability and restrains epileptic crises in Dravet syndrome mice","alternate_titles":[],"description":"Dravet syndrome (DS) is a severe epileptic encephalopathy caused by heterozygous loss-of-function mutations in the SCN1A gene, indicating a haploinsufficient genetic mechanism underlining this pathology. Here, we tested whether dCas9-mediated Scn1a gene activation could rescue Scn1a haploinsufficiency and restore physiological levels of its gene product, the Nav1.1 voltage-gated sodium channel. We screeened sgRNAs for their ability to stimulate Scn1a gene transcription in association with the dCas9 activation system. Interestingly, we identified one single sgRNA able to significantly increase Scn1a gene expression levels in cell lines as well as in primary neurons, with high specificity.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:31607539"],"publication_contexts":[{"context_id":"disorder:Dravet_syndrome","publication":"PMID:31607539"}],"publication":"PMID:31607539","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/31607539","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Dravet syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Dravet_syndrome","name":"Dravet_syndrome","kind":"Disorder","source_path":"kb/disorders/Dravet_syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dravet_syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Dravet_syndrome.html#dataset-geo-gse111436"}],"context_names":["Dravet_syndrome"],"disease_names":["Dravet_syndrome"],"disease_name":"Dravet_syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Dravet_syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dravet_syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Dravet_syndrome.html#dataset-geo-gse111436"]},{"id":"dataset:geo:gse111672","accession":"geo:GSE111672","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE111672","title":"Integrating microarray-based spatial transcriptomics and single-cell RNA-seq reveals tissue architecture in pancreatic ductal adenocarcinomas","alternate_titles":[],"description":"Multimodal PDAC dataset combining spatial transcriptomics and single-cell RNA-seq from primary pancreatic tumors. Useful for resolving how malignant ductal cells, macrophages, dendritic cells, and fibroblast states are spatially organized within the tumor microenvironment.","alternate_descriptions":[],"data_types":["MULTI_OMICS"],"data_type_labels":["Multi Omics"],"data_type_label":"Multi Omics","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0001264","label":"pancreas","display_label":"pancreas","url":"http://purl.obolibrary.org/obo/UBERON_0001264"}],"sample_type_labels":["pancreas"],"sample_counts":[23],"sample_count":23,"conditions":["primary pancreatic ductal adenocarcinoma"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:31932730"],"publication_contexts":[{"context_id":"disorder:Pancreatic_Ductal_Adenocarcinoma","publication":"PMID:31932730"}],"publication":"PMID:31932730","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/31932730","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["GEO has 23 sample records derived from six patients with single-cell and spatial measurements. Assay/sample count is not the number of independent patient tumors. Spatial colocalization supports ecological hypotheses but not causal cell-cell signaling."],"contexts":[{"id":"disorder:Pancreatic_Ductal_Adenocarcinoma","name":"Pancreatic Ductal Adenocarcinoma","kind":"Disorder","source_path":"kb/disorders/Pancreatic_Ductal_Adenocarcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pancreatic_Ductal_Adenocarcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pancreatic_Ductal_Adenocarcinoma.html#dataset-geo-gse111672"}],"context_names":["Pancreatic Ductal Adenocarcinoma"],"disease_names":["Pancreatic Ductal Adenocarcinoma"],"disease_name":"Pancreatic Ductal Adenocarcinoma","same_context_model_ids":["model:kb/disorders/Pancreatic_Ductal_Adenocarcinoma.yaml:Human PDAC Cell and Organoid RAS-Response Models"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a 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The stated observation is positional: in UV-sensitive syndrome cells the nonsense mutations sit upstream of the PGBD3 insertion in both alleles, whereas Cockayne cells carry mutations downstream of it or in exon 1. Forcing an upstream stop codon recovered mitochondrial membrane potential in Cockayne cells.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[16],"sample_count":16,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:3438","label":"ERCC6","display_label":"ERCC6","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/3438"}],"genes":["ERCC6"],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE111989","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE111989","reference_title":"Generation of splice switching oligonucleotides targeting the Cockayne syndrome group B gene product in order to change the diseased cell state","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The Cockayne syndrome group B (CSB) gene is one gene responsible for CS and also causes UV sensitive syndrome (UVSS), a disorder that causes mild symptoms.","explanation":"States the shared-gene, divergent-outcome relationship that this entry's knowledge gap is about, from a dataset that was designed around it."}],"notes":["Bears directly on the uvss_vs_cs_severity knowledge gap and is the reason that discussion now names the CSB-PGBD3 hypothesis. No linked PubMed record was found for this series."],"contexts":[{"id":"disorder:UV-Sensitive_Syndrome","name":"UV-Sensitive Syndrome","kind":"Disorder","source_path":"kb/disorders/UV-Sensitive_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/UV-Sensitive_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/UV-Sensitive_Syndrome.html#dataset-geo-gse111989"}],"context_names":["UV-Sensitive Syndrome"],"disease_names":["UV-Sensitive Syndrome"],"disease_name":"UV-Sensitive Syndrome","same_context_model_ids":["model:kb/disorders/UV-Sensitive_Syndrome.yaml:Isogenic TC-NER knockout human cell lines","model:kb/disorders/UV-Sensitive_Syndrome.yaml:Patient dermal fibroblast lines"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/UV-Sensitive_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/UV-Sensitive_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/UV-Sensitive_Syndrome.html#dataset-geo-gse111989"]},{"id":"dataset:geo:gse112086","accession":"geo:GSE112086","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE112086","title":"A transcriptional signature associated with non-Hodgkin lymphoma in the blood of patients with Q fever","alternate_titles":[],"description":"Coxiella burnetii, the agent causing Q fever, has been associated with B-cell non-Hodgkin lymphoma (NHL). To better clarify this link, we analysed the genetic transcriptomic profile of peripheral blood leukocytes from patients with C. burnetii infection to identify possible links to lymphoma. Microarray analyses revealed that 1189 genes were expressed differently (p <.001 and fold change ≥4) in whole blood of patients with C. burnetii infection compared to controls. In addition, 95 genes expressed in patients with non-Hodgkin lymphoma (NHL) and in patients with C. burnetii persistent infection have allowed us to establish the ‘C. burnetii-associated NHL signature’.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[21],"sample_count":21,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:31181104"],"publication_contexts":[{"context_id":"disorder:Q_Fever","publication":"PMID:31181104"}],"publication":"PMID:31181104","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/31181104","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Q Fever (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Q_Fever","name":"Q Fever","kind":"Disorder","source_path":"kb/disorders/Q_Fever.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Q_Fever.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Q_Fever.html#dataset-geo-gse112086"}],"context_names":["Q Fever"],"disease_names":["Q Fever"],"disease_name":"Q Fever","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association 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markers.","evidence":[{"reference":"geo:GSE112108","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE112108","reference_title":"Does early treatment of PKU patients with sapropterin dihydrochloride affect brain development?","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"RNAseq analyses revealed a number of significantly affected genes.","explanation":"Dataset summary confirms measurable transcriptional perturbations in treated developing brain cultures."},{"reference":"geo:GSE112108","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE112108","reference_title":"Does early treatment of PKU patients with sapropterin dihydrochloride affect brain development?","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Immunofluorescence for activated caspase-3 revealed an increased apoptosis rate.","explanation":"Summary links treatment exposure to increased apoptosis in the early developmental stage."}]}],"findings_text":["Early-stage sepiapterin exposure showed transcriptomic and cellular evidence of disturbed neural development, with increased apoptosis and altered glial/axonal markers."],"evidence":[{"reference":"geo:GSE112108","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE112108","reference_title":"Does early treatment of PKU patients with sapropterin dihydrochloride affect brain development?","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"RNAseq analyses revealed a number of significantly affected genes.","explanation":"Supports utility of this dataset for transcriptomic analysis of early PKU-treatment-relevant brain effects."},{"reference":"geo:GSE112108","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE112108","reference_title":"Does early treatment of PKU patients with sapropterin dihydrochloride affect brain development?","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Immunofluorescence for activated caspase-3 revealed an increased apoptosis rate.","explanation":"Summary links treatment exposure to increased apoptosis in the early developmental stage."}],"notes":[],"contexts":[{"id":"disorder:Phenylketonuria","name":"Phenylketonuria","kind":"Disorder","source_path":"kb/disorders/Phenylketonuria.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Phenylketonuria.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Phenylketonuria.html#dataset-geo-gse112108"}],"context_names":["Phenylketonuria"],"disease_names":["Phenylketonuria"],"disease_name":"Phenylketonuria","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association 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These include events previously characterized in the context of myotonic dystrophy type 1 and epithelial-to-mesenchymal transition, as well as splicing changes in genes related to proposed mechanisms of FECD pathogenesis.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[28],"sample_count":28,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:29966009"],"publication_contexts":[{"context_id":"disorder:Fuchs_Endothelial_Corneal_Dystrophy","publication":"PMID:29966009"}],"publication":"PMID:29966009","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/29966009","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Fuchs Endothelial Corneal Dystrophy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Fuchs_Endothelial_Corneal_Dystrophy","name":"Fuchs Endothelial Corneal Dystrophy","kind":"Disorder","source_path":"kb/disorders/Fuchs_Endothelial_Corneal_Dystrophy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fuchs_Endothelial_Corneal_Dystrophy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Fuchs_Endothelial_Corneal_Dystrophy.html#dataset-geo-gse112201"}],"context_names":["Fuchs Endothelial Corneal Dystrophy"],"disease_names":["Fuchs Endothelial Corneal Dystrophy"],"disease_name":"Fuchs Endothelial Corneal Dystrophy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Fuchs_Endothelial_Corneal_Dystrophy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fuchs_Endothelial_Corneal_Dystrophy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Fuchs_Endothelial_Corneal_Dystrophy.html#dataset-geo-gse112201"]},{"id":"dataset:geo:gse112278","accession":"geo:GSE112278","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE112278","title":"Blood transcriptome and clonal T cell correlates of response and nonresponse to eltrombopag therapy in a cohort of patients with chronic immune thrombocytopenia","alternate_titles":[],"description":"We evaluated the longitudinal effect of eltrombopag, a thrombopoietin receptor agonist, on gene expression in heavily pretreated patients with chronic immune thrombocytopenia (ITP) using blood transcriptome analysis on pretreatment, and following 1 week and 1 month of treatment samples. A strong stimulation of 208 eltrombopag-induced genes was identified in responders at 1-week time point. 90% of these genes are present in platelets, with GATA1, THPO, VIPAS39 and TGFB1 as top upstream regulators. Subsequently, despite a continued increase in platelet in responders, the eltrombopag-induced gene expression decreased at 1 month compared with the level at 1-week time point.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[46],"sample_count":46,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:31296576"],"publication_contexts":[{"context_id":"disorder:Immune_Thrombocytopenia","publication":"PMID:31296576"}],"publication":"PMID:31296576","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/31296576","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Immune Thrombocytopenia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Immune_Thrombocytopenia","name":"Immune Thrombocytopenia","kind":"Disorder","source_path":"kb/disorders/Immune_Thrombocytopenia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Immune_Thrombocytopenia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Immune_Thrombocytopenia.html#dataset-geo-gse112278"}],"context_names":["Immune Thrombocytopenia"],"disease_names":["Immune Thrombocytopenia"],"disease_name":"Immune Thrombocytopenia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Immune_Thrombocytopenia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Immune_Thrombocytopenia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Immune_Thrombocytopenia.html#dataset-geo-gse112278"]},{"id":"dataset:geo:gse1124","accession":"geo:GSE1124","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE1124","title":"Whole blood transcriptome of childhood malaria","alternate_titles":[],"description":"Whole-blood microarray profiling across asymptomatic infection, uncomplicated malaria, severe malarial anemia, cerebral malaria, and healthy controls in African children.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0000178","label":"blood","display_label":"blood","url":"http://purl.obolibrary.org/obo/UBERON_0000178"}],"sample_type_labels":["blood"],"sample_counts":[47],"sample_count":47,"conditions":["asymptomatic Plasmodium falciparum infection","uncomplicated malaria","severe malarial anemia","cerebral malaria","healthy controls"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["Affymetrix Human Genome U133A and U133B Arrays"],"platform":"Affymetrix Human Genome U133A and U133B Arrays","publications":["PMID:30638864"],"publication_contexts":[{"context_id":"disorder:Malaria","publication":"PMID:30638864"}],"publication":"PMID:30638864","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/30638864","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["GEO series metadata reports pooled whole-blood expression profiling across pediatric malaria severity strata."],"contexts":[{"id":"disorder:Malaria","name":"Malaria","kind":"Disorder","source_path":"kb/disorders/Malaria.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Malaria.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Malaria.html#dataset-geo-gse1124"}],"context_names":["Malaria"],"disease_names":["Malaria"],"disease_name":"Malaria","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Malaria.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Malaria.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Malaria.html#dataset-geo-gse1124"]},{"id":"dataset:geo:gse112958","accession":"geo:GSE112958","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE112958","title":"Transcriptional responses in whole blood of healthy adult volunteers experimentally challenged with S. 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Typhi Quailes strain challenge, at day 7 in suspected enteric fever participants, and at the diagnostic endpoint in typhoid fever participants.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[178],"sample_count":178,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:31468702"],"publication_contexts":[{"context_id":"disorder:Typhoid_Fever","publication":"PMID:31468702"}],"publication":"PMID:31468702","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/31468702","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Typhoid Fever; accession and metadata verified against NCBI E-utilities on 2026-09-25. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Typhoid_Fever","name":"Typhoid Fever","kind":"Disorder","source_path":"kb/disorders/Typhoid_Fever.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Typhoid_Fever.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Typhoid_Fever.html#dataset-geo-gse112958"}],"context_names":["Typhoid Fever"],"disease_names":["Typhoid Fever"],"disease_name":"Typhoid Fever","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Typhoid_Fever.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Typhoid_Fever.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Typhoid_Fever.html#dataset-geo-gse112958"]},{"id":"dataset:geo:gse113251","accession":"geo:GSE113251","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE113251","title":"Deletion of Nkx2-5 in trabecular myocardium reveals the developmental origins of pathological heterogeneity associated with ventricular non-compaction cardiomyopathy","alternate_titles":[],"description":"Public LVNC transcriptomic dataset used alongside GSE71912 for differential expression, co-expression, and hub-gene analysis.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":["left ventricular noncompaction cardiomyopathy"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40618167"],"publication_contexts":[{"context_id":"disorder:Left_Ventricular_Noncompaction","publication":"PMID:40618167"}],"publication":"PMID:40618167","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40618167","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:40618167","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40618167","reference_title":"Role of Col1a2 and Postn in left ventricular noncompaction cardiomyopathy.","supports":"SUPPORT","evidence_source":"COMPUTATIONAL","snippet":"The datasets GSE71912 and GSE113251 of left ventricular noncompaction cardiomyopathy were downloaded from the gene expression omnibus (GEO) database generated from GPL13912 and GPL11002 platforms.","explanation":"Supports GSE113251 as a second public LVNC dataset used in integrated computational analyses."}],"notes":[],"contexts":[{"id":"disorder:Left_Ventricular_Noncompaction","name":"Left ventricular noncompaction","kind":"Disorder","source_path":"kb/disorders/Left_Ventricular_Noncompaction.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Left_Ventricular_Noncompaction.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Left_ventricular_noncompaction.html#dataset-geo-gse113251"}],"context_names":["Left ventricular noncompaction"],"disease_names":["Left ventricular noncompaction"],"disease_name":"Left ventricular noncompaction","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Left_Ventricular_Noncompaction.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Left_Ventricular_Noncompaction.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Left_ventricular_noncompaction.html#dataset-geo-gse113251"]},{"id":"dataset:geo:gse113300","accession":"geo:GSE113300","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE113300","title":"Differential expression of miRNAs in a cellular model of MELAS.","alternate_titles":[],"description":"Small-RNA sequencing of a transmitochondrial cybrid model homoplasmic for m.3243A>G, identifying 246 differentially expressed miRNAs whose predicted targets fall in muscle, nervous-system, and cardiac developmental pathways.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["A candidate source for circulating-biomarker work, since miRNAs survive in plasma where transcriptomes do not. Two limits are worth stating: the model is 100% mutant cybrid rather than patient tissue, and the target pathways are computationally predicted. No linked publication in the repository record."],"contexts":[{"id":"disorder:MELAS_Syndrome","name":"MELAS Syndrome","kind":"Disorder","source_path":"kb/disorders/MELAS_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MELAS_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/MELAS_Syndrome.html#dataset-geo-gse113300"}],"context_names":["MELAS Syndrome"],"disease_names":["MELAS Syndrome"],"disease_name":"MELAS Syndrome","same_context_model_ids":["model:kb/disorders/MELAS_Syndrome.yaml:m.3243A>G patient iPSC-derived neurons"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/MELAS_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MELAS_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/MELAS_Syndrome.html#dataset-geo-gse113300"]},{"id":"dataset:geo:gse113333","accession":"geo:GSE113333","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE113333","title":"Human intestinal biopsy gene expression after infection with Salmonella enterica serovar Typhi","alternate_titles":[],"description":"Bulk RNA-seq of healthy human intestinal biopsy tissue used to measure human and bacterial gene expression changes after S. Typhi colonization.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[13],"sample_count":13,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:29735417"],"publication_contexts":[{"context_id":"disorder:Typhoid_Fever","publication":"PMID:29735417"}],"publication":"PMID:29735417","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/29735417","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Typhoid Fever; accession and metadata verified against NCBI E-utilities on 2026-09-25. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Typhoid_Fever","name":"Typhoid Fever","kind":"Disorder","source_path":"kb/disorders/Typhoid_Fever.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Typhoid_Fever.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Typhoid_Fever.html#dataset-geo-gse113333"}],"context_names":["Typhoid Fever"],"disease_names":["Typhoid Fever"],"disease_name":"Typhoid Fever","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Typhoid_Fever.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Typhoid_Fever.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Typhoid_Fever.html#dataset-geo-gse113333"]},{"id":"dataset:geo:gse113496","accession":"geo:GSE113496","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE113496","title":"Genetic defects affecting the development of severe Buruli Ulcer","alternate_titles":[],"description":"Buruli ulcer (BU) is a tropical infectious disease caused by Mycobacterium ulcerans. BU causes profound skin ulcerations and eventually bone infections. Life-long functional sequelae are observed in more than 20% of patients, most of whom are children. Several observations, in particular the large variability in the clinical severity of the disease after infection, suggested the role of human genetic factors in the development of BU. Here, we report two children with severe BU, born of consanguineous parents. The deep genetic exploration of this family led to the identification of a small deletion on chromosome 8 in both patients.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[7],"sample_count":7,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:29708969"],"publication_contexts":[{"context_id":"disorder:Buruli_Ulcer","publication":"PMID:29708969"}],"publication":"PMID:29708969","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/29708969","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Buruli ulcer (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Buruli_Ulcer","name":"Buruli ulcer","kind":"Disorder","source_path":"kb/disorders/Buruli_Ulcer.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Buruli_Ulcer.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Buruli_ulcer.html#dataset-geo-gse113496"}],"context_names":["Buruli ulcer"],"disease_names":["Buruli ulcer"],"disease_name":"Buruli ulcer","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Buruli_Ulcer.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Buruli_Ulcer.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Buruli_ulcer.html#dataset-geo-gse113496"]},{"id":"dataset:geo:gse113871","accession":"geo:GSE113871","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE113871","title":"Cardiac organoid model of human myocardial infarction","alternate_titles":[],"description":"RNA-seq of human cardiac organoids carried through the oxygen-gradient infarction protocol versus control organoids. The transcriptomic arm of the infarct-organoid model curated in this entry's experimental_models block.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:32284552"],"publication_contexts":[{"context_id":"disorder:Myocardial_Infarction","publication":"PMID:32284552"}],"publication":"PMID:32284552","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32284552","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE113871","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE113871","reference_title":null,"supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"we leveraged the diffusion limitation in 3D microtissues to recreate the nutrient diffusion gradient across infarcted hearts (i.e., infarct-border-remote zones) in human cardiac organoids to induce cardiac organotypic response to infarction","explanation":"The repository's own summary states the gradient-based infarction protocol whose transcriptomes this series holds."}],"notes":["Deposited by PMID:32284552, the source of the oxygen-gradient cardiac infarct organoid in experimental_models. Title copied from GEO; accession verified against the cached GEO record."],"contexts":[{"id":"disorder:Myocardial_Infarction","name":"Myocardial Infarction","kind":"Disorder","source_path":"kb/disorders/Myocardial_Infarction.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myocardial_Infarction.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Myocardial_Infarction.html#dataset-geo-gse113871"}],"context_names":["Myocardial Infarction"],"disease_names":["Myocardial Infarction"],"disease_name":"Myocardial Infarction","same_context_model_ids":["model:kb/disorders/Myocardial_Infarction.yaml:Bioelectronically instrumented heart-on-a-chip under acute hypoxia","model:kb/disorders/Myocardial_Infarction.yaml:Epicardial-myocardial heart-on-a-chip model of ischemia-reperfusion injury","model:kb/disorders/Myocardial_Infarction.yaml:Human cardiac infarct organoid with an internal oxygen-diffusion gradient","model:kb/disorders/Myocardial_Infarction.yaml:Human heart-on-a-chip ischemia-reperfusion assay with endothelial extracellular vesicle rescue","model:kb/disorders/Myocardial_Infarction.yaml:Myocardial infarct border-zone-on-a-chip"],"candidate_model_ids":["model:kb/disorders/Myocardial_Infarction.yaml:Human cardiac infarct organoid with an internal oxygen-diffusion gradient"],"association_basis":"Same publication as a NAM (candidate)","nam_disease_context":"Same publication as a NAM (candidate)","source_paths":["kb/disorders/Myocardial_Infarction.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myocardial_Infarction.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Myocardial_Infarction.html#dataset-geo-gse113871"]},{"id":"dataset:geo:gse114033","accession":"geo:GSE114033","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE114033","title":"Transcriptional responses in whole blood of healthy adult volunteers experimentally challenged with S. Paratyphi","alternate_titles":[],"description":"This studies describes the transcriptional response in whole blood derived from healthy adult volunteers experimentally infected with S. Paratyphi A. Samples were collected at pre-challenge baseline (Group: CTRL), at day 7 after challenge in those participants who stayed well over 14 days following challenge (Group: suspected Enteric Fever - sEF). Participants who developed signs of enteric fever were sampled at the time of inititiation of antibiotics (Group: EF).In this group diagnosis was confirmed by blood culture positive for S. Paratyphi (SPT). Antibiotic therapy commenced at time of diagnosis or at day 14 after challenge in those who did not develop symptoms.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[75],"sample_count":75,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:31468702"],"publication_contexts":[{"context_id":"disorder:Paratyphoid_Fever","publication":"PMID:31468702"}],"publication":"PMID:31468702","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/31468702","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Paratyphoid Fever (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Paratyphoid_Fever","name":"Paratyphoid Fever","kind":"Disorder","source_path":"kb/disorders/Paratyphoid_Fever.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Paratyphoid_Fever.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Paratyphoid_Fever.html#dataset-geo-gse114033"}],"context_names":["Paratyphoid Fever"],"disease_names":["Paratyphoid Fever"],"disease_name":"Paratyphoid Fever","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Paratyphoid_Fever.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Paratyphoid_Fever.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Paratyphoid_Fever.html#dataset-geo-gse114033"]},{"id":"dataset:geo:gse114783","accession":"geo:GSE114783","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE114783","title":"Microarray gene expression from hepatitis B virus infection to hepatocellular carcinoma","alternate_titles":[],"description":"Background: The pathogenesis of hepatitis B virus (HBV)-caused hepatocellular carcinoma (HCC) is complex and not fully understood. In clinical, the effective prevention and treatment of HCC rely on the accurate diagnosis. We developed a biology network approach to investigate the potential mechanisms and biomarkers of each stages from HBV infection to HCC. Methods Global gene profiling of healthy individuals (HC), HBV carriers (HBVC), chronic hepatitis B patients (CHB), liver cirrhosis (LC) and HCC was analyzed by gene array. Differentially expressed genes (DEG) were found by RVM (Random variance model) corrective ANOVA and STC (Series Test of Cluster) analysis.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[36],"sample_count":36,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:30925583"],"publication_contexts":[{"context_id":"disorder:Hepatitis_B","publication":"PMID:30925583"}],"publication":"PMID:30925583","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/30925583","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Hepatitis B (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Hepatitis_B","name":"Hepatitis B","kind":"Disorder","source_path":"kb/disorders/Hepatitis_B.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatitis_B.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hepatitis_B.html#dataset-geo-gse114783"}],"context_names":["Hepatitis B"],"disease_names":["Hepatitis B"],"disease_name":"Hepatitis B","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hepatitis_B.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatitis_B.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hepatitis_B.html#dataset-geo-gse114783"]},{"id":"dataset:geo:gse115031","accession":"geo:GSE115031","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE115031","title":"Cardiac organoid model of human myocardial infarction (batch2)","alternate_titles":[],"description":"Second donor batch of the cardiac infarct organoid RNA-seq, used in the source publication to test whether the infarct hallmarks survive a change of hiPSC genetic background.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:32284552"],"publication_contexts":[{"context_id":"disorder:Myocardial_Infarction","publication":"PMID:32284552"}],"publication":"PMID:32284552","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32284552","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Deposited by PMID:32284552 as the Donor B replication of GSE113871. 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Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Rhinovirus_Infection","name":"Rhinovirus Infection","kind":"Disorder","source_path":"kb/disorders/Rhinovirus_Infection.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rhinovirus_Infection.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Rhinovirus_Infection.html#dataset-geo-gse118875"}],"context_names":["Rhinovirus Infection"],"disease_names":["Rhinovirus Infection"],"disease_name":"Rhinovirus Infection","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Rhinovirus_Infection.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rhinovirus_Infection.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Rhinovirus_Infection.html#dataset-geo-gse118875"]},{"id":"dataset:geo:gse11911","accession":"geo:GSE11911","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE11911","title":"Gene expression profiling of experimental asthma reveals a possible role of paraoxonase-1 in asthma","alternate_titles":[],"description":"Gene expression from lung tissue of ovalbumin-sensitized and challenged BALB/c mice modeling allergic airway inflammation.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[{"id":"UBERON:0002048","label":"lung","display_label":"lung","url":"http://purl.obolibrary.org/obo/UBERON_0002048"}],"sample_type_labels":["lung"],"sample_counts":[],"sample_count":null,"conditions":["OVA-sensitized and challenged","control"],"exposure_terms":[{"id":"ECTO:0000726","label":"exposure to allergen","display_label":"ovalbumin allergen challenge","url":"http://purl.obolibrary.org/obo/ECTO_0000726"}],"exposures":["exposure to allergen"],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Classic murine allergic airway inflammation model"],"contexts":[{"id":"disorder:Asthma","name":"Asthma","kind":"Disorder","source_path":"kb/disorders/Asthma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Asthma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Asthma.html#dataset-geo-gse11911"}],"context_names":["Asthma"],"disease_names":["Asthma"],"disease_name":"Asthma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Asthma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Asthma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Asthma.html#dataset-geo-gse11911"]},{"id":"dataset:geo:gse119117","accession":"geo:GSE119117","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE119117","title":"Longitudinal transcriptomic characterization of the immune response to acute hepatitis C virus infection","alternate_titles":[],"description":"Most individuals exposed to hepatitis C virus (HCV) become persistently infected while a minority spontaneously eliminate the virus. Although early immune events influence infection outcome, the cellular composition, molecular effectors, and timeframe of the host response active shortly after viral exposure remain incompletely understood. Employing specimens collected from people who inject drugs (PWID) with high risk of HCV exposure, we utilized RNA-Seq to characterize immune function in peripheral blood before, during, and after acute HCV infection resulting in spontaneous resolution.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[53],"sample_count":53,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:30222771"],"publication_contexts":[{"context_id":"disorder:Hepatitis_C","publication":"PMID:30222771"}],"publication":"PMID:30222771","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/30222771","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Hepatitis C (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Hepatitis_C","name":"Hepatitis C","kind":"Disorder","source_path":"kb/disorders/Hepatitis_C.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatitis_C.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hepatitis_C.html#dataset-geo-gse119117"}],"context_names":["Hepatitis C"],"disease_names":["Hepatitis C"],"disease_name":"Hepatitis C","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hepatitis_C.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatitis_C.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hepatitis_C.html#dataset-geo-gse119117"]},{"id":"dataset:geo:gse119136","accession":"geo:GSE119136","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE119136","title":"Defining the Nasal Transcriptome in Granulomatosis with Polyangiitis","alternate_titles":[],"description":"Objectives: To determine whether disease processes related to granulomatosis with polyangiitis (GPA) are reflected in gene expression profiles of nasal mucosa. Methods: Nasal brushings of the inferior turbinate were obtained from 32 patients with GPA (10 with active nasal disease, 13 with prior nasal disease, 9 with no history of nasal disease) and a composite comparator group with and without inflammatory nasal disease (12 healthy people, 15 with sarcoidosis, 8 with allergic rhinitis). Differential gene expression was assessed between subgroups of GPA and comparators.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[76],"sample_count":76,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:25939343"],"publication_contexts":[{"context_id":"disorder:Granulomatosis_with_Polyangiitis","publication":"PMID:25939343"}],"publication":"PMID:25939343","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/25939343","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Granulomatosis with Polyangiitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Granulomatosis_with_Polyangiitis","name":"Granulomatosis with Polyangiitis","kind":"Disorder","source_path":"kb/disorders/Granulomatosis_with_Polyangiitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Granulomatosis_with_Polyangiitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Granulomatosis_with_Polyangiitis.html#dataset-geo-gse119136"}],"context_names":["Granulomatosis with Polyangiitis"],"disease_names":["Granulomatosis with Polyangiitis"],"disease_name":"Granulomatosis with Polyangiitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Granulomatosis_with_Polyangiitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Granulomatosis_with_Polyangiitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Granulomatosis_with_Polyangiitis.html#dataset-geo-gse119136"]},{"id":"dataset:geo:gse119322","accession":"geo:GSE119322","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE119322","title":"Characteristics of impaired dendritic cell function in patients with hepatitis B virus infection","alternate_titles":[],"description":"Dendritic cells are antigen-presenting cells with a central role in host immune response. This study analyzed gene expression and dendritic cell function in hepatitis B virus (HBV) patients and functions impaired due to HBV, and identified the genes related to these functions. Peripheral blood mononuclear cells from 23 HBV patients and 9 healthy controls were utilized. Mononuclear cells were isolated from side-scatter and forward-scatter gating using fluorescence-activated cell sorting (FACS), the lineage-negative HLA-DR-positive fraction was extracted, and was further divided into CD123-positive plasmacytoid DCs (pDCs) and CD11c-positive myeloid DCs (mDCs).","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[32],"sample_count":32,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:30938456"],"publication_contexts":[{"context_id":"disorder:Hepatitis_B","publication":"PMID:30938456"}],"publication":"PMID:30938456","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/30938456","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Hepatitis B (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Hepatitis_B","name":"Hepatitis B","kind":"Disorder","source_path":"kb/disorders/Hepatitis_B.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatitis_B.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hepatitis_B.html#dataset-geo-gse119322"}],"context_names":["Hepatitis B"],"disease_names":["Hepatitis B"],"disease_name":"Hepatitis B","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hepatitis_B.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatitis_B.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hepatitis_B.html#dataset-geo-gse119322"]},{"id":"dataset:geo:gse119376","accession":"geo:GSE119376","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE119376","title":"Adverse Events of anti-EGFR Therapy are Triggered by Hair Eruption and Commensal Skin Microbiota","alternate_titles":[],"description":"Expression profiling of primary human epidermal keratinocytes under EGFR inhibition, describing barrier dysfunction and chronic folliculitis-related inflammatory programs.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":["keratinocytes, EGFR inhibition","keratinocytes, control"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE119376","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE119376","reference_title":"Adverse Events of anti-EGFR Therapy are Triggered by Hair Eruption and Commensal Skin Microbiota","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"In the absence of EGFR, opening of the follicular ostia during hair eruption allows invasion of commensal microbiota aggravating barrier disruption and initiating an additional Th1 and Th17 response.","explanation":"Supports EGFR-perturbation-associated follicular barrier and immune dysregulation mechanisms."},{"reference":"GEO:GSE119376","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE119376","reference_title":"Adverse Events of anti-EGFR Therapy are Triggered by Hair Eruption and Commensal Skin Microbiota","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Chronic folliculitis leads to Staphylococcus aureus dominated dysbiosis, further exacerbating inflammation and expanding barrier defects.","explanation":"Directly supports chronic folliculitis-associated dysbiosis and inflammatory amplification."}],"notes":[],"contexts":[{"id":"disorder:Folliculitis","name":"Folliculitis","kind":"Disorder","source_path":"kb/disorders/Folliculitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Folliculitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Folliculitis.html#dataset-geo-gse119376"}],"context_names":["Folliculitis"],"disease_names":["Folliculitis"],"disease_name":"Folliculitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Folliculitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Folliculitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Folliculitis.html#dataset-geo-gse119376"]},{"id":"dataset:geo:gse119622","accession":"geo:GSE119622","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE119622","title":"S. flexneri transcriptome in Henle-407 cells","alternate_titles":[],"description":"Gene expression analysis of Shigella flexneri during infection of human intestinal epithelial cells (Henle-407). Tracks bacterial and host transcriptional changes during acute infection providing molecular insights into pathogenic mechanisms.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"Homo sapiens","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"CL:0002669","label":"intestinal epithelial cell","display_label":"intestinal epithelial cell","url":"http://purl.obolibrary.org/obo/CL_0002669"}],"sample_type_labels":["intestinal epithelial cell"],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["No associated publication found in GEO records"],"contexts":[{"id":"disorder:Shigellosis","name":"Shigellosis","kind":"Disorder","source_path":"kb/disorders/Shigellosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Shigellosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Shigellosis.html#dataset-geo-gse119622"}],"context_names":["Shigellosis"],"disease_names":["Shigellosis"],"disease_name":"Shigellosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Shigellosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Shigellosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Shigellosis.html#dataset-geo-gse119622"]},{"id":"dataset:geo:gse119911","accession":"geo:GSE119911","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE119911","title":"Comprehensive transcriptomic profiles of non-small cell lung cancer by single-cell RNA-seq","alternate_titles":[],"description":"Single-cell RNA sequencing profiling over 9,000 individual cells from tumor and adjacent normal tissues of 20 patients with stage I-IV NSCLC using modified STRT-seq technique.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0002048","label":"lung","display_label":"lung","url":"http://purl.obolibrary.org/obo/UBERON_0002048"}],"sample_type_labels":["lung"],"sample_counts":[106],"sample_count":106,"conditions":["NSCLC tumor tissue","adjacent normal tissue"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Characterizes inter-patient and intra-tumor heterogeneity including epithelial, stromal, and immune cell compartments. Useful for understanding cancer progression and therapeutic strategies"],"contexts":[{"id":"disorder:Non-Small_Cell_Lung_Cancer","name":"Non-Small Cell Lung Cancer","kind":"Disorder","source_path":"kb/disorders/Non-Small_Cell_Lung_Cancer.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Non-Small_Cell_Lung_Cancer.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Non-Small_Cell_Lung_Cancer.html#dataset-geo-gse119911"}],"context_names":["Non-Small Cell Lung Cancer"],"disease_names":["Non-Small Cell Lung Cancer"],"disease_name":"Non-Small Cell Lung Cancer","same_context_model_ids":["model:kb/disorders/Non-Small_Cell_Lung_Cancer.yaml:Human orthotopic NSCLC lung organ-on-chip (Wyss Institute)"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Non-Small_Cell_Lung_Cancer.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Non-Small_Cell_Lung_Cancer.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Non-Small_Cell_Lung_Cancer.html#dataset-geo-gse119911"]},{"id":"dataset:geo:gse120225","accession":"geo:GSE120225","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE120225","title":"Channelopathy pathogenesis in a human neural cell model of Angelman Syndrome","alternate_titles":[],"description":"RNA-seq dataset from human induced neurons and 3D cortical organoids derived from Angelman patient iPSCs and UBE3A-knockout hESC lines, used to study network hyperexcitability mechanisms.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":["Angelman syndrome iPSC-derived neural model","UBE3A-knockout hESC-derived neural model","control neural model"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE120225","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE120225","reference_title":"Channelopathy pathogenesis in a human neural cell model of Angelman Syndrome","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Here, by utilizing human induced neurons and 3D cortical organoids derived from AS patient iPSCs and CRISPR-Cas9 mediated UBE3A KO hESCs, we uncovered a novel role of UBE3A in suppressing neuronal hyperexcitability via ubiquitin-mediated degradation of BK channels.","explanation":"Supports relevance for human-cell-model mechanisms linking UBE3A loss to neuronal hyperexcitability."}],"notes":[],"contexts":[{"id":"disorder:Angelman_Syndrome","name":"Angelman Syndrome","kind":"Disorder","source_path":"kb/disorders/Angelman_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Angelman_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Angelman_Syndrome.html#dataset-geo-gse120225"}],"context_names":["Angelman Syndrome"],"disease_names":["Angelman Syndrome"],"disease_name":"Angelman Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Angelman_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Angelman_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Angelman_Syndrome.html#dataset-geo-gse120225"]},{"id":"dataset:geo:gse121010","accession":"geo:GSE121010","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE121010","title":"Comparison of cortical grey matter from Rasmussen Encephalitis patients and age-matched epileptic controls","alternate_titles":[],"description":"We performed whole-genome transcriptome analysis of Rasmussen Encephalitis of the early disease stages for an overview of differentially expressed pathways leading to widespread neuroinflammation and degeneration.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene 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Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Rasmussen_Encephalitis","name":"Rasmussen Encephalitis","kind":"Disorder","source_path":"kb/disorders/Rasmussen_Encephalitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rasmussen_Encephalitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Rasmussen_Encephalitis.html#dataset-geo-gse121010"}],"context_names":["Rasmussen Encephalitis"],"disease_names":["Rasmussen Encephalitis"],"disease_name":"Rasmussen Encephalitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Rasmussen_Encephalitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rasmussen_Encephalitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Rasmussen_Encephalitis.html#dataset-geo-gse121010"]},{"id":"dataset:geo:gse121385","accession":"geo:GSE121385","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE121385","title":"RNA-Sequencing data of Varicella Zoster Virus (VZV)-infected human dermal fibroblasts (HDF)","alternate_titles":[],"description":"RNA-seq comparing host transcriptomic responses in human dermal fibroblasts infected with clinical versus vaccine (Oka) VZV strains. Identifies differential immune pathway activation between wild-type and attenuated virus.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"CL:0002551","label":"fibroblast of dermis","display_label":"fibroblast of dermis","url":"http://purl.obolibrary.org/obo/CL_0002551"}],"sample_type_labels":["fibroblast of dermis"],"sample_counts":[6],"sample_count":6,"conditions":["clinical VZV strain-infected","vaccine (Oka) VZV strain-infected","mock-infected controls"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["Illumina HiSeq 2500"],"platform":"Illumina HiSeq 2500","publications":["PMID:31658769"],"publication_contexts":[{"context_id":"disorder:Chickenpox","publication":"PMID:31658769"}],"publication":"PMID:31658769","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/31658769","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Relevant to understanding differential host responses to wild-type vs vaccine VZV strains, informing vaccine mechanism of action."],"contexts":[{"id":"disorder:Chickenpox","name":"Chickenpox","kind":"Disorder","source_path":"kb/disorders/Chickenpox.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chickenpox.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chickenpox.html#dataset-geo-gse121385"}],"context_names":["Chickenpox"],"disease_names":["Chickenpox"],"disease_name":"Chickenpox","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chickenpox.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chickenpox.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chickenpox.html#dataset-geo-gse121385"]},{"id":"dataset:geo:gse121412","accession":"geo:GSE121412","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE121412","title":"Epigenetic intersection of BDNF Val66Met genotype with premenstrual dysphoric disorder transcriptome in a cross-species model of estradiol add-back","alternate_titles":[],"description":"Ovariectomized BDNF Val66Met mice, a model that is genetically susceptible to stress, exhibited anxiety- and depression-like behavior when treated with estradiol when compared to wild type mice. Comparing ventral hippocampus of these mice with lymphoblastoid cell line cultures of control women and women with prementrual dysphoric disorder revealed common epigenetic biomarkers that transcend species and cell-type.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[10],"sample_count":10,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:30356121"],"publication_contexts":[{"context_id":"disorder:Premenstrual_Dysphoric_Disorder","publication":"PMID:30356121"}],"publication":"PMID:30356121","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/30356121","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Premenstrual Dysphoric Disorder (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Premenstrual_Dysphoric_Disorder","name":"Premenstrual Dysphoric Disorder","kind":"Disorder","source_path":"kb/disorders/Premenstrual_Dysphoric_Disorder.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Premenstrual_Dysphoric_Disorder.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Premenstrual_Dysphoric_Disorder.html#dataset-geo-gse121412"}],"context_names":["Premenstrual Dysphoric Disorder"],"disease_names":["Premenstrual Dysphoric Disorder"],"disease_name":"Premenstrual Dysphoric Disorder","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Premenstrual_Dysphoric_Disorder.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Premenstrual_Dysphoric_Disorder.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Premenstrual_Dysphoric_Disorder.html#dataset-geo-gse121412"]},{"id":"dataset:geo:gse121600","accession":"geo:GSE121600","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE121600","title":"Single-cell RNA-seq reveals novel cell differentiation dynamics during human airway epithelium regeneration","alternate_titles":[],"description":"Single-cell transcriptomic characterization of multiciliated, goblet, secretory, and basal cells during human airway epithelium regeneration. Includes nasal brushing and turbinate samples, with cross-species validation. Relevant to understanding mucociliary differentiation dynamics disrupted in ENS.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"CL:0002480","label":"nasal mucosa goblet cell","display_label":"nasal mucosa goblet cell","url":"http://purl.obolibrary.org/obo/CL_0002480"}],"sample_type_labels":["nasal mucosa goblet cell"],"sample_counts":[22],"sample_count":22,"conditions":["human airway epithelium regeneration","fresh nasal brushing"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:31558434"],"publication_contexts":[{"context_id":"disorder:Empty_Nose_Syndrome","publication":"PMID:31558434"}],"publication":"PMID:31558434","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/31558434","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Characterizes goblet cell and multiciliated cell differentiation trajectories relevant to the mucociliary dysfunction seen in ENS."],"contexts":[{"id":"disorder:Empty_Nose_Syndrome","name":"Empty Nose Syndrome","kind":"Disorder","source_path":"kb/disorders/Empty_Nose_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Empty_Nose_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Empty_Nose_Syndrome.html#dataset-geo-gse121600"}],"context_names":["Empty Nose Syndrome"],"disease_names":["Empty Nose Syndrome"],"disease_name":"Empty Nose Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Empty_Nose_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Empty_Nose_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Empty_Nose_Syndrome.html#dataset-geo-gse121600"]},{"id":"dataset:geo:gse121867","accession":"geo:GSE121867","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE121867","title":"RNA Sequencing of CSF Samples from Patients with Intraventricular Hemorrhage and Neural Tube Defects","alternate_titles":[],"description":"CSF transcriptomes from human patients with intraventricular haemorrhage and with neural tube defects — the two acquired/malformation routes curated as the post-haemorrhagic and Chiari II-associated subtypes here.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[70],"sample_count":70,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:30951672"],"publication_contexts":[{"context_id":"disorder:Congenital_Hydrocephalus","publication":"PMID:30951672"}],"publication":"PMID:30951672","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/30951672","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Discovered with just discover-datasets (DIRECT) and resolved with just verify-datasets. Relevance triaged manually: both patient groups map onto curated subtypes of this entry."],"contexts":[{"id":"disorder:Congenital_Hydrocephalus","name":"Congenital Hydrocephalus","kind":"Disorder","source_path":"kb/disorders/Congenital_Hydrocephalus.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Congenital_Hydrocephalus.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Congenital_Hydrocephalus.html#dataset-geo-gse121867"}],"context_names":["Congenital Hydrocephalus"],"disease_names":["Congenital Hydrocephalus"],"disease_name":"Congenital Hydrocephalus","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Congenital_Hydrocephalus.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Congenital_Hydrocephalus.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Congenital_Hydrocephalus.html#dataset-geo-gse121867"]},{"id":"dataset:geo:gse121960","accession":"geo:GSE121960","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE121960","title":"Survival of cells with deregulated MYC requires UVSSA-dependent regulation of RNAPII dynamics","alternate_titles":[],"description":"UVSSA knockdown in MYC-activated cancer cells, measuring RNA polymerase II dynamics. The disease framing is oncology, not this syndrome, but the biology measured is UVSSA-dependent handling of RNA polymerase II, which is the mechanism node this entry is built on.","alternate_descriptions":[],"data_types":["CHIP_SEQ"],"data_type_labels":["Chromatin immunoprecipitation sequencing"],"data_type_label":"Chromatin immunoprecipitation sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[16],"sample_count":16,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:29304","label":"UVSSA","display_label":"UVSSA","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/29304"}],"genes":["UVSSA"],"platforms":[],"platform":null,"publications":["PMID:33404608"],"publication_contexts":[{"context_id":"disorder:UV-Sensitive_Syndrome","publication":"PMID:33404608"}],"publication":"PMID:33404608","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/33404608","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE121960","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE121960","reference_title":"Survival of cells with deregulated MYC requires UVSSA-dependent regulation of RNAPII dynamics","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Based on previously conducted genome-wide screenings we identified UVSSA, a gene involved in transcription-coupled repair whose knockdown decreased cell viability when combined with MYC activation.","explanation":"Confirms the gene identity and its transcription-coupled repair role. Graded INDIRECT because the experiment is about oncogene-driven transcription stress rather than this disease."}],"notes":["Included as a gene-matched resource under one of the three causal genes, with the caveat stated: it measures the pathway, not the syndrome. A curator reading it for disease phenotype rather than for UVSSA-RNAPII biology would be misreading it."],"contexts":[{"id":"disorder:UV-Sensitive_Syndrome","name":"UV-Sensitive Syndrome","kind":"Disorder","source_path":"kb/disorders/UV-Sensitive_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/UV-Sensitive_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/UV-Sensitive_Syndrome.html#dataset-geo-gse121960"}],"context_names":["UV-Sensitive Syndrome"],"disease_names":["UV-Sensitive Syndrome"],"disease_name":"UV-Sensitive Syndrome","same_context_model_ids":["model:kb/disorders/UV-Sensitive_Syndrome.yaml:Isogenic TC-NER knockout human cell lines","model:kb/disorders/UV-Sensitive_Syndrome.yaml:Patient dermal fibroblast lines"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/UV-Sensitive_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/UV-Sensitive_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/UV-Sensitive_Syndrome.html#dataset-geo-gse121960"]},{"id":"dataset:geo:gse122476","accession":"geo:GSE122476","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE122476","title":"Circulating CD1c+ myeloid dendritic cells are precursors to Langerhans cell histiocytosis (LCH) lesion CD1a+CD207+cells","alternate_titles":[],"description":"Expression data from LCH lesion subpopulations and healthy donors' peripheral blood specimens Langerhans cell histiocytosis (LCH) is a myeloproliferative disorder that is characterized by the inflammatory lesions with pathogenic CD1a+CD207+ dendritic cells (DCs). BRAFV600E and other somatic activating MAPK gene mutations have been identified in differentiating bone marrow and blood myeloid cells, but the origin of the LCH lesion CD1a+CD207+DCs and mechanisms of lesion formation remain incompletely defined.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[57],"sample_count":57,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:31899802"],"publication_contexts":[{"context_id":"disorder:Langerhans_Cell_Histiocytosis","publication":"PMID:31899802"}],"publication":"PMID:31899802","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/31899802","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Langerhans Cell Histiocytosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Langerhans_Cell_Histiocytosis","name":"Langerhans Cell Histiocytosis","kind":"Disorder","source_path":"kb/disorders/Langerhans_Cell_Histiocytosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Langerhans_Cell_Histiocytosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Langerhans_Cell_Histiocytosis.html#dataset-geo-gse122476"}],"context_names":["Langerhans Cell Histiocytosis"],"disease_names":["Langerhans Cell Histiocytosis"],"disease_name":"Langerhans Cell Histiocytosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Langerhans_Cell_Histiocytosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Langerhans_Cell_Histiocytosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Langerhans_Cell_Histiocytosis.html#dataset-geo-gse122476"]},{"id":"dataset:geo:gse122584","accession":"geo:GSE122584","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE122584","title":"Phenotypic cooperation of a KCNQ2 exon 7 partial duplication and compound copy number variations in genes associated to a severe epileptic and neurodevelopmental delay","alternate_titles":[],"description":"SNP-array copy-number profiling of a family in which a boy with neonatal-onset epileptic encephalopathy carries a partial duplication of KCNQ2 exon 7 together with additional copy-number variants. A single-family genomic record rather than a cohort, so it speaks to variant architecture in one severe case, not to the population genetics of the disorder.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[4],"sample_count":4,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:6296","label":"KCNQ2","display_label":"KCNQ2","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/6296"}],"genes":["KCNQ2"],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Found by a targeted GEO DataSets title search for KCNQ2; accession verified against NCBI E-utilities on 2026-08-27. Title, sample count, and organism are GEO's own values. data_type is deliberately omitted: GEO types the assay \"Genome variation profiling by SNP array\" and DatasetTypeEnum has no array-CGH/SNP-array value - MICROARRAY means expression array and WGS/WES mean sequencing, so any of them would misstate the assay. GEO lists no linked publication for this series."],"contexts":[{"id":"disorder:KCNQ2_Developmental_and_Epileptic_Encephalopathy","name":"KCNQ2 Developmental and Epileptic Encephalopathy","kind":"Disorder","source_path":"kb/disorders/KCNQ2_Developmental_and_Epileptic_Encephalopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/KCNQ2_Developmental_and_Epileptic_Encephalopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/KCNQ2_Developmental_and_Epileptic_Encephalopathy.html#dataset-geo-gse122584"}],"context_names":["KCNQ2 Developmental and Epileptic Encephalopathy"],"disease_names":["KCNQ2 Developmental and Epileptic Encephalopathy"],"disease_name":"KCNQ2 Developmental and Epileptic Encephalopathy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/KCNQ2_Developmental_and_Epileptic_Encephalopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/KCNQ2_Developmental_and_Epileptic_Encephalopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/KCNQ2_Developmental_and_Epileptic_Encephalopathy.html#dataset-geo-gse122584"]},{"id":"dataset:geo:gse123568","accession":"geo:GSE123568","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE123568","title":"Identification of Potential Biomarkers for Improving the Precision of Early Detection of Steroid-induced Osteonecrosis of the Femoral Head","alternate_titles":[],"description":"Early diagnosis and prompt treatment are the key to prevent collapse and delay Steroid-induced Osteonecrosis of the Femoral Head(SONFH) progression.The aim of this study was to identify potential biomarkers for the diagnosis of SONFH, so to improve the efficiency of early diagnosis. Microarray analysis based on the 30 SONFH patients and 10 non-SONFH patients(following steroid administration) was performed to screen SONFH-related genes.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[40],"sample_count":40,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37313692"],"publication_contexts":[{"context_id":"disorder:Osteonecrosis","publication":"PMID:37313692"}],"publication":"PMID:37313692","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37313692","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Osteonecrosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Osteonecrosis","name":"Osteonecrosis","kind":"Disorder","source_path":"kb/disorders/Osteonecrosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Osteonecrosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Osteonecrosis.html#dataset-geo-gse123568"}],"context_names":["Osteonecrosis"],"disease_names":["Osteonecrosis"],"disease_name":"Osteonecrosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Osteonecrosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Osteonecrosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Osteonecrosis.html#dataset-geo-gse123568"]},{"id":"dataset:geo:gse124208","accession":"geo:GSE124208","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE124208","title":"Rescue of premature aging defects in Cockayne Syndrome Derived Stem Cells by Targeted Gene Correction","alternate_titles":[],"description":"Cockayne Syndrome (CS) is a rare autosomal recessive inherited disorder characterized by a variety of clinical features including sensitivity to sunlight, progressive neurological abnormalities and appearance of premature aging. However, the pathogenesis of CS yet remains unclear due to the limitations of current disease models. Here we generate integration free-induced pluripotent stem cells (iPSCs) from CS patient fibroblast bearing mutations in CSB/ERCC6 and further derive isogenic gene corrected (GC)-iPSCs using CRISPR/Cas9 system.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[24],"sample_count":24,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:31037510"],"publication_contexts":[{"context_id":"disorder:Cockayne_Syndrome","publication":"PMID:31037510"}],"publication":"PMID:31037510","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/31037510","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Cockayne Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Cockayne_Syndrome","name":"Cockayne Syndrome","kind":"Disorder","source_path":"kb/disorders/Cockayne_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cockayne_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cockayne_Syndrome.html#dataset-geo-gse124208"}],"context_names":["Cockayne Syndrome"],"disease_names":["Cockayne Syndrome"],"disease_name":"Cockayne Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cockayne_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cockayne_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cockayne_Syndrome.html#dataset-geo-gse124208"]},{"id":"dataset:geo:gse124663","accession":"geo:GSE124663","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE124663","title":"Universal correction of blood coagulation factor VIII in patient-derived induced pluripotent stem cells using CRISPR/Cas9","alternate_titles":[],"description":"Confirmation of the nuclease acivities at the On- and Off-target sites; Hemophilia A (HA) is caused by genetic mutations in the blood coagulation factor VIII (FVIII). Genome editing approaches can be used to target the mutated site itself in patient-derived induced pluripotent stem cells (iPSCs). However, these approaches can be hampered by difficulty preparing thousands of editing platforms for each corresponding variant found in HA patients. Here, we report a universal approach to correct the various mutations in HA patient iPSCs by the targeted insertion of the FVIII gene into the human H11 site via CRISPR/Cas9.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[114],"sample_count":114,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:31105049"],"publication_contexts":[{"context_id":"disorder:Hemophilia_A","publication":"PMID:31105049"}],"publication":"PMID:31105049","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/31105049","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Hemophilia A (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Hemophilia_A","name":"Hemophilia A","kind":"Disorder","source_path":"kb/disorders/Hemophilia_A.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hemophilia_A.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hemophilia_A.html#dataset-geo-gse124663"}],"context_names":["Hemophilia A"],"disease_names":["Hemophilia A"],"disease_name":"Hemophilia A","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hemophilia_A.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hemophilia_A.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hemophilia_A.html#dataset-geo-gse124663"]},{"id":"dataset:geo:gse124756","accession":"geo:GSE124756","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE124756","title":"Comparison of Transcriptional Signatures of Three Staphylococcal Superantigenic Toxins in Human Epidermal Melanocytes","alternate_titles":[],"description":"The focus of this study was to determine the distinct and shared mechanisms of response to three toxins of the superantigenic family, namely SEA, SEB and TSST-1.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[19],"sample_count":19,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:35740423"],"publication_contexts":[{"context_id":"disorder:Toxic_Shock_Syndrome","publication":"PMID:35740423"}],"publication":"PMID:35740423","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35740423","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Toxic Shock Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-11. Relevance triaged manually: a human-cell comparison of the three staphylococcal superantigens named in this entry's toxin-production node."],"contexts":[{"id":"disorder:Toxic_Shock_Syndrome","name":"Toxic Shock Syndrome","kind":"Disorder","source_path":"kb/disorders/Toxic_Shock_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Toxic_Shock_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Toxic_Shock_Syndrome.html#dataset-geo-gse124756"}],"context_names":["Toxic Shock Syndrome"],"disease_names":["Toxic Shock Syndrome"],"disease_name":"Toxic Shock Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Toxic_Shock_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Toxic_Shock_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Toxic_Shock_Syndrome.html#dataset-geo-gse124756"]},{"id":"dataset:geo:gse125076","accession":"geo:GSE125076","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE125076","title":"A mouse model of acute post-surgical pain","alternate_titles":[],"description":"Pain is the leading cause of disability in the developed world but remains a poorly treated condition. Specifically, post-surgical pain continues to be a frequent and undermanaged condition. Here, we investigate the analgesic potential of pharmacological NaV1.7 inhibition in a mouse model of acute post-surgical pain, based on incision of the plantar skin and underlying muscle of the hind paw. We demonstrate that local and systemic treatment with the selective NaV1.7 inhibitor μ-theraphotoxin-Pn3a is effectively anti-allodynic in this model and completely reverses mechanical hypersensitivity in the absence of motor adverse effects.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:31335646"],"publication_contexts":[{"context_id":"disorder:Acute_Post-Surgical_Pain","publication":"PMID:31335646"}],"publication":"PMID:31335646","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/31335646","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Acute Post-Surgical Pain (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Acute_Post-Surgical_Pain","name":"Acute Post-Surgical Pain","kind":"Disorder","source_path":"kb/disorders/Acute_Post-Surgical_Pain.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Acute_Post-Surgical_Pain.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Acute_Post-Surgical_Pain.html#dataset-geo-gse125076"}],"context_names":["Acute Post-Surgical Pain"],"disease_names":["Acute Post-Surgical Pain"],"disease_name":"Acute Post-Surgical Pain","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Acute_Post-Surgical_Pain.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Acute_Post-Surgical_Pain.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Acute_Post-Surgical_Pain.html#dataset-geo-gse125076"]},{"id":"dataset:geo:gse125977","accession":"geo:GSE125977","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE125977","title":"MicroRNA and mRNA profiling in the idiopathic inflammatory myopathies","alternate_titles":[],"description":"Objectives: The idiopathic inflammatory myopathies (IIMs) are heterogeneous autoimmune conditions of skeletal muscle inflammation and weakness. MicroRNAs (miRNAs) are short, non-coding RNA which regulate gene expression of target mRNAs. The aim of this study was to profile miRNA and mRNA in IIM and identify miRNA-mRNA relationships which may be relevant to disease. Materials and methods: mRNA and miRNA in whole blood samples from 7 polymyositis (PM), 7 dermatomyositis (DM), 5 inclusion body myositis (IBM) and 5 non-myositis controls was profiled using next generation RNA sequencing. Gene ontology and pathway analyses were performed using GOseq and Ingenuity Pathway Analysis.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[48],"sample_count":48,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:32529172"],"publication_contexts":[{"context_id":"disorder:Polymyositis","publication":"PMID:32529172"}],"publication":"PMID:32529172","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32529172","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Polymyositis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Polymyositis","name":"Polymyositis","kind":"Disorder","source_path":"kb/disorders/Polymyositis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Polymyositis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Polymyositis.html#dataset-geo-gse125977"}],"context_names":["Polymyositis"],"disease_names":["Polymyositis"],"disease_name":"Polymyositis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Polymyositis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Polymyositis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Polymyositis.html#dataset-geo-gse125977"]},{"id":"dataset:geo:gse126322","accession":"geo:GSE126322","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE126322","title":"Remodeling of active endothelial enhancers is associated with aberrant gene-regulatory networks in pulmonary arterial hypertension [ChIP-seq]","alternate_titles":[],"description":"Chromatin profiling (H3K27ac, H3K4me1, H3K4me3 ChIP-seq) of pulmonary arterial endothelial cells extracted from the lungs of 10 patients with pulmonary arterial hypertension and 9 controls, showing large-scale remodeling of the active enhancer landscape while promoters and gene expression were unchanged.","alternate_descriptions":["H3K27ac, H3K4me1 and H3K4me3 ChIP-sequencing of pulmonary arterial endothelial cells explanted and cultured from PAH patients and controls, reporting large-scale remodeling of the active enhancer landscape with unchanged promoters and gene expression.","Pulmonary Arterial Hypertension (PAH) is a cardiovascular disease characterized by progressively increasing blood pressure as a result of obliteration and loss of pulmonary arteries. We have extracted pulmonary arterial endothelial cells from lungs of a cohort of PAH patients (n=10) and controls (n=9), cultured the cells for 3-5 passages, and performed chromatin (H3K27ac, H3K4me1, and H3K4me3 ChIP-Seq), expression (RNA-Seq) and chromatin interaction profiling (ChIA-PET). We observed a large-scale remodelling of the active chromatin landscape at enhancers while promoters and gene expression remained unchanged."],"data_types":["CHIP_SEQ"],"data_type_labels":["Chromatin immunoprecipitation sequencing"],"data_type_label":"Chromatin immunoprecipitation sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[55],"sample_count":55,"conditions":["pulmonary arterial hypertension","control"],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:1078","label":"BMPR2","display_label":"BMPR2","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/1078"}],"genes":["BMPR2"],"platforms":["ChIP-seq of H3K27ac, H3K4me1 and H3K4me3"],"platform":"ChIP-seq of H3K27ac, H3K4me1 and H3K4me3","publications":["PMID:32245974"],"publication_contexts":[{"context_id":"disorder:Eisenmenger_Syndrome","publication":"PMID:32245974"},{"context_id":"disorder:Idiopathic_Pulmonary_Arterial_Hypertension","publication":"PMID:32245974"},{"context_id":"disorder:Pulmonary_hypertension","publication":"PMID:32245974"}],"publication":"PMID:32245974","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32245974","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Relevance triage, stated plainly: this dataset contains NO Eisenmenger syndrome and no congenital heart disease samples. Its cohort is pulmonary arterial hypertension generally. It is included solely because this entry declares `conforms_to` against `pulmonary_vascular_remodeling#Pulmonary Endothelial Dysfunction and Impaired BMP Signaling`, and this is primary human pulmonary artery endothelial cell data for exactly that conformed node; it cannot support any Eisenmenger-specific claim, and no evidence item cites it. No Eisenmenger-specific transcriptomic, epigenomic, or proteomic dataset exists in GEO. All 12 candidates surfaced by dataset discovery were gene-only matches on BMPR2 with no congenital-heart-disease content, so this is the closest mechanistically relevant primary dataset rather than a disease match.","Relevance triage: DIRECT for the endothelial-dysfunction node, with the caveat that the cohort is PAH-wide rather than IPAH-restricted and the cells were passaged three to five times in culture before profiling. Accession resolved 2026-09-03.","Identified by GEO DataSets index search for Pulmonary hypertension (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Eisenmenger_Syndrome","name":"Eisenmenger Syndrome","kind":"Disorder","source_path":"kb/disorders/Eisenmenger_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Eisenmenger_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Eisenmenger_Syndrome.html#dataset-geo-gse126322"},{"id":"disorder:Idiopathic_Pulmonary_Arterial_Hypertension","name":"Idiopathic Pulmonary Arterial Hypertension","kind":"Disorder","source_path":"kb/disorders/Idiopathic_Pulmonary_Arterial_Hypertension.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Idiopathic_Pulmonary_Arterial_Hypertension.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Idiopathic_Pulmonary_Arterial_Hypertension.html#dataset-geo-gse126322"},{"id":"disorder:Pulmonary_hypertension","name":"Pulmonary_hypertension","kind":"Disorder","source_path":"kb/disorders/Pulmonary_hypertension.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pulmonary_hypertension.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pulmonary_hypertension.html#dataset-geo-gse126322"}],"context_names":["Eisenmenger Syndrome","Idiopathic Pulmonary Arterial Hypertension","Pulmonary_hypertension"],"disease_names":["Eisenmenger Syndrome","Idiopathic Pulmonary Arterial Hypertension","Pulmonary_hypertension"],"disease_name":"Eisenmenger Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Eisenmenger_Syndrome.yaml","kb/disorders/Idiopathic_Pulmonary_Arterial_Hypertension.yaml","kb/disorders/Pulmonary_hypertension.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Eisenmenger_Syndrome.yaml","https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Idiopathic_Pulmonary_Arterial_Hypertension.yaml","https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pulmonary_hypertension.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Eisenmenger_Syndrome.html#dataset-geo-gse126322","https://dismech.monarchinitiative.org/pages/disorders/Idiopathic_Pulmonary_Arterial_Hypertension.html#dataset-geo-gse126322","https://dismech.monarchinitiative.org/pages/disorders/Pulmonary_hypertension.html#dataset-geo-gse126322"]},{"id":"dataset:geo:gse126352","accession":"geo:GSE126352","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE126352","title":"Transcriptomes of human monocytes from patients with familial hypercholesterolemia before and after statin treatment","alternate_titles":[],"description":"RNA sequencing of circulating monocytes from familial hypercholesterolemia patients before and after three months of statin therapy, generated to ask whether lowering LDL reverses the trained-immunity phenotype of those cells. Relevant here to the monocyte arm of the arterial cascade and to what statin therapy does and does not undo. Relevance caveat: the cohort is defined clinically as familial hypercholesterolemia and the series does not report LDLR genotypes, so it is class-level rather than LDLR-specific.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:31204280"],"publication_contexts":[{"context_id":"disorder:LDLR-Related_Familial_Hypercholesterolemia","publication":"PMID:31204280"}],"publication":"PMID:31204280","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/31204280","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE126352","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE126352","reference_title":"Transcriptomes of human monocytes from patients with familial hypercholesterolemia before and after statin treatment","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"in this study we compared the transcriptomes of patients with hypercholesterolemia before and after statin treatment for 3 months","explanation":"The repository record's own statement of the design, which is what establishes the before/after statin comparison this record is cited for."}],"notes":["Surfaced by `just discover-datasets` as a DIRECT candidate and confirmed against the linked publication before inclusion."],"contexts":[{"id":"disorder:LDLR-Related_Familial_Hypercholesterolemia","name":"LDLR-Related Familial Hypercholesterolemia","kind":"Disorder","source_path":"kb/disorders/LDLR-Related_Familial_Hypercholesterolemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/LDLR-Related_Familial_Hypercholesterolemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/LDLR-Related_Familial_Hypercholesterolemia.html#dataset-geo-gse126352"}],"context_names":["LDLR-Related Familial Hypercholesterolemia"],"disease_names":["LDLR-Related Familial Hypercholesterolemia"],"disease_name":"LDLR-Related Familial Hypercholesterolemia","same_context_model_ids":["model:kb/disorders/LDLR-Related_Familial_Hypercholesterolemia.yaml:Activity-normalized prime editing saturation screen of LDLR coding variants","model:kb/disorders/LDLR-Related_Familial_Hypercholesterolemia.yaml:CHO-ldlA7 heterologous LDLR variant expression assay","model:kb/disorders/LDLR-Related_Familial_Hypercholesterolemia.yaml:J.D. fibroblast strain (internalization-defective LDLR alleles)","model:kb/disorders/LDLR-Related_Familial_Hypercholesterolemia.yaml:JD iPSC-derived hepatocyte-like cells"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/LDLR-Related_Familial_Hypercholesterolemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/LDLR-Related_Familial_Hypercholesterolemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/LDLR-Related_Familial_Hypercholesterolemia.html#dataset-geo-gse126352"]},{"id":"dataset:geo:gse126416","accession":"geo:GSE126416","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE126416","title":"RNA-deep sequencing (RNA-Seq) analysis of dy2J/dy2J (Lama2-CMD mouse model), mdx (DMD mouse model) and Wild-type skeletal muscles","alternate_titles":[],"description":"Whole-transcriptome profiling of dy2J/dy2J skeletal muscle at eight weeks against mdx and wild-type. The mdx comparison is what makes it useful here: it separates what is shared with a sarcolemmal dystrophy generally from what is specific to laminin-alpha2 deficiency, and the specific finding is a downregulated rather than upregulated regeneration programme.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"house mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[8],"sample_count":8,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:6482","label":"LAMA2","display_label":"LAMA2","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/6482"}],"genes":["LAMA2"],"platforms":[],"platform":null,"publications":["PMID:31348492"],"publication_contexts":[{"context_id":"disorder:Congenital_Merosin-deficient_Muscular_Dystrophy_1A","publication":"PMID:31348492"}],"publication":"PMID:31348492","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/31348492","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE126416","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE126416","reference_title":"RNA-deep sequencing (RNA-Seq) analysis of dy2J/dy2J (Lama2-CMD mouse model), mdx (DMD mouse model) and Wild-type skeletal muscles","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"Interestingly, significant downregulation of Pax7 was detected in dy2J/dy2J compared to upregulation of this key regeneration gene in mdx mice.","explanation":"Supports the Abortive Muscle Regeneration node with a transcriptomic contrast showing the regenerative programme is suppressed in laminin-alpha2 deficiency where it is driven in a dystrophin-deficient control."},{"reference":"GEO:GSE126416","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE126416","reference_title":"RNA-deep sequencing (RNA-Seq) analysis of dy2J/dy2J (Lama2-CMD mouse model), mdx (DMD mouse model) and Wild-type skeletal muscles","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"Enrichment pathway analysis using Ingenuity Pathway Analysis (IPA) showed enrichment of inflammation, fibrosis, cellular movement, migration and proliferation of cells, apoptosis and necrosis in both mouse models","explanation":"Independently recovers the inflammation, fibrosis and apoptosis arms of the curated pathophysiology chain from an unbiased transcriptomic analysis."}],"notes":[],"contexts":[{"id":"disorder:Congenital_Merosin-deficient_Muscular_Dystrophy_1A","name":"Congenital Merosin-deficient Muscular Dystrophy 1A","kind":"Disorder","source_path":"kb/disorders/Congenital_Merosin-deficient_Muscular_Dystrophy_1A.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Congenital_Merosin-deficient_Muscular_Dystrophy_1A.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Congenital_Merosin-deficient_Muscular_Dystrophy_1A.html#dataset-geo-gse126416"}],"context_names":["Congenital Merosin-deficient Muscular Dystrophy 1A"],"disease_names":["Congenital Merosin-deficient Muscular Dystrophy 1A"],"disease_name":"Congenital Merosin-deficient Muscular Dystrophy 1A","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Congenital_Merosin-deficient_Muscular_Dystrophy_1A.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Congenital_Merosin-deficient_Muscular_Dystrophy_1A.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Congenital_Merosin-deficient_Muscular_Dystrophy_1A.html#dataset-geo-gse126416"]},{"id":"dataset:geo:gse127314","accession":"geo:GSE127314","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE127314","title":"Effects of 1,25-dihydroxyvitamin D (1,25D) on global gene expression of human fibroblasts with (CO) or without (MUT) a functional VDR","alternate_titles":[],"description":"Microarray profiling of primary skin fibroblasts from one homozygous VDR p.Arg30* VDDR2A patient and an age- and sex-matched control after vehicle or 10 nM calcitriol for 24 hours. Fifteen quality-controlled arrays represent four control-vehicle, four control-calcitriol, three mutant-vehicle, and four mutant-calcitriol samples.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"CL:0000057","label":"fibroblast","display_label":"fibroblast","url":"http://purl.obolibrary.org/obo/CL_0000057"}],"sample_type_labels":["fibroblast"],"sample_counts":[15],"sample_count":15,"conditions":["homozygous VDR p.Arg30* patient fibroblasts","matched control fibroblasts","vehicle or 10 nM calcitriol for 24 hours"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["Affymetrix GeneChip Human Gene 2.0 ST Array"],"platform":"Affymetrix GeneChip Human Gene 2.0 ST Array","publications":["PMID:30959822"],"publication_contexts":[{"context_id":"disorder:Vitamin_D-Dependent_Rickets_Type_2A","publication":"PMID:30959822"}],"publication":"PMID:30959822","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/30959822","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:30959822","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30959822","reference_title":"Transcriptomic Response to 1,25-Dihydroxyvitamin D in Human Fibroblasts with or without a Functional Vitamin D Receptor (VDR): Novel Target Genes and Insights into VDR Basal Transcriptional Activity.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The array data were submitted to the National Center for Biotechnology Information Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo) under series accession no. GSE127314.","explanation":"Directly identifies the public dataset accession in the source publication."}],"notes":["GEO metadata and accession were independently resolved with just verify-datasets on 2026-08-20."],"contexts":[{"id":"disorder:Vitamin_D-Dependent_Rickets_Type_2A","name":"Vitamin D-Dependent Rickets Type 2A","kind":"Disorder","source_path":"kb/disorders/Vitamin_D-Dependent_Rickets_Type_2A.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Vitamin_D-Dependent_Rickets_Type_2A.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Vitamin_D-Dependent_Rickets_Type_2A.html#dataset-geo-gse127314"}],"context_names":["Vitamin D-Dependent Rickets Type 2A"],"disease_names":["Vitamin D-Dependent Rickets Type 2A"],"disease_name":"Vitamin D-Dependent Rickets Type 2A","same_context_model_ids":["model:kb/disorders/Vitamin_D-Dependent_Rickets_Type_2A.yaml:Patient-Derived p.Arg30* VDR Dermal Fibroblasts"],"candidate_model_ids":["model:kb/disorders/Vitamin_D-Dependent_Rickets_Type_2A.yaml:Patient-Derived p.Arg30* VDR Dermal Fibroblasts"],"association_basis":"Same publication as a NAM (candidate)","nam_disease_context":"Same publication as a NAM (candidate)","source_paths":["kb/disorders/Vitamin_D-Dependent_Rickets_Type_2A.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Vitamin_D-Dependent_Rickets_Type_2A.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Vitamin_D-Dependent_Rickets_Type_2A.html#dataset-geo-gse127314"]},{"id":"dataset:geo:gse127478","accession":"geo:GSE127478","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE127478","title":"Mitochondrial 3243A > G mutation confers pro-atherogenic and pro-inflammatory properties in MELAS iPS derived endothelial cells","alternate_titles":[],"description":"RNA-seq of endothelial cells differentiated from MELAS patient iPSCs and an isogenic control, characterising reactive oxygen species, oxidised LDL, VCAM-1 expression, and monocyte adhesion.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:31641105"],"publication_contexts":[{"context_id":"disorder:MELAS_Syndrome","publication":"PMID:31641105"}],"publication":"PMID:31641105","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/31641105","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:31641105","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/31641105","reference_title":"Mitochondrial 3243A > G mutation confers pro-atherogenic and pro-inflammatory properties in MELAS iPS derived endothelial cells.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"in addition to endothelial dysfunction, diseased endothelial cells (ECs) were found to be pro-atherogenic and pro-inflammation due to high levels of ROS and Ox-LDLs, and high basal expressions of VCAM-1","explanation":"Provides a cell-autonomous mechanism for the vascular arm of the controversy in isogenic human endothelium."}],"notes":["The vascular arm of the stroke-like-episode controversy in an isogenic human system. Note what it does and does not show: it establishes that m.3243A>G endothelium is intrinsically dysfunctional and inflammatory, which the vascular hypothesis requires, but endothelial dysfunction in a dish is not an ischemic stroke-like episode in cortex."],"contexts":[{"id":"disorder:MELAS_Syndrome","name":"MELAS Syndrome","kind":"Disorder","source_path":"kb/disorders/MELAS_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MELAS_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/MELAS_Syndrome.html#dataset-geo-gse127478"}],"context_names":["MELAS Syndrome"],"disease_names":["MELAS Syndrome"],"disease_name":"MELAS Syndrome","same_context_model_ids":["model:kb/disorders/MELAS_Syndrome.yaml:m.3243A>G patient iPSC-derived neurons"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/MELAS_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MELAS_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/MELAS_Syndrome.html#dataset-geo-gse127478"]},{"id":"dataset:geo:gse129091","accession":"geo:GSE129091","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE129091","title":"Quantitative variation in m.3243A>G mutation produce discrete changes in energy metabolism","alternate_titles":[],"description":"Expression profiling of cells carrying low versus high m.3243A>G mutation load against wild type, paired with bioenergetic, biogenesis, and fuel-catabolism assays, framed explicitly around the MELAS-versus-MIDD divergence.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:30962477"],"publication_contexts":[{"context_id":"disorder:MELAS_Syndrome","publication":"PMID:30962477"}],"publication":"PMID:30962477","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/30962477","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:30962477","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/30962477","reference_title":"Quantitative Variation in m.3243A > G Mutation Produce Discrete Changes in Energy Metabolism.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"despite striking similarities in the energy metabolic gene expression signature, the mitochondrial bioenergetics, biogenesis and fuel catabolic functions are distinct in cells harboring low or high levels of the m.3243 A > G mutation compared to wild type cells","explanation":"Shows the low-load and high-load states differ functionally while looking alike transcriptionally, a caution for biomarker work that relies on expression signatures."}],"notes":["Directly targets the question the entry records as open - why the same variant yields MELAS at high load and MIDD at low load - and reports that the transcriptional signatures are similar while the functional states diverge, which argues against expression profiling alone resolving the gap."],"contexts":[{"id":"disorder:MELAS_Syndrome","name":"MELAS Syndrome","kind":"Disorder","source_path":"kb/disorders/MELAS_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MELAS_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/MELAS_Syndrome.html#dataset-geo-gse129091"}],"context_names":["MELAS Syndrome"],"disease_names":["MELAS Syndrome"],"disease_name":"MELAS Syndrome","same_context_model_ids":["model:kb/disorders/MELAS_Syndrome.yaml:m.3243A>G patient iPSC-derived neurons"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/MELAS_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MELAS_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/MELAS_Syndrome.html#dataset-geo-gse129091"]},{"id":"dataset:geo:gse129308","accession":"geo:GSE129308","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE129308","title":"Molecular signatures underlying neurofibrillary tangle susceptibility in Alzheimer's disease","alternate_titles":[],"description":"Transcriptomes of single somas bearing neurofibrillary tangles compared with tangle-free somas isolated from the same human Alzheimer brains. The within-donor design controls for donor-level confounding when asking what distinguishes an aggregation-prone from an aggregation-resistant neuron.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"Homo sapiens","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0000956","label":"cerebral cortex","display_label":"cerebral cortex","url":"http://purl.obolibrary.org/obo/UBERON_0000956"}],"sample_type_labels":["cerebral cortex"],"sample_counts":[27],"sample_count":27,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:35882228"],"publication_contexts":[{"context_id":"disorder:Alzheimer_Disease","publication":"PMID:35882228"}],"publication":"PMID:35882228","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35882228","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["The sharpest available human contrast for three separate questions curated in this entry: which neurons are selectively vulnerable, whether senescent cells are the tangle-bearing excitatory neurons reported in PMID:35531351, and whether necroptosis effectors are enriched in pathology-bearing neurons. Accession resolved against the GEO API with `just verify-datasets`. Note that the GEO record's own linked citation is PMID:41620473, a later reuse of the series (Dharshini et al. 2026 on layer 4 resilience); the originating study is Otero-Garcia et al. 2022 (PMID:35882228), whose title matches the series title. Do not take the GEO-linked PMID as the source publication here."],"contexts":[{"id":"disorder:Alzheimer_Disease","name":"Alzheimer Disease","kind":"Disorder","source_path":"kb/disorders/Alzheimer_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alzheimer_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Alzheimer_Disease.html#dataset-geo-gse129308"}],"context_names":["Alzheimer Disease"],"disease_names":["Alzheimer Disease"],"disease_name":"Alzheimer Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Alzheimer_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alzheimer_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Alzheimer_Disease.html#dataset-geo-gse129308"]},{"id":"dataset:geo:gse129502","accession":"geo:GSE129502","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE129502","title":"TRMT10A associated RNA targets","alternate_titles":[],"description":"Human high-throughput sequencing profiling of the RNA species bound by TRMT10A, undertaken to define the enzyme's substrate repertoire in human cells rather than yeast. 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It is a gene-function dataset, not a patient cohort - it does not contain MSSGM1 case material. No evidence block: no exact-quote-bearing publication is attached to the accession."],"contexts":[{"id":"disorder:Microcephaly_Short_Stature_and_Impaired_Glucose_Metabolism_1","name":"Microcephaly, Short Stature, and Impaired Glucose Metabolism 1","kind":"Disorder","source_path":"kb/disorders/Microcephaly_Short_Stature_and_Impaired_Glucose_Metabolism_1.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Microcephaly_Short_Stature_and_Impaired_Glucose_Metabolism_1.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Microcephaly,_Short_Stature,_and_Impaired_Glucose_Metabolism_1.html#dataset-geo-gse129502"}],"context_names":["Microcephaly, Short Stature, and Impaired Glucose Metabolism 1"],"disease_names":["Microcephaly, Short Stature, and Impaired Glucose Metabolism 1"],"disease_name":"Microcephaly, Short Stature, and Impaired Glucose Metabolism 1","same_context_model_ids":["model:kb/disorders/Microcephaly_Short_Stature_and_Impaired_Glucose_Metabolism_1.yaml:Patient-derived iPSC beta-like cells (TRMT10A-deficient)","model:kb/disorders/Microcephaly_Short_Stature_and_Impaired_Glucose_Metabolism_1.yaml:TRMT10A silencing in rat INS-1E and human EndoC-betaH1 beta cells"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Microcephaly_Short_Stature_and_Impaired_Glucose_Metabolism_1.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Microcephaly_Short_Stature_and_Impaired_Glucose_Metabolism_1.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Microcephaly,_Short_Stature,_and_Impaired_Glucose_Metabolism_1.html#dataset-geo-gse129502"]},{"id":"dataset:geo:gse130125","accession":"geo:GSE130125","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE130125","title":"Delineating the molecular pathways regulated by IFN-gamma and IL-17 in the small intestines of humanized mice during staphylococcal superantigen-induced toxic shock syndrome","alternate_titles":[],"description":"RNASeq identified several pathways that were differentially expressed/regulated in the small intestines that correlated with intestinal failure during toxic shock syndrome caused by staphylococcal superantigen in a humanized mouse model","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[21],"sample_count":21,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:32676080"],"publication_contexts":[{"context_id":"disorder:Toxic_Shock_Syndrome","publication":"PMID:32676080"}],"publication":"PMID:32676080","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32676080","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Toxic Shock Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-11. Title, sample count, and organism are GEO's own values. Relevance triaged manually: the study is explicitly a staphylococcal superantigen-induced TSS model in HLA-humanized mice."],"contexts":[{"id":"disorder:Toxic_Shock_Syndrome","name":"Toxic Shock Syndrome","kind":"Disorder","source_path":"kb/disorders/Toxic_Shock_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Toxic_Shock_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Toxic_Shock_Syndrome.html#dataset-geo-gse130125"}],"context_names":["Toxic Shock Syndrome"],"disease_names":["Toxic Shock Syndrome"],"disease_name":"Toxic Shock Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Toxic_Shock_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Toxic_Shock_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Toxic_Shock_Syndrome.html#dataset-geo-gse130125"]},{"id":"dataset:geo:gse130749","accession":"geo:GSE130749","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE130749","title":"CBX2 is required to stabilize the testis pathway by repressing Wnt signaling","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["CHIP_SEQ"],"data_type_labels":["Chromatin immunoprecipitation sequencing"],"data_type_label":"Chromatin immunoprecipitation sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"house mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:31116734"],"publication_contexts":[{"context_id":"disorder:46_XY_Sex_Reversal_5","publication":"PMID:31116734"}],"publication":"PMID:31116734","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/31116734","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Quantitative H3K4me3 and H3K27me3 profiles of FACS-purified XX and XY gonadal supporting cells before (E10.5) and after (E13.5) sex determination, generated for the study that proposed the ovarian-derepression model. This is the one dataset found that is actually about CBX2 in gonadal sex determination: a dataset search on the gene name otherwise returns CBX2 chromatin and cancer studies, and one on the disease name returns word matches on \"sex reversal\" in unrelated cohorts. Those were triaged out rather than listed. The data are murine gonadal supporting cells, not patient material; no human CBX2-patient dataset exists."],"contexts":[{"id":"disorder:46_XY_Sex_Reversal_5","name":"46,XY Sex Reversal 5","kind":"Disorder","source_path":"kb/disorders/46_XY_Sex_Reversal_5.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/46_XY_Sex_Reversal_5.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/46,XY_Sex_Reversal_5.html#dataset-geo-gse130749"}],"context_names":["46,XY Sex Reversal 5"],"disease_names":["46,XY Sex Reversal 5"],"disease_name":"46,XY Sex Reversal 5","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association 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recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE131069","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE131069","reference_title":"Differential gene expression in human RAF1 S257L/+ and isogenic corrected iPSC-derived cardiomyocytes","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Hence, to gain insights into the transcriptional alterations induced by the NS-associated RAF1S257L/+ mutation in human iPSC-derived cardiomyocytes, we performed quantitative transcriptome profiling by RNA-sequencing.","explanation":"Supports a mutation-specific human cardiomyocyte transcriptomic resource linking RAF1-driven signaling dysregulation to Noonan cardiac phenotypes."}],"notes":[],"contexts":[{"id":"disorder:Noonan_Syndrome","name":"Noonan 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NAM","source_paths":["kb/disorders/Noonan_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Noonan_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Noonan_Syndrome.html#dataset-geo-gse131069"]},{"id":"dataset:geo:gse13162","accession":"geo:GSE13162","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE13162","title":"Expression data from postmortem human brain samples with and without FTLD-U","alternate_titles":[],"description":"Microarray expression profiling of frontal cortex, hippocampus, and cerebellum from FTLD-U and control brains.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo 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After quality filtering, 98,504 cells retained including 16,046 epithelial, 5,468 stromal, and 76,990 immune cells.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0002048","label":"lung","display_label":"lung","url":"http://purl.obolibrary.org/obo/UBERON_0002048"}],"sample_type_labels":["lung"],"sample_counts":[26],"sample_count":26,"conditions":["NSCLC tumor tissue","adjacent normal lung tissue"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Comprehensive single-cell atlas identifying eight major cell types. Resolves tumor-infiltrating immune cell heterogeneity relevant to immunotherapy response. Part of integrated NSCLC scRNA-seq resource."],"contexts":[{"id":"disorder:Non-Small_Cell_Lung_Cancer","name":"Non-Small Cell Lung Cancer","kind":"Disorder","source_path":"kb/disorders/Non-Small_Cell_Lung_Cancer.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Non-Small_Cell_Lung_Cancer.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Non-Small_Cell_Lung_Cancer.html#dataset-geo-gse131907"}],"context_names":["Non-Small Cell Lung Cancer"],"disease_names":["Non-Small Cell Lung Cancer"],"disease_name":"Non-Small Cell Lung Cancer","same_context_model_ids":["model:kb/disorders/Non-Small_Cell_Lung_Cancer.yaml:Human orthotopic NSCLC lung organ-on-chip (Wyss Institute)"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Non-Small_Cell_Lung_Cancer.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Non-Small_Cell_Lung_Cancer.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Non-Small_Cell_Lung_Cancer.html#dataset-geo-gse131907"]},{"id":"dataset:geo:gse131954","accession":"geo:GSE131954","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE131954","title":"Spaceflight causes changes in gene expression, photoreceptor integrity, and oxidative stress-related damage in the murine retina","alternate_titles":[],"description":"Transcriptomic profiling of retinas from C57BL/6 mice flown aboard the ISS for 35 days, identifying 600 differentially expressed genes enriched for visual perception and phototransduction pathways.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:31527661"],"publication_contexts":[{"context_id":"disorder:Spaceflight_Associated_Neuro-Ocular_Syndrome","publication":"PMID:31527661"}],"publication":"PMID:31527661","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/31527661","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":[],"contexts":[{"id":"disorder:Spaceflight_Associated_Neuro-Ocular_Syndrome","name":"Spaceflight Associated Neuro-Ocular Syndrome","kind":"Disorder","source_path":"kb/disorders/Spaceflight_Associated_Neuro-Ocular_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Spaceflight_Associated_Neuro-Ocular_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Spaceflight_Associated_Neuro-Ocular_Syndrome.html#dataset-geo-gse131954"}],"context_names":["Spaceflight Associated Neuro-Ocular Syndrome"],"disease_names":["Spaceflight Associated Neuro-Ocular Syndrome"],"disease_name":"Spaceflight Associated Neuro-Ocular Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Spaceflight_Associated_Neuro-Ocular_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Spaceflight_Associated_Neuro-Ocular_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Spaceflight_Associated_Neuro-Ocular_Syndrome.html#dataset-geo-gse131954"]},{"id":"dataset:geo:gse132058","accession":"geo:GSE132058","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE132058","title":"Hepatic arginase deficiency fosters dysmyelination during postnatal CNS development","alternate_titles":[],"description":"Deficiency of arginase is associated with hyperargininemia, and unlike the other disorders of the urea cycle, the major mechanism of metabolism of nitrogen in terrestrial mammals, are characteristic and prominent features that include spastic diplegia/tetraplegia, clonus, and hyperreflexia; loss of ambulation, intellectual disability and progressive neurological decline are other signs. To gain greater insight into the unique neuromotor features, we performed gene expression profiling of the motor cortex of a well-characterized murine model of the disorder. Co-expression network analysis suggested an abnormality with myelination, which was supported by limited existing human data.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[24],"sample_count":24,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:31484827"],"publication_contexts":[{"context_id":"disorder:Arginase_Deficiency","publication":"PMID:31484827"}],"publication":"PMID:31484827","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/31484827","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Arginase Deficiency (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Arginase_Deficiency","name":"Arginase Deficiency","kind":"Disorder","source_path":"kb/disorders/Arginase_Deficiency.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Arginase_Deficiency.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Arginase_Deficiency.html#dataset-geo-gse132058"}],"context_names":["Arginase Deficiency"],"disease_names":["Arginase Deficiency"],"disease_name":"Arginase Deficiency","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Arginase_Deficiency.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Arginase_Deficiency.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Arginase_Deficiency.html#dataset-geo-gse132058"]},{"id":"dataset:geo:gse132840","accession":"geo:GSE132840","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE132840","title":"eXcision Repair-sequencing (XR-seq) to map UV induced damage in U2OS cells and in U2OS cells in which CSA or UVSSA genes were knocked out","alternate_titles":[],"description":"Genome-wide maps of UV-damage excision repair in wild-type human cells and in CSA- and UVSSA-knockout cells, with complementation by wild-type and mutant UVSSA. Measures the repair step this entry's mechanism nodes describe, in the same isogenic knockout system curated under experimental_models.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[9],"sample_count":9,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:29304","label":"UVSSA","display_label":"UVSSA","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/29304"},{"id":"hgnc:3439","label":"ERCC8","display_label":"ERCC8","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/3439"}],"genes":["UVSSA","ERCC8"],"platforms":[],"platform":null,"publications":["PMID:32355176"],"publication_contexts":[{"context_id":"disorder:UV-Sensitive_Syndrome","publication":"PMID:32355176"}],"publication":"PMID:32355176","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32355176","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE132840","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE132840","reference_title":"eXcision Repair-sequencing (XR-seq) to map UV induced damage in U2OS cells and in U2OS cells in which CSA or UVSSA genes were knocked out","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Complementation of UVSSA knockout with WT or mutant proteins shows UVSSA is a core component of human transcription coupled repair.","explanation":"The repository's own summary states what the experiment established, which is the UVSSA role this entry's mechanism nodes assert."}],"notes":["The most directly on-topic of the four candidates returned by just discover-datasets: it perturbs two of the three causal genes and measures the repair step itself, and its linked publication (PMID:32355176) is already cited here."],"contexts":[{"id":"disorder:UV-Sensitive_Syndrome","name":"UV-Sensitive Syndrome","kind":"Disorder","source_path":"kb/disorders/UV-Sensitive_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/UV-Sensitive_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/UV-Sensitive_Syndrome.html#dataset-geo-gse132840"}],"context_names":["UV-Sensitive Syndrome"],"disease_names":["UV-Sensitive Syndrome"],"disease_name":"UV-Sensitive Syndrome","same_context_model_ids":["model:kb/disorders/UV-Sensitive_Syndrome.yaml:Isogenic TC-NER knockout human cell lines","model:kb/disorders/UV-Sensitive_Syndrome.yaml:Patient dermal fibroblast lines"],"candidate_model_ids":["model:kb/disorders/UV-Sensitive_Syndrome.yaml:Isogenic TC-NER knockout human cell lines"],"association_basis":"Same publication as a NAM (candidate)","nam_disease_context":"Same publication as a NAM (candidate)","source_paths":["kb/disorders/UV-Sensitive_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/UV-Sensitive_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/UV-Sensitive_Syndrome.html#dataset-geo-gse132840"]},{"id":"dataset:geo:gse133063","accession":"geo:GSE133063","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE133063","title":"A Novel Silent Mutation in the L1CAM Gene causing Fetal Hydrocephalus","alternate_titles":[],"description":"Human fetal case with an L1CAM variant causing hydrocephalus. Triaged as directly relevant: the disease and the causal gene both match the HSAS subtype curated in this entry, rather than merely sharing a gene symbol.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[1],"sample_count":1,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:31572438"],"publication_contexts":[{"context_id":"disorder:Congenital_Hydrocephalus","publication":"PMID:31572438"}],"publication":"PMID:31572438","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/31572438","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Discovered with just discover-datasets (DIRECT, gene:L1CAM match) and resolved with just verify-datasets. Relevance triaged manually per CLAUDE.md: verification proves existence, not aboutness. No evidence block — bulk-discovered dataset records carry provenance notes rather than manufactured quotes."],"contexts":[{"id":"disorder:Congenital_Hydrocephalus","name":"Congenital Hydrocephalus","kind":"Disorder","source_path":"kb/disorders/Congenital_Hydrocephalus.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Congenital_Hydrocephalus.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Congenital_Hydrocephalus.html#dataset-geo-gse133063"}],"context_names":["Congenital Hydrocephalus"],"disease_names":["Congenital Hydrocephalus"],"disease_name":"Congenital Hydrocephalus","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Congenital_Hydrocephalus.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Congenital_Hydrocephalus.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Congenital_Hydrocephalus.html#dataset-geo-gse133063"]},{"id":"dataset:geo:gse133801","accession":"geo:GSE133801","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE133801","title":"DNA methylation analysis of pineoblastoma","alternate_titles":[],"description":"Pineoblastoma is a rare and aggressive embryonal tumor of childhood. The molecular heterogeneity within has not been systematically evaluated. In this study, we used methylation profiling to compare the signatures of pineoblastoma and other pineal parenchymal tumors to a reference cohort of brain tumor entities (GSE90496) , clinically relevant epigenomic subgroups with characteristics genomic/transcriptomic features are described.","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[43],"sample_count":43,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:31802236"],"publication_contexts":[{"context_id":"disorder:Pineoblastoma","publication":"PMID:31802236"}],"publication":"PMID:31802236","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/31802236","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Pineoblastoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Pineoblastoma","name":"Pineoblastoma","kind":"Disorder","source_path":"kb/disorders/Pineoblastoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pineoblastoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pineoblastoma.html#dataset-geo-gse133801"}],"context_names":["Pineoblastoma"],"disease_names":["Pineoblastoma"],"disease_name":"Pineoblastoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Pineoblastoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pineoblastoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Pineoblastoma.html#dataset-geo-gse133801"]},{"id":"dataset:geo:gse134426","accession":"geo:GSE134426","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE134426","title":"Next Generation Sequencing Facilitated Cerebellum DNA Methylation Analysis of Essential Tremor Patients","alternate_titles":[],"description":"We report the RRBS-based cerebellum DNA methylation profiling of essential tremor (ET) patients and controls. By obtaining over thirty billion bases of sequence from bisulfited-converted DNA, we generated genome-wide methylation profile of human cerebellum tissue. We identified differential DNA methylation patterns in 735 genes at various gene parts, across 12 ET patients. Many of those differentially methylated CpGs in ET patients are located in upstream regulatory regions of genes. We further found that many differentially methylated genes in ET pateints are associated with neurodegenerative disease.","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[23],"sample_count":23,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:31886034"],"publication_contexts":[{"context_id":"disorder:Essential_Tremor","publication":"PMID:31886034"}],"publication":"PMID:31886034","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/31886034","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Essential Tremor (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Essential_Tremor","name":"Essential Tremor","kind":"Disorder","source_path":"kb/disorders/Essential_Tremor.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Essential_Tremor.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Essential_Tremor.html#dataset-geo-gse134426"}],"context_names":["Essential Tremor"],"disease_names":["Essential Tremor"],"disease_name":"Essential Tremor","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Essential_Tremor.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Essential_Tremor.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Essential_Tremor.html#dataset-geo-gse134426"]},{"id":"dataset:geo:gse134878","accession":"geo:GSE134878","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE134878","title":"Gene Expression Analysis of Essential Tremor via RNA-sequencing","alternate_titles":[],"description":"RNA-seq evaluation of post-mortem human cerebelllum from 33 patients with diagnosed Essential tremor, compared to 22 age-matched control patients. Two samples were under-sequenced and therefore removed from the final analysis. The raw data has been included in this submission.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[54],"sample_count":54,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:31707044"],"publication_contexts":[{"context_id":"disorder:Essential_Tremor","publication":"PMID:31707044"}],"publication":"PMID:31707044","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/31707044","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Essential Tremor (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Essential_Tremor","name":"Essential Tremor","kind":"Disorder","source_path":"kb/disorders/Essential_Tremor.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Essential_Tremor.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Essential_Tremor.html#dataset-geo-gse134878"}],"context_names":["Essential Tremor"],"disease_names":["Essential Tremor"],"disease_name":"Essential Tremor","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Essential_Tremor.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Essential_Tremor.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Essential_Tremor.html#dataset-geo-gse134878"]},{"id":"dataset:geo:gse135851","accession":"geo:GSE135851","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE135851","title":"Identification of the lymphangioleiomyomatosis cell and its uterine origin","alternate_titles":[],"description":"Lymphangioleiomyomatosis (LAM) is a metastasizing neoplasm of reproductive age women which causes cystic lung remodeling and progressive respiratory failure. While LAM lesions are known to contain abnormal smooth muscle-like cells which harbor mTOR activating mutations in TSC1 or TSC2, the tissue origins of the mutant “LAM cells” that invade the lung remain unclear. By employing single cell and single nuclear RNA sequencing on explanted LAM lungs, we identified a unique population of cells and associated signature genes and gene networks which were readily distinguished from those of endogenous lung cells.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[8],"sample_count":8,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:32603599"],"publication_contexts":[{"context_id":"disorder:Lymphangioleiomyomatosis","publication":"PMID:32603599"}],"publication":"PMID:32603599","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32603599","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Lymphangioleiomyomatosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Lymphangioleiomyomatosis","name":"Lymphangioleiomyomatosis","kind":"Disorder","source_path":"kb/disorders/Lymphangioleiomyomatosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Lymphangioleiomyomatosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Lymphangioleiomyomatosis.html#dataset-geo-gse135851"}],"context_names":["Lymphangioleiomyomatosis"],"disease_names":["Lymphangioleiomyomatosis"],"disease_name":"Lymphangioleiomyomatosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Lymphangioleiomyomatosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Lymphangioleiomyomatosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Lymphangioleiomyomatosis.html#dataset-geo-gse135851"]},{"id":"dataset:geo:gse136309","accession":"geo:GSE136309","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE136309","title":"Transcriptome analysis suggests a compensatory role of the cofactors coenzyme A and NAD+ in medium-chain acyl-CoA dehydrogenase knockout mice","alternate_titles":[],"description":"During fasting, mitochondrial fatty-acid β-oxidation (mFAO) is essential for the generation of glucose by the liver. Children with a loss-of-function deficiency in the mFAO enzyme medium-chain acyl-Coenzyme A dehydrogenase (MCAD) are at serious risk of life-threatening low blood glucose levels during fasting in combination with intercurrent disease. However, a subset of these children remains asymptomatic throughout life. In MCAD-deficient (MCAD-KO) mice, glucose levels are similar to those of wild-type (WT) mice, even during fasting. We investigated if metabolic adaptations in the liver may underlie the robustness of this KO mouse.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[32],"sample_count":32,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:31601874"],"publication_contexts":[{"context_id":"disorder:MCAD_Deficiency","publication":"PMID:31601874"}],"publication":"PMID:31601874","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/31601874","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Medium Chain Acyl-CoA Dehydrogenase Deficiency (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:MCAD_Deficiency","name":"Medium Chain Acyl-CoA Dehydrogenase Deficiency","kind":"Disorder","source_path":"kb/disorders/MCAD_Deficiency.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MCAD_Deficiency.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Medium_Chain_Acyl-CoA_Dehydrogenase_Deficiency.html#dataset-geo-gse136309"}],"context_names":["Medium Chain Acyl-CoA Dehydrogenase Deficiency"],"disease_names":["Medium Chain Acyl-CoA Dehydrogenase Deficiency"],"disease_name":"Medium Chain Acyl-CoA Dehydrogenase Deficiency","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/MCAD_Deficiency.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MCAD_Deficiency.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Medium_Chain_Acyl-CoA_Dehydrogenase_Deficiency.html#dataset-geo-gse136309"]},{"id":"dataset:geo:gse137081","accession":"geo:GSE137081","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE137081","title":"Effects of Spaceflight on Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Structure and Function","alternate_titles":[],"description":"RNA sequencing from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) cultured aboard the ISS for 5.5 weeks. Identified 2,635 differentially expressed genes including mitochondrial metabolism genes, with altered calcium handling in microgravity cultures. Provides insight into how microgravity affects human cardiac gene expression relevant to cardiomyopathy mechanisms.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0000948","label":"heart","display_label":"heart","url":"http://purl.obolibrary.org/obo/UBERON_0000948"}],"sample_type_labels":["heart"],"sample_counts":[],"sample_count":null,"conditions":["spaceflight microgravity","ground control","post-flight"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:31708475"],"publication_contexts":[{"context_id":"disorder:Hypertrophic_Cardiomyopathy","publication":"PMID:31708475"}],"publication":"PMID:31708475","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/31708475","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:31708475","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/31708475","reference_title":"Effects of Spaceflight on Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Structure and Function.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Exposure to microgravity on the ISS caused alterations in hiPSC-CM calcium handling. RNA-sequencing analysis demonstrated that 2,635 genes were differentially expressed among flight, post-flight, and ground control samples, including genes involved in mitochondrial metabolism.","explanation":"First study of human iPSC-derived cardiomyocytes on ISS. Calcium handling alterations and mitochondrial gene expression changes parallel mechanisms implicated in HCM pathophysiology."}],"notes":[],"contexts":[{"id":"disorder:Hypertrophic_Cardiomyopathy","name":"Hypertrophic Cardiomyopathy","kind":"Disorder","source_path":"kb/disorders/Hypertrophic_Cardiomyopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hypertrophic_Cardiomyopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy.html#dataset-geo-gse137081"}],"context_names":["Hypertrophic Cardiomyopathy"],"disease_names":["Hypertrophic Cardiomyopathy"],"disease_name":"Hypertrophic Cardiomyopathy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hypertrophic_Cardiomyopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hypertrophic_Cardiomyopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy.html#dataset-geo-gse137081"]},{"id":"dataset:geo:gse137129","accession":"geo:GSE137129","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE137129","title":"RNA-seq of UGP2 mutant human embryonic stem cells and in vitro differentiated neural stem cells","alternate_titles":[],"description":"Transcriptomic profiles from engineered UGP2 knockout, recurrent-variant knock-in, wild-type, and rescue human stem-cell models used to identify neural-lineage transcriptional consequences of UGP2 deficiency.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":["UGP2 knockout","recurrent variant knock-in","wild-type control","long-isoform rescue"],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:12527","label":"UGP2","display_label":"UGP2","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/12527"}],"genes":["UGP2"],"platforms":[],"platform":null,"publications":["PMID:31820119"],"publication_contexts":[{"context_id":"disorder:UGP2-Related_Developmental_and_Epileptic_Encephalopathy_83","publication":"PMID:31820119"}],"publication":"PMID:31820119","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/31820119","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:31820119","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/31820119","reference_title":"Loss of UGP2 in brain leads to a severe epileptic encephalopathy, emphasizing that bi-allelic isoform-specific start-loss mutations of essential genes can cause genetic diseases.","supports":"SUPPORT","evidence_source":"OTHER","snippet":"RNA-Seq of in vitro studies is publicly available through the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) under accession number GSE137129.","explanation":"The paper's data-availability statement identifies the accession."}],"notes":[],"contexts":[{"id":"disorder:UGP2-Related_Developmental_and_Epileptic_Encephalopathy_83","name":"UGP2-related developmental and epileptic encephalopathy 83","kind":"Disorder","source_path":"kb/disorders/UGP2-Related_Developmental_and_Epileptic_Encephalopathy_83.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/UGP2-Related_Developmental_and_Epileptic_Encephalopathy_83.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/UGP2-related_developmental_and_epileptic_encephalopathy_83.html#dataset-geo-gse137129"}],"context_names":["UGP2-related developmental and epileptic encephalopathy 83"],"disease_names":["UGP2-related developmental and epileptic encephalopathy 83"],"disease_name":"UGP2-related developmental and epileptic encephalopathy 83","same_context_model_ids":["model:kb/disorders/UGP2-Related_Developmental_and_Epileptic_Encephalopathy_83.yaml:UGP2-engineered and patient-derived neural stem-cell models"],"candidate_model_ids":["model:kb/disorders/UGP2-Related_Developmental_and_Epileptic_Encephalopathy_83.yaml:UGP2-engineered and patient-derived neural stem-cell models"],"association_basis":"Same publication as a NAM (candidate)","nam_disease_context":"Same publication as a NAM (candidate)","source_paths":["kb/disorders/UGP2-Related_Developmental_and_Epileptic_Encephalopathy_83.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/UGP2-Related_Developmental_and_Epileptic_Encephalopathy_83.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/UGP2-related_developmental_and_epileptic_encephalopathy_83.html#dataset-geo-gse137129"]},{"id":"dataset:geo:gse137420","accession":"geo:GSE137420","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE137420","title":"Synapse alterations precede neuronal damage and storage pathology in a human cerebral organoid  model of CLN3-Juvenile Neuronal Ceroid Lipofuscinosis","alternate_titles":[],"description":"We developed an invitro model for Juvenile Neuronal Ceroid Lipofuscinosis (JNCL) using isogenic CLN3 mutated human iPS cell lines and performed transcriptomic profiling of brain organoids derived from these lines to identify transcriptomic changes in the early developing brain model.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:31888773"],"publication_contexts":[{"context_id":"disorder:Neuronal_Ceroid_Lipofuscinosis","publication":"PMID:31888773"}],"publication":"PMID:31888773","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/31888773","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Neuronal Ceroid Lipofuscinosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Neuronal_Ceroid_Lipofuscinosis","name":"Neuronal Ceroid Lipofuscinosis","kind":"Disorder","source_path":"kb/disorders/Neuronal_Ceroid_Lipofuscinosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Neuronal_Ceroid_Lipofuscinosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Neuronal_Ceroid_Lipofuscinosis.html#dataset-geo-gse137420"}],"context_names":["Neuronal Ceroid Lipofuscinosis"],"disease_names":["Neuronal Ceroid Lipofuscinosis"],"disease_name":"Neuronal Ceroid Lipofuscinosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Neuronal_Ceroid_Lipofuscinosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Neuronal_Ceroid_Lipofuscinosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Neuronal_Ceroid_Lipofuscinosis.html#dataset-geo-gse137420"]},{"id":"dataset:geo:gse138167","accession":"geo:GSE138167","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE138167","title":"RNA sequencing of primary bronchial airway epithelial cells from young children with and without CF, including those with and without rhinovirus infection in vitro","alternate_titles":[],"description":"Early life viral infections are responsible for pulmonary exacerbations that can contribute to disease progression in young children with CF. The most common respiratory viruses detected in the CF airway are human rhinoviruses (RV) and susceptibility to infection has been attributed to dysregulated airway epithelial responses, although evidence has been conflicting. Here, we exposed airway epithelial cells from children with and without CF to RV in vitro. Using RNA-Seq, we profiled the transcriptomic differences of CF and non-CF airway epithelial cells at baseline and in response to RV. There were only modest differences between CF and non-CF cells at baseline.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[24],"sample_count":24,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:32765492"],"publication_contexts":[{"context_id":"disorder:Rhinovirus_Infection","publication":"PMID:32765492"}],"publication":"PMID:32765492","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32765492","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Rhinovirus Infection (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Rhinovirus_Infection","name":"Rhinovirus Infection","kind":"Disorder","source_path":"kb/disorders/Rhinovirus_Infection.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rhinovirus_Infection.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Rhinovirus_Infection.html#dataset-geo-gse138167"}],"context_names":["Rhinovirus Infection"],"disease_names":["Rhinovirus Infection"],"disease_name":"Rhinovirus Infection","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Rhinovirus_Infection.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rhinovirus_Infection.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Rhinovirus_Infection.html#dataset-geo-gse138167"]},{"id":"dataset:geo:gse138332","accession":"geo:GSE138332","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE138332","title":"Gut dysbiosis modulates the immune response to factor VIIII in murine hemophilia A","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["MULTI_OMICS"],"data_type_labels":["Multi Omics"],"data_type_label":"Multi Omics","organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[29],"sample_count":29,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:32556285"],"publication_contexts":[{"context_id":"disorder:Hemophilia_A","publication":"PMID:32556285"}],"publication":"PMID:32556285","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32556285","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Hemophilia A (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Hemophilia_A","name":"Hemophilia A","kind":"Disorder","source_path":"kb/disorders/Hemophilia_A.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hemophilia_A.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hemophilia_A.html#dataset-geo-gse138332"}],"context_names":["Hemophilia A"],"disease_names":["Hemophilia A"],"disease_name":"Hemophilia A","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hemophilia_A.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hemophilia_A.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hemophilia_A.html#dataset-geo-gse138332"]},{"id":"dataset:geo:gse138379","accession":"geo:GSE138379","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE138379","title":"Fibroblast-specific genome-scale modelling predicts an imbalance in amino acid metabolism in Refsum disease","alternate_titles":[],"description":"In this study, we reconstructed a fibroblast-specific genome-scale model based on the recently published, FAD-curated model, based on Recon3D reconstruction. To constrain the model we used transcriptomics, and proteomics data, which we obtained from healthy controls and Refsum disease patient fibroblasts incubated with phytol, a precursor of phytanic acid. Using this model, we investigated the metabolic phenotype of Refsum disease at the genome-scale, and we studied the effect of phytanic acid on cell metabolism. We identified 20 metabolites that were predicted to discriminate between Healthy and Refsum disease patients, several of which with a link to amino acid metabolism.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[96],"sample_count":96,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:32160399"],"publication_contexts":[{"context_id":"disorder:Adult_Refsum_Disease","publication":"PMID:32160399"}],"publication":"PMID:32160399","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32160399","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Adult Refsum Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Adult_Refsum_Disease","name":"Adult Refsum Disease","kind":"Disorder","source_path":"kb/disorders/Adult_Refsum_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Adult_Refsum_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Adult_Refsum_Disease.html#dataset-geo-gse138379"}],"context_names":["Adult Refsum Disease"],"disease_names":["Adult Refsum Disease"],"disease_name":"Adult Refsum Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Adult_Refsum_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Adult_Refsum_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Adult_Refsum_Disease.html#dataset-geo-gse138379"]},{"id":"dataset:geo:gse138852","accession":"geo:GSE138852","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE138852","title":"A single-cell atlas of the human cortex reveals drivers of transcriptional changes in Alzheimer's disease in specific cell subpopulations","alternate_titles":[],"description":"Human entorhinal cortex single-nucleus atlas resolving cell-subpopulation transcriptional change in Alzheimer disease.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"Homo sapiens","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0002728","label":"entorhinal cortex","display_label":"entorhinal cortex","url":"http://purl.obolibrary.org/obo/UBERON_0002728"}],"sample_type_labels":["entorhinal cortex"],"sample_counts":[8],"sample_count":8,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:31768052"],"publication_contexts":[{"context_id":"disorder:Alzheimer_Disease","publication":"PMID:31768052"}],"publication":"PMID:31768052","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/31768052","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Small donor count (8); curated as a replication cohort, not as a primary discovery set. Accession resolved against the GEO API with `just verify-datasets`."],"contexts":[{"id":"disorder:Alzheimer_Disease","name":"Alzheimer Disease","kind":"Disorder","source_path":"kb/disorders/Alzheimer_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alzheimer_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Alzheimer_Disease.html#dataset-geo-gse138852"}],"context_names":["Alzheimer Disease"],"disease_names":["Alzheimer Disease"],"disease_name":"Alzheimer Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Alzheimer_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alzheimer_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Alzheimer_Disease.html#dataset-geo-gse138852"]},{"id":"dataset:geo:gse138966","accession":"geo:GSE138966","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE138966","title":"Long non-coding RNA and mRNA transcriptomic profiles after ischemia-reperfusion injury in rat spinal cord.","alternate_titles":[],"description":"With the aim of exploring expression profiles and biological functions of long non-coding RNA (lncRNA) and mRNAs after ischemia-reperfusion injury (SCII), differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) in rat spinal cords were identified following SCII through high-throughput RNA sequencing. In total, 1455 lncRNAs and 6707 mRNAs were observed to be differentially expressed (FC ≥1.5 and P <0.05) after SCII, including 761 up-regulated and 694 down-regulated lncRNAs and, 3772 up-regulated and 2935 down-regulated mRNAs.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10116","label":"Rattus norvegicus","display_label":"rat","url":"http://purl.obolibrary.org/obo/NCBITaxon_10116"}],"organism_labels":["Rattus norvegicus"],"organism_label":"Rattus norvegicus","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:31934506"],"publication_contexts":[{"context_id":"disorder:Spinal_Cord_Ischemia","publication":"PMID:31934506"}],"publication":"PMID:31934506","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/31934506","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Spinal Cord Ischemia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Spinal_Cord_Ischemia","name":"Spinal Cord Ischemia","kind":"Disorder","source_path":"kb/disorders/Spinal_Cord_Ischemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Spinal_Cord_Ischemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Spinal_Cord_Ischemia.html#dataset-geo-gse138966"}],"context_names":["Spinal Cord Ischemia"],"disease_names":["Spinal Cord Ischemia"],"disease_name":"Spinal Cord Ischemia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Spinal_Cord_Ischemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Spinal_Cord_Ischemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Spinal_Cord_Ischemia.html#dataset-geo-gse138966"]},{"id":"dataset:geo:gse139181","accession":"geo:GSE139181","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE139181","title":"Transcriptomics analysis of trimester-specific full-term placentas from three Zika virus-infected women","alternate_titles":[],"description":"Effects of Zika virus (ZIKV) infection on placental development during pregnancy are unclear. In this study, full-term placentas from three women, each infected with ZIKV during specific pregnancy trimesters, were harvested for anatomic, immunologic and transcriptomic analysis. Each woman exhibited a unique immune response with raised IL-1RA, IP-10, EGF and RANTES expression, and neutrophil numbers during the acute infection phase. Although ZIKV NS3 antigens co-localized to placental Hofbauer cells, the placentas showed no anatomical defects.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[33],"sample_count":33,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:31709049"],"publication_contexts":[{"context_id":"disorder:Congenital_Zika_Syndrome","publication":"PMID:31709049"}],"publication":"PMID:31709049","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/31709049","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Congenital Zika Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Congenital_Zika_Syndrome","name":"Congenital Zika Syndrome","kind":"Disorder","source_path":"kb/disorders/Congenital_Zika_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Congenital_Zika_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Congenital_Zika_Syndrome.html#dataset-geo-gse139181"}],"context_names":["Congenital Zika Syndrome"],"disease_names":["Congenital Zika Syndrome"],"disease_name":"Congenital Zika Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Congenital_Zika_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Congenital_Zika_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Congenital_Zika_Syndrome.html#dataset-geo-gse139181"]},{"id":"dataset:geo:gse139365","accession":"geo:GSE139365","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE139365","title":"Gene expression analysis in primary cells derived from patients with Autosomal-dominant hyper-IgE syndrome (AD-HIES)","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[24],"sample_count":24,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:32369445"],"publication_contexts":[{"context_id":"disorder:Autosomal_Dominant_Hyper-IgE_Syndrome","publication":"PMID:32369445"}],"publication":"PMID:32369445","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32369445","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Autosomal Dominant Hyper-IgE Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Autosomal_Dominant_Hyper-IgE_Syndrome","name":"Autosomal Dominant Hyper-IgE Syndrome","kind":"Disorder","source_path":"kb/disorders/Autosomal_Dominant_Hyper-IgE_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autosomal_Dominant_Hyper-IgE_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Dominant_Hyper-IgE_Syndrome.html#dataset-geo-gse139365"}],"context_names":["Autosomal Dominant Hyper-IgE Syndrome"],"disease_names":["Autosomal Dominant Hyper-IgE Syndrome"],"disease_name":"Autosomal Dominant Hyper-IgE Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Autosomal_Dominant_Hyper-IgE_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autosomal_Dominant_Hyper-IgE_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Dominant_Hyper-IgE_Syndrome.html#dataset-geo-gse139365"]},{"id":"dataset:geo:gse139516","accession":"geo:GSE139516","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE139516","title":"Transcriptomic Analysis Of circRNAs/miRNAs/mRNAs upon Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection","alternate_titles":[],"description":"Human circular RNAs can function in competing endogenous RNA (ceRNA) network by sponging miRNA and regulating gene expression. Viruses are evolved to regulate noncoding RNAs such as miRNAs and circRNAs to facilitate their propagation and pathogenesis. Studies on how host ceRNAs upon human coronavirus infection were scarce, and the functions of circRNAs during the infection of Middle East respiratory syndrome coronavirus (MERS-CoV) has not been deeply revealed. Therefore, we conducted a whole transcriptional profile (RNA-seq) analysis to compare the expression of circRNAs, miRNAs and mRNAs between the mock-infected and MERS-CoV-infected human lung adenocarcinoma (Calu-3) cells.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[27],"sample_count":27,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:32223537"],"publication_contexts":[{"context_id":"disorder:Middle_East_Respiratory_Syndrome","publication":"PMID:32223537"}],"publication":"PMID:32223537","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32223537","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Middle East Respiratory Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Middle_East_Respiratory_Syndrome","name":"Middle East Respiratory Syndrome","kind":"Disorder","source_path":"kb/disorders/Middle_East_Respiratory_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Middle_East_Respiratory_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Middle_East_Respiratory_Syndrome.html#dataset-geo-gse139516"}],"context_names":["Middle East Respiratory Syndrome"],"disease_names":["Middle East Respiratory Syndrome"],"disease_name":"Middle East Respiratory Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Middle_East_Respiratory_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Middle_East_Respiratory_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Middle_East_Respiratory_Syndrome.html#dataset-geo-gse139516"]},{"id":"dataset:geo:gse139535","accession":"geo:GSE139535","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE139535","title":"Single Cell Sequencing Analysis for Wolfram Syndrome (WS4) Unedited and Corrected Stem Cell-Derived Beta Cells","alternate_titles":[],"description":"Single-cell transcriptomic comparison of unedited Wolfram patient stem-cell-derived beta cells and CRISPR-corrected isogenic beta cells, directly linked to the genetic-rescue experimental model in this entry.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[2],"sample_count":2,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:32846125"],"publication_contexts":[{"context_id":"disorder:Wolfram_Syndrome","publication":"PMID:32846125"}],"publication":"PMID:32846125","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32846125","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Accession, title, organism, sequencing type, and two GEO samples were verified against NCBI GEO on 2026-08-19. GEO metadata links this accession to PMID:32846125, the stem-cell-derived islet maturation study. The disease-specific CRISPR-correction report (PMID:32321868) describes the WS4corr model but is not the publication assigned to this GEO record."],"contexts":[{"id":"disorder:Wolfram_Syndrome","name":"Wolfram Syndrome","kind":"Disorder","source_path":"kb/disorders/Wolfram_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Wolfram_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Wolfram_Syndrome.html#dataset-geo-gse139535"}],"context_names":["Wolfram Syndrome"],"disease_names":["Wolfram Syndrome"],"disease_name":"Wolfram Syndrome","same_context_model_ids":["model:kb/disorders/Wolfram_Syndrome.yaml:CISD2-knockout human iPSC-derived cortical neurons","model:kb/disorders/Wolfram_Syndrome.yaml:CRISPR-corrected patient iPSC-derived beta cells"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Wolfram_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Wolfram_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Wolfram_Syndrome.html#dataset-geo-gse139535"]},{"id":"dataset:geo:gse139965","accession":"geo:GSE139965","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE139965","title":"Drug repurposing of bromodomain inhibitors as potential novel therapeutic leads for lymphatic filariasis guided by multi-species transcriptomics","alternate_titles":[],"description":"Brugia malayi, Wolbachia (wBm), and Aedes aegypti transcriptome reads from across the B. malayi FR3 life cycle","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[81],"sample_count":81,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:31796568"],"publication_contexts":[{"context_id":"disorder:Lymphatic_Filariasis","publication":"PMID:31796568"}],"publication":"PMID:31796568","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/31796568","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Lymphatic filariasis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Lymphatic_Filariasis","name":"Lymphatic filariasis","kind":"Disorder","source_path":"kb/disorders/Lymphatic_Filariasis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Lymphatic_Filariasis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Lymphatic_filariasis.html#dataset-geo-gse139965"}],"context_names":["Lymphatic filariasis"],"disease_names":["Lymphatic filariasis"],"disease_name":"Lymphatic filariasis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Lymphatic_Filariasis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Lymphatic_Filariasis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Lymphatic_filariasis.html#dataset-geo-gse139965"]},{"id":"dataset:geo:gse140390","accession":"geo:GSE140390","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE140390","title":"Detection of tetraploidization in chromophobe renal cell carcinoma: insights and pitfalls [Affymetrix OncoScan_CNV]","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[25],"sample_count":25,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["GEO series matched because chromophobe renal cell carcinoma is named in the dataset's own title. Directly relevant to the open question recorded in the chrcc_hypodiploidy_versus_gains discussion, since it addresses genome doubling on top of the baseline loss pattern. Relevance confirmed manually; retrieved 2026-08-15."],"contexts":[{"id":"disorder:Chromophobe_Renal_Cell_Carcinoma","name":"Chromophobe Renal Cell Carcinoma","kind":"Disorder","source_path":"kb/disorders/Chromophobe_Renal_Cell_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chromophobe_Renal_Cell_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chromophobe_Renal_Cell_Carcinoma.html#dataset-geo-gse140390"}],"context_names":["Chromophobe Renal Cell Carcinoma"],"disease_names":["Chromophobe Renal Cell Carcinoma"],"disease_name":"Chromophobe Renal Cell Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chromophobe_Renal_Cell_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chromophobe_Renal_Cell_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chromophobe_Renal_Cell_Carcinoma.html#dataset-geo-gse140390"]},{"id":"dataset:geo:gse140415","accession":"geo:GSE140415","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE140415","title":"OncoScan CNV Assay (Thermo Fisher Scientific/Affymetrix) data for 13 cold agglutinin disease samples","alternate_titles":[],"description":"Copy-number profiling of 13 primary cold agglutinin disease samples by SNP array. Trisomy 3 or partial 3q was present in 12 of 13 cases, and trisomy 12 or trisomy 18 (never both) in 9 of 13 — the cytogenetic counterpart of the recurrent somatic mutation profile recorded in this entry's `genetic:` section.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[13],"sample_count":13,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["OncoScan CNV Assay (Thermo Fisher Scientific/Affymetrix)"],"platform":"OncoScan CNV Assay (Thermo Fisher Scientific/Affymetrix)","publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE140415","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE140415","reference_title":null,"supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"In 12/13 cases complete or partial trisomy 3/3q was detected.","explanation":"The repository's own summary reports near-universal trisomy 3/3q in primary CAD samples, which is the finding this dataset record is curated for."}],"notes":["The only DIRECT candidate returned by `just discover-datasets Cold_Agglutinin_Disease`; the eleven GENE_ONLY candidates were rejected on relevance triage, since they matched on KMT2D, CARD11 or CXCR4 in unrelated diseases (B-cell lymphoma, colorectal cancer, HIV host factors, neurodevelopmental disorders) rather than on cold agglutinin disease."],"contexts":[{"id":"disorder:Cold_Agglutinin_Disease","name":"Cold Agglutinin Disease","kind":"Disorder","source_path":"kb/disorders/Cold_Agglutinin_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cold_Agglutinin_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cold_Agglutinin_Disease.html#dataset-geo-gse140415"}],"context_names":["Cold Agglutinin Disease"],"disease_names":["Cold Agglutinin Disease"],"disease_name":"Cold Agglutinin Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cold_Agglutinin_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cold_Agglutinin_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cold_Agglutinin_Disease.html#dataset-geo-gse140415"]},{"id":"dataset:geo:gse140732","accession":"geo:GSE140732","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE140732","title":"A Highly Phenotyped Open Access Repository of Alpha-1 Antitrypsin Deficiency Pluripotent Stem Cells","alternate_titles":[],"description":"We profiled the global transcriptomes of 10 featured AATD-patient specific iPSC that underwent directed differentiation towards a hepatic and lung lineage. We used digital gene expression (DGE), a platform for high-fidelity RNA sequencing, and in addition to differentiated iPSC-derived cell types mentioned above (iHeps and iPSC-Lung progenitors), we also collected RNA from undifferentiated iPSCs and from a panel of primary adult human hepatocytes (PHH) for comparison.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[96],"sample_count":96,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:32619491"],"publication_contexts":[{"context_id":"disorder:Alpha_1_Antitrypsin_Deficiency","publication":"PMID:32619491"}],"publication":"PMID:32619491","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32619491","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Alpha-1 Antitrypsin Deficiency (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Alpha_1_Antitrypsin_Deficiency","name":"Alpha-1 Antitrypsin Deficiency","kind":"Disorder","source_path":"kb/disorders/Alpha_1_Antitrypsin_Deficiency.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alpha_1_Antitrypsin_Deficiency.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Alpha-1_Antitrypsin_Deficiency.html#dataset-geo-gse140732"}],"context_names":["Alpha-1 Antitrypsin Deficiency"],"disease_names":["Alpha-1 Antitrypsin Deficiency"],"disease_name":"Alpha-1 Antitrypsin Deficiency","same_context_model_ids":["model:kb/disorders/Alpha_1_Antitrypsin_Deficiency.yaml:CRISPR-engineered Huh7.5Z hepatocyte cell line"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Alpha_1_Antitrypsin_Deficiency.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alpha_1_Antitrypsin_Deficiency.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Alpha-1_Antitrypsin_Deficiency.html#dataset-geo-gse140732"]},{"id":"dataset:geo:gse140965","accession":"geo:GSE140965","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE140965","title":"Transcriptome study of MYBPC3 loss of function mutations","alternate_titles":[],"description":"Isogenic human iPSC-cardiomyocytes carrying heterozygous MYBPC3 loss-of-function edits (promoter deletion, start-site deletion, exon 27 frameshift) alongside a homozygous exon 27 frameshift. The allelic-dose contrast this entry turns on, in one human genetic background.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[30],"sample_count":30,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:7551","label":"MYBPC3","display_label":"MYBPC3","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/7551"}],"genes":["MYBPC3"],"platforms":[],"platform":null,"publications":["PMID:31877118"],"publication_contexts":[{"context_id":"disorder:Left_Ventricular_Noncompaction_10","publication":"PMID:31877118"}],"publication":"PMID:31877118","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/31877118","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE140965","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE140965","reference_title":"Transcriptome study of MYBPC3 loss of function mutations","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Induced pluripotent stem cells were gene edited to introduce heterozygous (promoter deletion, start site deletion, and exon 27 frameshift) and homozygous (exon 27 frameshift) mutations.","explanation":"Establishes that the design holds genetic background fixed and varies MYBPC3 allelic dose, which is the comparison the dose-dependence nodes in this entry assert."}],"notes":["Engineered rather than patient-derived, and the readout is transcriptomic in two-dimensional cardiomyocytes, so it cannot address ventricular compaction. Relevant to whether the mono- and bi-allelic states differ in kind or only in degree."],"contexts":[{"id":"disorder:Left_Ventricular_Noncompaction_10","name":"Left Ventricular Noncompaction 10","kind":"Disorder","source_path":"kb/disorders/Left_Ventricular_Noncompaction_10.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Left_Ventricular_Noncompaction_10.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Left_Ventricular_Noncompaction_10.html#dataset-geo-gse140965"}],"context_names":["Left Ventricular Noncompaction 10"],"disease_names":["Left Ventricular Noncompaction 10"],"disease_name":"Left Ventricular Noncompaction 10","same_context_model_ids":["model:kb/disorders/Left_Ventricular_Noncompaction_10.yaml:Biallelic MYBPC3 truncating hiPSC line with isogenic control","model:kb/disorders/Left_Ventricular_Noncompaction_10.yaml:Isogenic hiPSC-cardiomyocytes carrying MYBPC3 premature termination codon variants"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Left_Ventricular_Noncompaction_10.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Left_Ventricular_Noncompaction_10.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Left_Ventricular_Noncompaction_10.html#dataset-geo-gse140965"]},{"id":"dataset:geo:gse141578","accession":"geo:GSE141578","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE141578","title":"CD4+ T cells contribute to neurodegeneration in Lewy body dementia [CSF_and_PBMCs_Healthy and LBD]","alternate_titles":[],"description":"Recent studies indicate that the adaptive immune system plays a role in Lewy body dementia (LBD). However, the mechanism regulating T cell brain homing in LBD is unknown. Here, we observed T cells adjacent to Lewy bodies and dopaminergic neurons in post-mortem LBD brains. Single-cell RNA sequencing of cerebrospinal fluid (CSF) identified upregulated expression of C-X-C Motif Chemokine Receptor 4 (CXCR4) in CD4+ T cells in LBD. CSF protein levels of the CXCR4 ligand, C-X-C Motif Chemokine Ligand 12 (CXCL12) were associated with neuroaxonal damage in LBD.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[35],"sample_count":35,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:34648304"],"publication_contexts":[{"context_id":"disorder:Dementia_with_Lewy_Bodies","publication":"PMID:34648304"}],"publication":"PMID:34648304","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34648304","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Dementia with Lewy Bodies (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Dementia_with_Lewy_Bodies","name":"Dementia with Lewy Bodies","kind":"Disorder","source_path":"kb/disorders/Dementia_with_Lewy_Bodies.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dementia_with_Lewy_Bodies.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Dementia_with_Lewy_Bodies.html#dataset-geo-gse141578"}],"context_names":["Dementia with Lewy Bodies"],"disease_names":["Dementia with Lewy Bodies"],"disease_name":"Dementia with Lewy Bodies","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association 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recorded","findings":[],"findings_text":[],"evidence":[{"reference":"url:https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE142599","reference_url":null,"reference_title":"GEO Accession viewer","supports":"SUPPORT","evidence_source":"OTHER","snippet":"Total RNA from casper, JAK1-WT and JAK1-A634D zebrafish embryos at 28 and 36 hours post-fertilization was extracted to characterize the transcriptomic effects of the JAK1-A634D gain-of-function mutation","explanation":"The GEO record states the model groups, time points, and transcriptomic study design."},{"reference":"url:https://www.ebi.ac.uk/europepmc/webservices/rest/PMC9869972/fullTextXML","reference_url":null,"reference_title":"Abstract","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"The zebrafish RNA-Seq data are available under","explanation":"The primary publication identifies the public accession for the zebrafish RNA-seq data."}],"notes":[],"contexts":[{"id":"disorder:Autoinflammation_Immune_Dysregulation_and_Eosinophilia","name":"Autoinflammation, immune dysregulation, and eosinophilia","kind":"Disorder","source_path":"kb/disorders/Autoinflammation_Immune_Dysregulation_and_Eosinophilia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autoinflammation_Immune_Dysregulation_and_Eosinophilia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autoinflammation,_immune_dysregulation,_and_eosinophilia.html#dataset-geo-gse142599"}],"context_names":["Autoinflammation, immune dysregulation, and eosinophilia"],"disease_names":["Autoinflammation, immune dysregulation, and eosinophilia"],"disease_name":"Autoinflammation, immune dysregulation, and eosinophilia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association 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The Illumina Infinium MethylationEPIC BeadChip was used, investigating app. 850,000 CpG sites throughout the genome","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[156],"sample_count":156,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:32151281"],"publication_contexts":[{"context_id":"disorder:Multiple_System_Atrophy","publication":"PMID:32151281"}],"publication":"PMID:32151281","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32151281","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Multiple System Atrophy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Multiple_System_Atrophy","name":"Multiple System Atrophy","kind":"Disorder","source_path":"kb/disorders/Multiple_System_Atrophy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Multiple_System_Atrophy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Multiple_System_Atrophy.html#dataset-geo-gse143157"}],"context_names":["Multiple System Atrophy"],"disease_names":["Multiple System Atrophy"],"disease_name":"Multiple System Atrophy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Multiple_System_Atrophy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Multiple_System_Atrophy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Multiple_System_Atrophy.html#dataset-geo-gse143157"]},{"id":"dataset:geo:gse144046","accession":"geo:GSE144046","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE144046","title":"Autism-linked Cullin3 germline haploinsufficiency severely impacts mouse brain development and cortical neurogenesis through RhoA signaling","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"house mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[108],"sample_count":108,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:2553","label":"CUL3","display_label":"CUL3","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/2553"}],"genes":["CUL3"],"platforms":[],"platform":null,"publications":["PMID:33727673"],"publication_contexts":[{"context_id":"disorder:Neurodevelopmental_Disorder_With_or_Without_Autism_or_Seizures","publication":"PMID:33727673"}],"publication":"PMID:33727673","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/33727673","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Spatiotemporal transcriptomic profiling of embryonic, early postnatal and adult brain from the CRISPR-generated Cul3 haploinsufficient mouse curated in animal_models. This is the underlying data for the neurogenesis and cytoskeletal findings and for the RhoA rescue. Relevance was triaged manually: a gene-symbol search on CUL3 returns mostly lung, yeast and 16p11.2/KCTD13 datasets that share the gene but not the disease, and those were rejected; this record was accepted because the series title, its linked publication and its genotype all name Cul3 haploinsufficiency in brain. Carries no evidence block by design - a GEO series has no abstract to quote exactly."],"contexts":[{"id":"disorder:Neurodevelopmental_Disorder_With_or_Without_Autism_or_Seizures","name":"Neurodevelopmental Disorder With or Without Autism or Seizures","kind":"Disorder","source_path":"kb/disorders/Neurodevelopmental_Disorder_With_or_Without_Autism_or_Seizures.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Neurodevelopmental_Disorder_With_or_Without_Autism_or_Seizures.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Neurodevelopmental_Disorder_With_or_Without_Autism_or_Seizures.html#dataset-geo-gse144046"}],"context_names":["Neurodevelopmental Disorder With or Without Autism or Seizures"],"disease_names":["Neurodevelopmental Disorder With or Without Autism or Seizures"],"disease_name":"Neurodevelopmental Disorder With or Without Autism or 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NAM","source_paths":["kb/disorders/Neurodevelopmental_Disorder_With_or_Without_Autism_or_Seizures.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Neurodevelopmental_Disorder_With_or_Without_Autism_or_Seizures.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Neurodevelopmental_Disorder_With_or_Without_Autism_or_Seizures.html#dataset-geo-gse144046"]},{"id":"dataset:geo:gse144847","accession":"geo:GSE144847","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE144847","title":"Transcriptome profile of Bbs8/TTC8 Knockout mouse RPE Tissue","alternate_titles":[],"description":"GEO SuperSeries containing P11 and P29 Bbs8-knockout versus wild-type mouse RPE expression studies (subseries GSE144845 and GSE144846), associated with the published RPE transcriptomic and proteomic analysis.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":["Bbs8 knockout retinal pigment epithelium","Wild-type retinal pigment epithelium"],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"MGI:1924290","label":"Bbs8","display_label":"Bbs8","url":null}],"genes":["Bbs8"],"platforms":[],"platform":null,"publications":["PMID:33681195"],"publication_contexts":[{"context_id":"disorder:BBSome-Related_Retinitis_Pigmentosa","publication":"PMID:33681195"}],"publication":"PMID:33681195","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/33681195","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:33681195","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33681195","reference_title":"Loss of Ciliary Gene Bbs8 Results in Physiological Defects in the Retinal Pigment Epithelium.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"We demonstrate that upon loss of Bbs8, predominantly thought to be a ciliary gene, the RPE shows changes in gene and protein expression initially involved in signaling pathways and developmental processes","explanation":"Describes molecular profiling of Bbs8-deficient retinal pigment epithelium."}],"notes":[],"contexts":[{"id":"disorder:BBSome-Related_Retinitis_Pigmentosa","name":"BBSome-related retinitis pigmentosa","kind":"Disorder","source_path":"kb/disorders/BBSome-Related_Retinitis_Pigmentosa.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/BBSome-Related_Retinitis_Pigmentosa.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/BBSome-related_retinitis_pigmentosa.html#dataset-geo-gse144847"}],"context_names":["BBSome-related retinitis pigmentosa"],"disease_names":["BBSome-related retinitis pigmentosa"],"disease_name":"BBSome-related retinitis pigmentosa","same_context_model_ids":["model:kb/disorders/BBSome-Related_Retinitis_Pigmentosa.yaml:IBMS-iPSC-063-06 BBS2 patient-derived induced pluripotent stem cell line","model:kb/disorders/BBSome-Related_Retinitis_Pigmentosa.yaml:KCi001-A BBS1 patient-derived induced pluripotent stem cell line"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/BBSome-Related_Retinitis_Pigmentosa.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/BBSome-Related_Retinitis_Pigmentosa.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/BBSome-related_retinitis_pigmentosa.html#dataset-geo-gse144847"]},{"id":"dataset:geo:gse145069","accession":"geo:GSE145069","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE145069","title":"Differential gene expression and pathway analysis by RNA sequencing in human OPTN(E50K) retinal ganglion cells","alternate_titles":[],"description":"RNA-seq of human pluripotent stem cell-derived retinal ganglion cells carrying the OPTN(E50K) mutation versus isogenic controls. Genotype- and cell-type-specific for this entity: the disease allele in the disease cell type, in a human system.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[8],"sample_count":8,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:32531194"],"publication_contexts":[{"context_id":"disorder:OPTN-related_Open_Angle_Glaucoma","publication":"PMID:32531194"}],"publication":"PMID:32531194","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32531194","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located by GEO DataSets search on \"optineurin E50K\" rather than on the disease name; accession, title, sample count and organism are GEO's own values, retrieved 2026-08-20. Relevance triage: this is one of only two accessions found that are specific to the OPTN(E50K) genotype rather than to glaucoma generally - a disease-name search returns trabecular meshwork and generic POAG datasets that resolve perfectly but are about the wrong entity. Carries no evidence block: an evidence item needs an exact quote from the cited abstract, and this record's provenance is the repository metadata plus its own linked publication."],"contexts":[{"id":"disorder:OPTN-related_Open_Angle_Glaucoma","name":"OPTN-related Open Angle Glaucoma","kind":"Disorder","source_path":"kb/disorders/OPTN-related_Open_Angle_Glaucoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/OPTN-related_Open_Angle_Glaucoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/OPTN-related_Open_Angle_Glaucoma.html#dataset-geo-gse145069"}],"context_names":["OPTN-related Open Angle Glaucoma"],"disease_names":["OPTN-related Open Angle Glaucoma"],"disease_name":"OPTN-related Open Angle Glaucoma","same_context_model_ids":["model:kb/disorders/OPTN-related_Open_Angle_Glaucoma.yaml:Isogenic OPTN(E50K) human pluripotent stem cell-derived retinal ganglion cells"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/OPTN-related_Open_Angle_Glaucoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/OPTN-related_Open_Angle_Glaucoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/OPTN-related_Open_Angle_Glaucoma.html#dataset-geo-gse145069"]},{"id":"dataset:geo:gse145102","accession":"geo:GSE145102","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE145102","title":"Astrocyte deletion of alpha2-Na/K ATPase triggers episodic motor paralysis in mice via a metabolic pathway","alternate_titles":[],"description":"Mouse transcriptomic resource from an ATP1A2-related aura-relevant model capturing brain metabolic and glial perturbation linked to migraine aura susceptibility.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[{"id":"UBERON:0000955","label":"brain","display_label":"brain tissue","url":"http://purl.obolibrary.org/obo/UBERON_0000955"}],"sample_type_labels":["brain"],"sample_counts":[28],"sample_count":28,"conditions":["ATP1A2-related migraine aura model","control brain tissue"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["GEO summary indicates a mouse aura-related Na/K ATPase model with transcriptomic profiling relevant to glial and metabolic mechanisms."],"contexts":[{"id":"disorder:Migraine_with_Aura","name":"Migraine with aura","kind":"Disorder","source_path":"kb/disorders/Migraine_with_Aura.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Migraine_with_Aura.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Migraine_with_aura.html#dataset-geo-gse145102"}],"context_names":["Migraine with aura"],"disease_names":["Migraine with aura"],"disease_name":"Migraine with aura","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Migraine_with_Aura.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Migraine_with_Aura.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Migraine_with_aura.html#dataset-geo-gse145102"]},{"id":"dataset:geo:gse145115","accession":"geo:GSE145115","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE145115","title":"Inhibition of the SUV4-20 H1 histone methyltransferase increases frataxin expression in Friedreich’s ataxia patient cells","alternate_titles":[],"description":"Genome-wide expression profiling of FRDA patient cells treated with the SUV4-20 methyltransferase inhibitor A-196, assessing FXN reactivation and off-target transcriptome perturbation.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[24],"sample_count":24,"conditions":["FRDA patient cells, A-196 treated","FRDA patient cells, untreated"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:33028632"],"publication_contexts":[{"context_id":"disorder:Friedreich_Ataxia","publication":"PMID:33028632"}],"publication":"PMID:33028632","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/33028632","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE145115","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE145115","reference_title":"Inhibition of the SUV4-20 H1 histone methyltransferase increases frataxin expression in Friedreich’s ataxia patient cells","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"In several FRDA cell lines and patient-derived primary peripheral blood mononuclear cells, A-196 increased FXN expression by up to 2-fold, an effect not seen in WT cells.","explanation":"The GEO summary describes the FXN-reactivation effect this expression series was generated to characterize."}],"notes":[],"contexts":[{"id":"disorder:Friedreich_Ataxia","name":"Friedreich Ataxia","kind":"Disorder","source_path":"kb/disorders/Friedreich_Ataxia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Friedreich_Ataxia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Friedreich_Ataxia.html#dataset-geo-gse145115"}],"context_names":["Friedreich Ataxia"],"disease_names":["Friedreich Ataxia"],"disease_name":"Friedreich Ataxia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Friedreich_Ataxia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Friedreich_Ataxia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Friedreich_Ataxia.html#dataset-geo-gse145115"]},{"id":"dataset:geo:gse145836","accession":"geo:GSE145836","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE145836","title":"Human retinal Mueller glial cell (HMG) response to Toxoplasma gondii infection","alternate_titles":[],"description":"Transcriptomic profiling of primary human retinal Mueller glial cells infected with Toxoplasma gondii, relevant to the retinal arm of this entry's pathograph (Recurrent Necrotizing Retinochoroiditis).","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[36],"sample_count":36,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified via `just discover-datasets Toxoplasmosis` (DIRECT relevance tier) and confirmed with `just verify-datasets`. No evidence block: a bulk-discovered accession has no abstract quote to anchor an evidence item."],"contexts":[{"id":"disorder:Toxoplasmosis","name":"Toxoplasmosis","kind":"Disorder","source_path":"kb/disorders/Toxoplasmosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Toxoplasmosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Toxoplasmosis.html#dataset-geo-gse145836"}],"context_names":["Toxoplasmosis"],"disease_names":["Toxoplasmosis"],"disease_name":"Toxoplasmosis","same_context_model_ids":["model:kb/disorders/Toxoplasmosis.yaml:Human cell culture single-cell transcriptomics of ROP/GRA effector injection","model:kb/disorders/Toxoplasmosis.yaml:Stress-induced bradyzoite differentiation in cell culture"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Toxoplasmosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Toxoplasmosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Toxoplasmosis.html#dataset-geo-gse145836"]},{"id":"dataset:geo:gse145966","accession":"geo:GSE145966","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE145966","title":"Disruption of Nipbl/Scc2 in Cornelia de Lange Syndrome provokes cohesin genome-wide redistribution with an impact in the transcriptome","alternate_titles":[],"description":"Cornelia de Lange syndrome (CdLS) is a rare disease affecting multiple organs and systems during development. Mutations in the cohesin loader, Nipbl/Scc2 were first described and are the most frequent in clinically diagnosed CdLS patients. The molecular mechanism driving the CdLS phenotypes are not understood. Apart from its canonical role in sister chromatid cohesion, cohesin has also been involved in the regulation of the spatial organization of the genome.","alternate_descriptions":[],"data_types":["CHIP_SEQ"],"data_type_labels":["Chromatin immunoprecipitation sequencing"],"data_type_label":"Chromatin immunoprecipitation sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[10],"sample_count":10,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:34315879"],"publication_contexts":[{"context_id":"disorder:Cornelia_de_Lange_Syndrome","publication":"PMID:34315879"}],"publication":"PMID:34315879","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34315879","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Cornelia de Lange syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Cornelia_de_Lange_Syndrome","name":"Cornelia de Lange syndrome","kind":"Disorder","source_path":"kb/disorders/Cornelia_de_Lange_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cornelia_de_Lange_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cornelia_de_Lange_syndrome.html#dataset-geo-gse145966"}],"context_names":["Cornelia de Lange syndrome"],"disease_names":["Cornelia de Lange syndrome"],"disease_name":"Cornelia de Lange syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cornelia_de_Lange_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cornelia_de_Lange_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cornelia_de_Lange_syndrome.html#dataset-geo-gse145966"]},{"id":"dataset:geo:gse1462","accession":"geo:GSE1462","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE1462","title":"Mitochondrial disorders","alternate_titles":[],"description":"Affymetrix expression profiling of skeletal-muscle biopsies from twelve patients with mitochondrial encephalomyopathy - four with the common 4977 bp mtDNA deletion and eight carrying m.3243A>G, the latter split evenly between progressive external ophthalmoplegia and MELAS phenotypes - against age-matched controls.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[15],"sample_count":15,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:15728662"],"publication_contexts":[{"context_id":"disorder:MELAS_Syndrome","publication":"PMID:15728662"}],"publication":"PMID:15728662","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/15728662","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:15728662","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/15728662","reference_title":"Skeletal muscle gene expression profiling in mitochondrial disorders.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"the differential expression profile of MELAS(A3243G) vs. PEO(A3243G) may support a role of nuclear background in contributing to these different clinical phenotypes","explanation":"A patient-tissue contrast with the mtDNA genotype held fixed, nominating nuclear background as the modifier behind divergent m.3243A>G phenotypes."},{"reference":"PMID:15728662","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/15728662","reference_title":"Skeletal muscle gene expression profiling in mitochondrial disorders.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"the clinical phenotype is not simply a direct consequence of the relative abundance of mutated mtDNA. Other factors, such as nuclear background, can contribute to the disease process, resulting in a wide range of phenotypes caused by the same mutation","explanation":"States the premise of the genotype-phenotype gap and the modifier hypothesis this dataset was built to test."}],"notes":["The only dataset in this entry that holds genotype constant and varies clinical phenotype in patient tissue: four PEO and four MELAS patients, all m.3243A>G, all muscle. That design isolates the modifier question the genotype-phenotype gap turns on, and the authors read their result as support for nuclear background as the modifier. Four patients per arm on a 2005 array platform, so it is a hypothesis, not a demonstration - but it is the right experiment. Note this record is easy to mis-triage: its GEO title is the uninformative \"Mitochondrial disorders\" and summary-level screening reads it as a mixed-genotype cohort rather than a matched-genotype phenotype contrast."],"contexts":[{"id":"disorder:MELAS_Syndrome","name":"MELAS Syndrome","kind":"Disorder","source_path":"kb/disorders/MELAS_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MELAS_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/MELAS_Syndrome.html#dataset-geo-gse1462"}],"context_names":["MELAS Syndrome"],"disease_names":["MELAS Syndrome"],"disease_name":"MELAS Syndrome","same_context_model_ids":["model:kb/disorders/MELAS_Syndrome.yaml:m.3243A>G patient iPSC-derived neurons"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/MELAS_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MELAS_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/MELAS_Syndrome.html#dataset-geo-gse1462"]},{"id":"dataset:geo:gse146207","accession":"geo:GSE146207","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE146207","title":"Coordination of mRNA and tRNA methylations by TRMT10A","alternate_titles":[],"description":"The dataset underlying the TRMT10A-FTO study, profiling m6A changes and transcript-level consequences of TRMT10A ablation. Supports the \"Coordinated mRNA m6A Dysregulation via the FTO Axis\" node and is the most directly testable resource for the open question of what drives peripheral insulin resistance in this disorder.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:28403","label":"TRMT10A","display_label":"TRMT10A","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/28403"}],"genes":["TRMT10A"],"platforms":[],"platform":null,"publications":["PMID:32213595"],"publication_contexts":[{"context_id":"disorder:Microcephaly_Short_Stature_and_Impaired_Glucose_Metabolism_1","publication":"PMID:32213595"}],"publication":"PMID:32213595","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32213595","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Surfaced by `just discover-datasets` as a GENE_ONLY candidate; retained because its linked publication (PMID:32213595) is already cited in this entry for the FTO/m6A mechanism, so the disease relevance is established rather than assumed. GEO does not assign a single gdstype to this series, so `data_type` is left unset rather than guessed. A cell-line perturbation dataset, not patient material."],"contexts":[{"id":"disorder:Microcephaly_Short_Stature_and_Impaired_Glucose_Metabolism_1","name":"Microcephaly, Short Stature, and Impaired Glucose Metabolism 1","kind":"Disorder","source_path":"kb/disorders/Microcephaly_Short_Stature_and_Impaired_Glucose_Metabolism_1.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Microcephaly_Short_Stature_and_Impaired_Glucose_Metabolism_1.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Microcephaly,_Short_Stature,_and_Impaired_Glucose_Metabolism_1.html#dataset-geo-gse146207"}],"context_names":["Microcephaly, Short Stature, and Impaired Glucose Metabolism 1"],"disease_names":["Microcephaly, Short Stature, and Impaired Glucose Metabolism 1"],"disease_name":"Microcephaly, Short Stature, and Impaired Glucose Metabolism 1","same_context_model_ids":["model:kb/disorders/Microcephaly_Short_Stature_and_Impaired_Glucose_Metabolism_1.yaml:Patient-derived iPSC beta-like cells (TRMT10A-deficient)","model:kb/disorders/Microcephaly_Short_Stature_and_Impaired_Glucose_Metabolism_1.yaml:TRMT10A silencing in rat INS-1E and human EndoC-betaH1 beta cells"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Microcephaly_Short_Stature_and_Impaired_Glucose_Metabolism_1.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Microcephaly_Short_Stature_and_Impaired_Glucose_Metabolism_1.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Microcephaly,_Short_Stature,_and_Impaired_Glucose_Metabolism_1.html#dataset-geo-gse146207"]},{"id":"dataset:geo:gse146212","accession":"geo:GSE146212","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE146212","title":"Severe hydroxymethylbilane synthase deficiency causes depression-like behavior and mitochondrial dysfunction in a mouse model of homozygous dominant acute intermittent porphyria","alternate_titles":[],"description":"Acute intermittent porphyria (AIP) is an autosomal dominant inborn error of heme biosynthesis due to a pathogenic mutation in the Hmbs gene, resulting in half-normal activity of hydroxymethylbilane synthase. Factors that induce hepatic heme biosynthesis induce episodic attacks in heterozygous patients. The clinical presentation of acute attacks involves the signature neurovisceral pain and may include psychiatric symptoms. Here we used a knock-in mouse line that is biallelic for the Hmbs c.500G>A (p.R167Q) mutation with ~5% of normal hydroxymethylbilane synthase activity to unravel the consequences of severe HMBS deficiency on affective behavior and brain physiology.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:32197664"],"publication_contexts":[{"context_id":"disorder:Acute_Intermittent_Porphyria","publication":"PMID:32197664"}],"publication":"PMID:32197664","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32197664","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Acute Intermittent Porphyria (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Acute_Intermittent_Porphyria","name":"Acute Intermittent Porphyria","kind":"Disorder","source_path":"kb/disorders/Acute_Intermittent_Porphyria.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Acute_Intermittent_Porphyria.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Acute_Intermittent_Porphyria.html#dataset-geo-gse146212"}],"context_names":["Acute Intermittent Porphyria"],"disease_names":["Acute Intermittent Porphyria"],"disease_name":"Acute Intermittent Porphyria","same_context_model_ids":["model:kb/disorders/Acute_Intermittent_Porphyria.yaml:ALA exposure of human and rat cortical synaptic membranes","model:kb/disorders/Acute_Intermittent_Porphyria.yaml:Porphyrin-precursor exposure of human proximal tubular cells"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Acute_Intermittent_Porphyria.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Acute_Intermittent_Porphyria.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Acute_Intermittent_Porphyria.html#dataset-geo-gse146212"]},{"id":"dataset:geo:gse146621","accession":"geo:GSE146621","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE146621","title":"Distinct cardiac transcriptomic clustering in titin and lamin a/c-associated dilated cardiomyopathy patients","alternate_titles":[],"description":"RNA profiles strongly differ in TTNtv and LMNA-mutated DCM patients, despite clinical similarities as other pathogenic variant carriers such as RBM20 and MYH7, suggesting a specific genetic effect on the cardiac transcriptome in addition to the effect of the clinical component.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[29],"sample_count":29,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:32955937"],"publication_contexts":[{"context_id":"disorder:Dilated_Cardiomyopathy","publication":"PMID:32955937"}],"publication":"PMID:32955937","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32955937","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Dilated Cardiomyopathy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Dilated_Cardiomyopathy","name":"Dilated Cardiomyopathy","kind":"Disorder","source_path":"kb/disorders/Dilated_Cardiomyopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dilated_Cardiomyopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy.html#dataset-geo-gse146621"}],"context_names":["Dilated Cardiomyopathy"],"disease_names":["Dilated Cardiomyopathy"],"disease_name":"Dilated Cardiomyopathy","same_context_model_ids":["model:kb/disorders/Dilated_Cardiomyopathy.yaml:Patient-specific TNNT2 R173W iPSC-derived cardiomyocytes (Clinical Trials in a Dish)"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Dilated_Cardiomyopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dilated_Cardiomyopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy.html#dataset-geo-gse146621"]},{"id":"dataset:geo:gse146640","accession":"geo:GSE146640","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE146640","title":"Differences in transcription in Angelman syndrome and control person iPSC-derived neurons","alternate_titles":[],"description":"Human iPSC-neuron transcriptome dataset comparing Angelman syndrome and control lines to characterize disease-associated transcriptional changes.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":["Angelman syndrome iPSC-derived neurons","control iPSC-derived neurons"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE146640","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE146640","reference_title":"Differences in transcription in Angelman syndrome and control person iPSC-derived neurons","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"So we wanted to study differences in the transcriptome in neurons differentiated from iPSCs that were derived from patients with Angleman syndrome and normal controls.","explanation":"Supports direct disease-vs-control transcriptomic comparison in human neuron-like cells."}],"notes":[],"contexts":[{"id":"disorder:Angelman_Syndrome","name":"Angelman Syndrome","kind":"Disorder","source_path":"kb/disorders/Angelman_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Angelman_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Angelman_Syndrome.html#dataset-geo-gse146640"}],"context_names":["Angelman Syndrome"],"disease_names":["Angelman Syndrome"],"disease_name":"Angelman Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Angelman_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Angelman_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Angelman_Syndrome.html#dataset-geo-gse146640"]},{"id":"dataset:geo:gse147528","accession":"geo:GSE147528","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE147528","title":"Molecular characterization of selectively vulnerable neurons in Alzheimer's Disease","alternate_titles":[],"description":"Single-nucleus RNA-seq of caudal entorhinal cortex and superior frontal gyrus from post-mortem brains spanning the progression of tau neurofibrillary pathology. The dataset from which RORB was identified as a marker of selectively vulnerable excitatory neurons.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"Homo sapiens","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0002728","label":"entorhinal cortex","display_label":"entorhinal cortex","url":"http://purl.obolibrary.org/obo/UBERON_0002728"},{"id":"UBERON:0001870","label":"frontal cortex","display_label":"frontal cortex","url":"http://purl.obolibrary.org/obo/UBERON_0001870"}],"sample_type_labels":["entorhinal cortex","frontal cortex"],"sample_counts":[20],"sample_count":20,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:33432193"],"publication_contexts":[{"context_id":"disorder:Alzheimer_Disease","publication":"PMID:33432193"}],"publication":"PMID:33432193","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/33432193","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Underlies the Selective Vulnerability of RORB+ Entorhinal Excitatory Neurons node. Accession resolved against the GEO API with `just verify-datasets`. Re-deriving the RORB result from this dataset is not an independent test of it."],"contexts":[{"id":"disorder:Alzheimer_Disease","name":"Alzheimer Disease","kind":"Disorder","source_path":"kb/disorders/Alzheimer_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alzheimer_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Alzheimer_Disease.html#dataset-geo-gse147528"}],"context_names":["Alzheimer Disease"],"disease_names":["Alzheimer Disease"],"disease_name":"Alzheimer Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Alzheimer_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alzheimer_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Alzheimer_Disease.html#dataset-geo-gse147528"]},{"id":"dataset:geo:gse147944","accession":"geo:GSE147944","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE147944","title":"Genome-wide transcriptome analysis of the STAT6-regulated genes in advanced-stage cutaneous T-cell lymphoma [scRNA-seq]","alternate_titles":[],"description":"The signal transducer and activator of transcription 6 (STAT-6) is a critical up-stream mediator of IL-13 and IL-4 signaling and is constitutively activated in malignant lymphocytes from Sezary syndrome (SS) and mycosis fungoides (MF), the most common subtypes of cutaneous T-cell lymphomas. By combining genome-wide expression profiling with pharmacological STAT-6 inhibition, we have identified the genes regulated by STAT-6 in MF/SS tumors. We found that STAT-6 regulates several common pathways in MF/SS malignant lymphocytes that are associated with control of cell cycle progression and genomic stability as well as production of Th2 cytokines.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[7],"sample_count":7,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:32438399"],"publication_contexts":[{"context_id":"disorder:Sezary_Syndrome","publication":"PMID:32438399"}],"publication":"PMID:32438399","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32438399","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Sezary Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Sezary_Syndrome","name":"Sezary Syndrome","kind":"Disorder","source_path":"kb/disorders/Sezary_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sezary_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Sezary_Syndrome.html#dataset-geo-gse147944"}],"context_names":["Sezary Syndrome"],"disease_names":["Sezary Syndrome"],"disease_name":"Sezary Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Sezary_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sezary_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Sezary_Syndrome.html#dataset-geo-gse147944"]},{"id":"dataset:geo:gse147950","accession":"geo:GSE147950","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE147950","title":"A positive feedback circuit between mTORC1 signaling and cathelicidin promotes skin inflammation in rosacea [mouse]","alternate_titles":[],"description":"Mouse bulk RNA-seq from an LL-37-induced rosacea-like skin model, with and without rapamycin, used to define the mTORC1-cathelicidin positive feedback loop that amplifies cutaneous inflammation. Aligns with the cathelicidin/LL-37 arm of the pathograph.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":["rosacea-like mouse skin lesions","control mouse skin","rapamycin-treated skin"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:33734592"],"publication_contexts":[{"context_id":"disorder:Rosacea","publication":"PMID:33734592"}],"publication":"PMID:33734592","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/33734592","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE147950","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE147950","reference_title":"A positive feedback circuit between mTORC1 signaling and cathelicidin promotes skin inflammation in rosacea [mouse]","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"The goal of this study is to figure out the role of mTORC1 signaling in the pathogenesis of rosacea by comparing rosacea mouse model skin lesion transcriptome profiling (RNA-seq) to that of control mouse skin treated with or without rapamycin.","explanation":"GEO summary establishes this as a rosacea mouse-model transcriptome designed to interrogate mTORC1 signaling, a regulator upstream of the cathelicidin pathway modeled in this entry."}],"notes":[],"contexts":[{"id":"disorder:Rosacea","name":"Rosacea","kind":"Disorder","source_path":"kb/disorders/Rosacea.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rosacea.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Rosacea.html#dataset-geo-gse147950"}],"context_names":["Rosacea"],"disease_names":["Rosacea"],"disease_name":"Rosacea","same_context_model_ids":["model:kb/disorders/Rosacea.yaml:HaCaT keratinocytes under simulated rosacea conditions","model:kb/disorders/Rosacea.yaml:Paired lesional and non-lesional papulopustular rosacea skin explants","model:kb/disorders/Rosacea.yaml:SZ95 sebocyte and live Demodex mite co-culture"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Rosacea.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rosacea.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Rosacea.html#dataset-geo-gse147950"]},{"id":"dataset:geo:gse148020","accession":"geo:GSE148020","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE148020","title":"Genetic landscape and autoimmunity of monocytes in developing Vogt-Koyanagi-Harada disease","alternate_titles":[],"description":"Vogt-Koyanagi-Harada (VKH) disease is a systemic autoimmune disorder affecting multiple organs, including eyes, skin, and central nervous system. It is known that monocytes significantly contribute to the development of autoimmune disease. However, the subset heterogeneity with unique functions and signatures in human circulating monocytes and the identity of disease-specific monocytic populations remain largely unknown. Here, we employed an advanced single-cell RNA sequencing technology to systematically analyze 11259 human circulating monocytes and genetically defined their subpopulations.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Vogt-Koyanagi-Harada Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Vogt-Koyanagi-Harada_Disease","name":"Vogt-Koyanagi-Harada Disease","kind":"Disorder","source_path":"kb/disorders/Vogt-Koyanagi-Harada_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Vogt-Koyanagi-Harada_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Vogt-Koyanagi-Harada_Disease.html#dataset-geo-gse148020"}],"context_names":["Vogt-Koyanagi-Harada Disease"],"disease_names":["Vogt-Koyanagi-Harada Disease"],"disease_name":"Vogt-Koyanagi-Harada Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Vogt-Koyanagi-Harada_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Vogt-Koyanagi-Harada_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Vogt-Koyanagi-Harada_Disease.html#dataset-geo-gse148020"]},{"id":"dataset:geo:gse148021","accession":"geo:GSE148021","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE148021","title":"Brain areas involved with obsessive-compulsive disorder present different DNA methylation modulation","alternate_titles":[],"description":"Background: Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts and repetitive actions, that presents the involvement of the cortico-striatal areas. The contribution of environmental risk factors to OCD development suggests that epigenetic mechanisms may contribute to its pathophysiology. DNA methylation changes and gene expression were evaluated in post-mortem brain tissues of the cortical (anterior cingulate gyrus and orbitofrontal cortex) and ventral striatum (nucleus accumbens, caudate nucleus and putamen) areas from eight OCD patients and eight matched controls.","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[67],"sample_count":67,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:34717534"],"publication_contexts":[{"context_id":"disorder:Obsessive-Compulsive_Disorder","publication":"PMID:34717534"}],"publication":"PMID:34717534","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34717534","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Obsessive-Compulsive Disorder (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Obsessive-Compulsive_Disorder","name":"Obsessive-Compulsive Disorder","kind":"Disorder","source_path":"kb/disorders/Obsessive-Compulsive_Disorder.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Obsessive-Compulsive_Disorder.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Obsessive-Compulsive_Disorder.html#dataset-geo-gse148021"}],"context_names":["Obsessive-Compulsive Disorder"],"disease_names":["Obsessive-Compulsive Disorder"],"disease_name":"Obsessive-Compulsive Disorder","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Obsessive-Compulsive_Disorder.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Obsessive-Compulsive_Disorder.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Obsessive-Compulsive_Disorder.html#dataset-geo-gse148021"]},{"id":"dataset:geo:gse148247","accession":"geo:GSE148247","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE148247","title":"Tracheoesophageal fistula characterisation","alternate_titles":[],"description":"Esophageal atresia and tracheoesophageal fistula (EA/TEF) are relatively frequently occurring foregut malformations with a largely unknown etiology. EA/TEF is thought to have a strong genetic component and several genes have been proven to be involved in syndromic EA/TEF. However, it is not clear which biological processes or gene networks are disturbed. To gain more insight in the origin of the TEF, we aimed to examine and describe TEF composition using a combination of whole-genome transcription profiling and (immuno-) histochemical stainings. We hypothesized that such characterization of human TEFs provides insight in the molecular and mechanistic etiology of EA/TEF.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[31],"sample_count":31,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:33201890"],"publication_contexts":[{"context_id":"disorder:Esophageal_Atresia","publication":"PMID:33201890"}],"publication":"PMID:33201890","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/33201890","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Esophageal Atresia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Esophageal_Atresia","name":"Esophageal Atresia","kind":"Disorder","source_path":"kb/disorders/Esophageal_Atresia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Esophageal_Atresia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Esophageal_Atresia.html#dataset-geo-gse148247"}],"context_names":["Esophageal Atresia"],"disease_names":["Esophageal Atresia"],"disease_name":"Esophageal Atresia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Esophageal_Atresia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Esophageal_Atresia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Esophageal_Atresia.html#dataset-geo-gse148247"]},{"id":"dataset:geo:gse148381","accession":"geo:GSE148381","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE148381","title":"Genome wide expression from esophageal biopsies of subjects with EoE-like inflammatory diseases, eosinophilic esophagitis, gastroesophageal reflux disease and healthy controls","alternate_titles":[],"description":"Esophageal biopsy RNA was isolated from proximal esophageal biopsied RNA from patients with EoE-like inflammatory diseases (EoE-like esophagitis, lymphocytic esophagitis, non-specific esophagitis), patients with active EoE, patients with GERD, and unaffected healthy controls. EoE-like inflammatory disease patients were clinically active at the time when biopsies were taken. None of the patients (EoE-like inflammatory diseases, EoE, GERD and controls) were under anti-eosinophil treatment (including dietary restrictions). The quality of the RNA-seq data was assessed using fastqc v. 0.11.5 1) and RSeQC v. 2.6.4 2). The reads were mapped to the reference genome using HiSat2 v. 2.1.0 3).","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[51],"sample_count":51,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:35094416"],"publication_contexts":[{"context_id":"disorder:Gastroesophageal_Reflux_Disease","publication":"PMID:35094416"}],"publication":"PMID:35094416","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35094416","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Gastroesophageal Reflux Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Gastroesophageal_Reflux_Disease","name":"Gastroesophageal Reflux Disease","kind":"Disorder","source_path":"kb/disorders/Gastroesophageal_Reflux_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Gastroesophageal_Reflux_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Gastroesophageal_Reflux_Disease.html#dataset-geo-gse148381"}],"context_names":["Gastroesophageal Reflux Disease"],"disease_names":["Gastroesophageal Reflux Disease"],"disease_name":"Gastroesophageal Reflux Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Gastroesophageal_Reflux_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Gastroesophageal_Reflux_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Gastroesophageal_Reflux_Disease.html#dataset-geo-gse148381"]},{"id":"dataset:geo:gse14841","accession":"geo:GSE14841","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE14841","title":"Expression data from healthy volunteers and IBS patients","alternate_titles":[],"description":"Microarray profiling of jejunal mucosal biopsies from 5 IBS-D patients and 4 healthy volunteers as a pilot study to characterize gene expression patterns in diarrhea-predominant IBS.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0002115","label":"jejunum","display_label":"jejunal mucosa biopsy","url":"http://purl.obolibrary.org/obo/UBERON_0002115"}],"sample_type_labels":["jejunum"],"sample_counts":[9],"sample_count":9,"conditions":["IBS-D (diarrhea-predominant)","healthy controls"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Smaller pilot dataset often combined with GSE36701 for meta-analysis. Studies have identified 1257 differentially expressed genes between IBS-D and controls."],"contexts":[{"id":"disorder:Irritable_Bowel_Syndrome","name":"Irritable Bowel Syndrome","kind":"Disorder","source_path":"kb/disorders/Irritable_Bowel_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Irritable_Bowel_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Irritable_Bowel_Syndrome.html#dataset-geo-gse14841"}],"context_names":["Irritable Bowel Syndrome"],"disease_names":["Irritable Bowel Syndrome"],"disease_name":"Irritable Bowel Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Irritable_Bowel_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Irritable_Bowel_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Irritable_Bowel_Syndrome.html#dataset-geo-gse14841"]},{"id":"dataset:geo:gse148616","accession":"geo:GSE148616","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE148616","title":"Gene expression profile of human osteoclastoma bone tumor derived giant osteoclast cells","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[2],"sample_count":2,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Profiles the giant osteoclast compartment specifically, which is the reactive rather than neoplastic population - the one distinction this entry turns on. Small (n=2), so it is a resource pointer rather than a basis for quantitative claims. \"Osteoclastoma\" is the historical synonym for this disease, not a different entity."],"contexts":[{"id":"disorder:Bone_Giant_Cell_Tumor","name":"Bone Giant Cell Tumor","kind":"Disorder","source_path":"kb/disorders/Bone_Giant_Cell_Tumor.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bone_Giant_Cell_Tumor.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Bone_Giant_Cell_Tumor.html#dataset-geo-gse148616"}],"context_names":["Bone Giant Cell Tumor"],"disease_names":["Bone Giant Cell Tumor"],"disease_name":"Bone Giant Cell Tumor","same_context_model_ids":["model:kb/disorders/Bone_Giant_Cell_Tumor.yaml:CRISPR-Cas9 H3.3 G34W-edited GCTB tumor-derived cells","model:kb/disorders/Bone_Giant_Cell_Tumor.yaml:Monocyte osteoclastogenesis co-culture with GCTB stromal cells","model:kb/disorders/Bone_Giant_Cell_Tumor.yaml:Patient-derived GCTB stromal cell culture"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Bone_Giant_Cell_Tumor.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bone_Giant_Cell_Tumor.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Bone_Giant_Cell_Tumor.html#dataset-geo-gse148616"]},{"id":"dataset:geo:gse14882","accession":"geo:GSE14882","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE14882","title":"Expression data from human blood from MELAS patients and controls","alternate_titles":[],"description":"Affymetrix whole-blood transcriptomes from ten MELAS patients and controls, analysed with regulatory- and protein-interaction-network methods to look for master regulators and disease-modifying genes.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[16],"sample_count":16,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:21708074"],"publication_contexts":[{"context_id":"disorder:MELAS_Syndrome","publication":"PMID:21708074"}],"publication":"PMID:21708074","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/21708074","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:21708074","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/21708074","reference_title":"Whole blood genome-wide expression profiling and network analysis suggest MELAS master regulators.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"Correlation analyses of gene alterations and clinico-genetic data detected significant correlations between A3243G-induced nuclear gene expression changes and mutant mtDNA load as well as disease characteristics.","explanation":"Establishes that an accessible-tissue transcriptome tracks both mutant load and clinical features, the property a prognostic biomarker would need."}],"notes":["One of the few MELAS datasets from an accessible tissue, so it is the natural starting point for the prognostic-biomarker gap. It also reports correlations between expression change, mutant load, and clinical characteristics, which is the genotype-phenotype question in a blood sample. Ten patients and a 2011 array platform limit what can be asked of it; treat it as a hypothesis source, not a validation set."],"contexts":[{"id":"disorder:MELAS_Syndrome","name":"MELAS Syndrome","kind":"Disorder","source_path":"kb/disorders/MELAS_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MELAS_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/MELAS_Syndrome.html#dataset-geo-gse14882"}],"context_names":["MELAS Syndrome"],"disease_names":["MELAS Syndrome"],"disease_name":"MELAS Syndrome","same_context_model_ids":["model:kb/disorders/MELAS_Syndrome.yaml:m.3243A>G patient iPSC-derived neurons"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/MELAS_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MELAS_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/MELAS_Syndrome.html#dataset-geo-gse14882"]},{"id":"dataset:geo:gse148822","accession":"geo:GSE148822","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE148822","title":"Distinct amyloid-b and tau associated microglia profiles in Alzheimer's disease","alternate_titles":[],"description":"Human single-nucleus microglial profiling separating amyloid-associated from tau-associated microglial states.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"Homo sapiens","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0000956","label":"cerebral cortex","display_label":"cerebral cortex","url":"http://purl.obolibrary.org/obo/UBERON_0000956"}],"sample_type_labels":["cerebral cortex"],"sample_counts":[95],"sample_count":95,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:33609158"],"publication_contexts":[{"context_id":"disorder:Alzheimer_Disease","publication":"PMID:33609158"}],"publication":"PMID:33609158","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/33609158","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Directly relevant to the entry's repeated claim that glial responses are pathology-context-dependent rather than uniform, including the amyloid-versus-tau split curated on the Neuroinflammation node. Accession resolved against the GEO API with `just verify-datasets`."],"contexts":[{"id":"disorder:Alzheimer_Disease","name":"Alzheimer Disease","kind":"Disorder","source_path":"kb/disorders/Alzheimer_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alzheimer_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Alzheimer_Disease.html#dataset-geo-gse148822"}],"context_names":["Alzheimer Disease"],"disease_names":["Alzheimer Disease"],"disease_name":"Alzheimer Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Alzheimer_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alzheimer_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Alzheimer_Disease.html#dataset-geo-gse148822"]},{"id":"dataset:geo:gse149665","accession":"geo:GSE149665","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE149665","title":"Circulating microRNAs profile in patients with transthyretin variant amyloidosis","alternate_titles":[],"description":"Transthyretin variant amyloidosis (ATTRv) is a rare autosomal dominant disease characterized by the accumulation of amyloid in many organs, mostly causing a sensory-motor neuropathy, cardiomyopathy, and dysautonomia. The aim of the study was to report microRNAs (miRNAs) expression profile identified in the blood of ATTRv patients. 10 symptomatic ATTRv patients, 10 asymptomatic carriers of transthyretin variant (TTRv), 10 patients with Charcot-Marie-Tooth (CMT) disease, and 10 healthy controls were studied.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[40],"sample_count":40,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:32655365"],"publication_contexts":[{"context_id":"disorder:ATTR_Amyloidosis","publication":"PMID:32655365"}],"publication":"PMID:32655365","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32655365","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Hereditary Transthyretin Amyloidosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:ATTR_Amyloidosis","name":"Hereditary Transthyretin Amyloidosis","kind":"Disorder","source_path":"kb/disorders/ATTR_Amyloidosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/ATTR_Amyloidosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hereditary_Transthyretin_Amyloidosis.html#dataset-geo-gse149665"}],"context_names":["Hereditary Transthyretin Amyloidosis"],"disease_names":["Hereditary Transthyretin Amyloidosis"],"disease_name":"Hereditary Transthyretin Amyloidosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/ATTR_Amyloidosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/ATTR_Amyloidosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hereditary_Transthyretin_Amyloidosis.html#dataset-geo-gse149665"]},{"id":"dataset:geo:gse149688","accession":"geo:GSE149688","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE149688","title":"The KMT2D Kabuki syndrome histone methylase controls neural crest cell differentiation and facial morphology","alternate_titles":[],"description":"RNA-seq from E14.25 wild-type and Kmt2d neural crest cell knockout mouse palatal shelves, supporting analysis of KMT2D-dependent craniofacial developmental gene expression.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":["E14.25 wild-type palatal shelves","E14.25 Kmt2d neural crest cell knockout palatal shelves"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:32541010"],"publication_contexts":[{"context_id":"disorder:Kabuki_Syndrome","publication":"PMID:32541010"}],"publication":"PMID:32541010","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32541010","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:32541010","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/32541010","reference_title":"The KMT2D Kabuki syndrome histone methylase controls neural crest cell differentiation and facial morphology.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"We mutated KMT2D in neural crest cells (NCCs) to study cellular and molecular functions in craniofacial development with respect to UTX.","explanation":"Supports the mouse neural crest experimental context for this GEO RNA-seq dataset; the GEO accession identifies the deposited series."}],"notes":["GEO series linked to the KMT2D neural crest and palatal shelf model used to study craniofacial features of Kabuki syndrome."],"contexts":[{"id":"disorder:Kabuki_Syndrome","name":"Kabuki Syndrome","kind":"Disorder","source_path":"kb/disorders/Kabuki_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Kabuki_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Kabuki_Syndrome.html#dataset-geo-gse149688"}],"context_names":["Kabuki Syndrome"],"disease_names":["Kabuki Syndrome"],"disease_name":"Kabuki Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Kabuki_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Kabuki_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Kabuki_Syndrome.html#dataset-geo-gse149688"]},{"id":"dataset:geo:gse149871","accession":"geo:GSE149871","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE149871","title":"Epigenetic profiling of neuronal and non-neuronal signal in major depressive disorder","alternate_titles":[],"description":"Characterization of cell type specific (NeuN+/NeuN-) open chromatin by ATAC-seq assay in orbitofrontal cortext of postmortem tissue samples from 19 MMD cases and 18 controls.","alternate_descriptions":[],"data_types":["ATAC_SEQ"],"data_type_labels":["Assay for transposase-accessible chromatin sequencing"],"data_type_label":"Assay for transposase-accessible chromatin sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[70],"sample_count":70,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40516534"],"publication_contexts":[{"context_id":"disorder:Major_Depressive_Disorder","publication":"PMID:40516534"}],"publication":"PMID:40516534","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40516534","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Major Depressive Disorder (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Major_Depressive_Disorder","name":"Major Depressive Disorder","kind":"Disorder","source_path":"kb/disorders/Major_Depressive_Disorder.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Major_Depressive_Disorder.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Major_Depressive_Disorder.html#dataset-geo-gse149871"}],"context_names":["Major Depressive Disorder"],"disease_names":["Major Depressive Disorder"],"disease_name":"Major Depressive Disorder","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Major_Depressive_Disorder.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Major_Depressive_Disorder.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Major_Depressive_Disorder.html#dataset-geo-gse149871"]},{"id":"dataset:geo:gse150266","accession":"geo:GSE150266","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE150266","title":"Use of mice defective in interferon signaling to distinguish between primary and secondary pathological pathways in a mouse model of neuronal forms of Gaucher disease","alternate_titles":[],"description":"The type 1 interferon (IFN) response is part of the innate immune response and best known for its role in viral and bacterial infection. However, this pathway is also induced in sterile inflammation such as occurs in a number of neurodegenerative diseases, including neuronopathic Gaucher disease (nGD), a lysosomal storage disorder (LSD) caused by mutations in Gba1. Mice were injected with conduritol B-epoxide, an irreversible inhibitor of acid-beta glucosidase, the enzyme defective in nGD. Quadrat deficient MyTrMaSt mice, where four adaptors of pathogen recognition receptors (PRRs) are deficient, were used to determine the role of the IFN pathway in nGD pathology.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[14],"sample_count":14,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:32892753"],"publication_contexts":[{"context_id":"disorder:Gaucher_Disease","publication":"PMID:32892753"}],"publication":"PMID:32892753","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32892753","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Gaucher Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Gaucher_Disease","name":"Gaucher Disease","kind":"Disorder","source_path":"kb/disorders/Gaucher_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Gaucher_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Gaucher_Disease.html#dataset-geo-gse150266"}],"context_names":["Gaucher Disease"],"disease_names":["Gaucher Disease"],"disease_name":"Gaucher Disease","same_context_model_ids":["model:kb/disorders/Gaucher_Disease.yaml:CBE-treated murine macrophage conditioned-medium model","model:kb/disorders/Gaucher_Disease.yaml:GD1 patient bone marrow stromal cells"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Gaucher_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Gaucher_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Gaucher_Disease.html#dataset-geo-gse150266"]},{"id":"dataset:geo:gse150394","accession":"geo:GSE150394","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE150394","title":"A1-Reactive Astrocytes and a loss of TREM2 are associated to an early state of pathology in a mouse model of Cerebral Amyloid Angiopathy","alternate_titles":[],"description":"In this study, we dissect in detail the glial and immune responses associated to early stages of CAA. To do so, RNAseq gene expression analysis were performed in a mouse model for Familial Danish Dementia (FDD), a neurodegenerative disease characterized by the accumulation of Danish amyloid (ADan) in the vasculature. Findings observed in this CAA mouse model were complemented with primary culture assays.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:32711525"],"publication_contexts":[{"context_id":"disorder:Cerebral_Amyloid_Angiopathy","publication":"PMID:32711525"}],"publication":"PMID:32711525","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32711525","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Cerebral Amyloid Angiopathy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Cerebral_Amyloid_Angiopathy","name":"Cerebral Amyloid Angiopathy","kind":"Disorder","source_path":"kb/disorders/Cerebral_Amyloid_Angiopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cerebral_Amyloid_Angiopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cerebral_Amyloid_Angiopathy.html#dataset-geo-gse150394"}],"context_names":["Cerebral Amyloid Angiopathy"],"disease_names":["Cerebral Amyloid Angiopathy"],"disease_name":"Cerebral Amyloid Angiopathy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cerebral_Amyloid_Angiopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cerebral_Amyloid_Angiopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cerebral_Amyloid_Angiopathy.html#dataset-geo-gse150394"]},{"id":"dataset:geo:gse150598","accession":"geo:GSE150598","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE150598","title":"ATP mediates neuropathic pain of neuromyelitis optica spectrum disorder via microglial activation","alternate_titles":[],"description":"Intractable neuropathic pain is recognized as a common symptom of neuromyelitis optica spectrum disorder (NMOSD). However, the underlying mechanism of NMOSD pain remains to be elucidated. Here, we established NMOSD pain model by injecting anti-AQP4 recombinant autoantibodies (AQP4-Ab) generated from NMOSD patient’s plasmablasts into rat spinal cords and confirmed the development of mechanical allodynia. AQP4-Ab mediated extracellular ATP release from astrocytes and pharmacological inhibition of ATP receptor reversed mechanical allodynia in NMOSD pain model. Furthermore, transcriptome analysis revealed microglia activation and IL-1β elevation in NMOSD spinal cord.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10116","label":"Rattus norvegicus","display_label":"rat","url":"http://purl.obolibrary.org/obo/NCBITaxon_10116"}],"organism_labels":["Rattus norvegicus"],"organism_label":"Rattus norvegicus","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:34419102"],"publication_contexts":[{"context_id":"disorder:Neuromyelitis_Optica","publication":"PMID:34419102"},{"context_id":"disorder:Neuromyelitis_Optica_Spectrum_Disorder","publication":"PMID:34419102"}],"publication":"PMID:34419102","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34419102","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Neuromyelitis Optica (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.","Identified by GEO DataSets index search for Neuromyelitis Optica Spectrum Disorder (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Neuromyelitis_Optica","name":"Neuromyelitis Optica","kind":"Disorder","source_path":"kb/disorders/Neuromyelitis_Optica.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Neuromyelitis_Optica.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Neuromyelitis_Optica.html#dataset-geo-gse150598"},{"id":"disorder:Neuromyelitis_Optica_Spectrum_Disorder","name":"Neuromyelitis Optica Spectrum Disorder","kind":"Disorder","source_path":"kb/disorders/Neuromyelitis_Optica_Spectrum_Disorder.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Neuromyelitis_Optica_Spectrum_Disorder.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Neuromyelitis_Optica_Spectrum_Disorder.html#dataset-geo-gse150598"}],"context_names":["Neuromyelitis Optica","Neuromyelitis Optica Spectrum Disorder"],"disease_names":["Neuromyelitis Optica","Neuromyelitis Optica Spectrum Disorder"],"disease_name":"Neuromyelitis Optica","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Neuromyelitis_Optica.yaml","kb/disorders/Neuromyelitis_Optica_Spectrum_Disorder.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Neuromyelitis_Optica.yaml","https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Neuromyelitis_Optica_Spectrum_Disorder.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Neuromyelitis_Optica.html#dataset-geo-gse150598","https://dismech.monarchinitiative.org/pages/disorders/Neuromyelitis_Optica_Spectrum_Disorder.html#dataset-geo-gse150598"]},{"id":"dataset:geo:gse150600","accession":"geo:GSE150600","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE150600","title":"Inhibition of histone H3K27 demethylases inactivates brachyury (TBXT) and promotes chordoma cell death (ChIP-seq)","alternate_titles":[],"description":"Expression of the transcription factor brachyury (TBXT) is normally restricted to the embryo and its silencing is epigenetically regulated. TBXT promotes mesenchymal transition in a subset of common carcinomas, and in chordoma, a rare cancer showing notochordal differentiation, TBXT acts as a putative oncogene: we hypothesised that TBXT expression could be controlled through epigenetic inhibition to promote chordoma cell death. Screening of five human chordoma cell lines revealed that pharmacological inhibition of the histone 3 lysine 27 demethylases KDM6A (UTX) and KDM6B (JMJD3) leads to cell death. This effect was phenocopied by the dual genetic inactivation of KDM6A/B using CRISPR/Cas9.","alternate_descriptions":[],"data_types":["CHIP_SEQ"],"data_type_labels":["Chromatin immunoprecipitation sequencing"],"data_type_label":"Chromatin immunoprecipitation sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[34],"sample_count":34,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:32855205"],"publication_contexts":[{"context_id":"disorder:Chordoma","publication":"PMID:32855205"}],"publication":"PMID:32855205","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32855205","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Chordoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Chordoma","name":"Chordoma","kind":"Disorder","source_path":"kb/disorders/Chordoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chordoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chordoma.html#dataset-geo-gse150600"}],"context_names":["Chordoma"],"disease_names":["Chordoma"],"disease_name":"Chordoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chordoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chordoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chordoma.html#dataset-geo-gse150600"]},{"id":"dataset:geo:gse150674","accession":"geo:GSE150674","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE150674","title":"Transcriptional analysis of cystic fibrosis airways at single-cell resolution reveals altered epithelial cell states and composition","alternate_titles":[],"description":"Single-cell sequencing dataset of human airway epithelium from normal and cystic fibrosis lungs, including donor airway samples used to define altered epithelial cell-state composition in CF.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0001005","label":"respiratory airway","display_label":"proximal airway epithelium","url":"http://purl.obolibrary.org/obo/UBERON_0001005"}],"sample_type_labels":["respiratory airway"],"sample_counts":[38],"sample_count":38,"conditions":["cystic fibrosis","healthy control"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:33958799"],"publication_contexts":[{"context_id":"disorder:Cystic_Fibrosis","publication":"PMID:33958799"}],"publication":"PMID:33958799","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/33958799","publication_status":"Publication recorded","findings":[{"statement":"CF proximal airways show shifted epithelial-state composition with increased transitioning ciliated/secretory programs","evidence":[{"reference":"PMID:33958799","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33958799","reference_title":"Transcriptional analysis of cystic fibrosis airways at single-cell resolution reveals altered epithelial cell states and composition.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"Disease-dependent differences observed include an overabundance of epithelial cells transitioning to specialized ciliated and secretory cell subsets coupled with an unexpected decrease in cycling basal cells.","explanation":"Single-cell airway profiling identifies disease-dependent epithelial state shifts in CF."}]}],"findings_text":["CF proximal airways show shifted epithelial-state composition with increased transitioning ciliated/secretory programs"],"evidence":[{"reference":"PMID:33958799","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33958799","reference_title":"Transcriptional analysis of cystic fibrosis airways at single-cell resolution reveals altered epithelial cell states and composition.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"Disease-dependent differences observed include an overabundance of epithelial cells transitioning to specialized ciliated and secretory cell subsets coupled with an unexpected decrease in cycling basal cells.","explanation":"Single-cell airway profiling identifies disease-dependent epithelial state shifts in CF."}],"notes":["Donor-cohort count from the linked Nat Med study (19 CF + 19 healthy proximal-airway donors); GEO may include additional technical records not counted as biological samples."],"contexts":[{"id":"disorder:Cystic_Fibrosis","name":"Cystic Fibrosis","kind":"Disorder","source_path":"kb/disorders/Cystic_Fibrosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cystic_Fibrosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cystic_Fibrosis.html#dataset-geo-gse150674"}],"context_names":["Cystic Fibrosis"],"disease_names":["Cystic Fibrosis"],"disease_name":"Cystic Fibrosis","same_context_model_ids":["model:kb/disorders/Cystic_Fibrosis.yaml:CF airway-on-chip microphysiological model","model:kb/disorders/Cystic_Fibrosis.yaml:NuLi/CuFi airway epithelial cell-line model","model:kb/disorders/Cystic_Fibrosis.yaml:Patient-derived airway organoid theratyping model"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Cystic_Fibrosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cystic_Fibrosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cystic_Fibrosis.html#dataset-geo-gse150674"]},{"id":"dataset:geo:gse150910","accession":"geo:GSE150910","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE150910","title":"RNA-Sequencing of Chronic hypersensitivity pneumonitis compared with Idiopathic Pulmonary Fibrosis and Control Lung","alternate_titles":[],"description":"Bulk RNA-seq of whole lung tissue from chronic hypersensitivity pneumonitis, idiopathic pulmonary fibrosis, and controls. The HP samples are not stratified by inciting antigen, so this is shared HP context rather than a BFL-specific cohort.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0002048","label":"lung","display_label":"lung tissue","url":"http://purl.obolibrary.org/obo/UBERON_0002048"}],"sample_type_labels":["lung"],"sample_counts":[],"sample_count":null,"conditions":["hypersensitivity pneumonitis","idiopathic pulmonary fibrosis","normal lung"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:32602730"],"publication_contexts":[{"context_id":"disorder:Bird_Fanciers_Lung","publication":"PMID:32602730"}],"publication":"PMID:32602730","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32602730","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:32602730","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/32602730","reference_title":"Chronic Hypersensitivity Pneumonitis, an Interstitial Lung Disease with Distinct Molecular Signatures.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"Transcriptome analysis of lung samples from CHP (n = 82), IPF (n = 103), and unaffected controls (n = 103) was conducted.","explanation":"The study reports bulk transcriptome profiling of lung samples from chronic HP, IPF, and controls, matching the dataset description."}],"notes":["GEO record includes HP, IPF, and control whole-lung RNA-seq samples; avian exposure status is not supplied at dataset level."],"contexts":[{"id":"disorder:Bird_Fanciers_Lung","name":"Bird Fancier's Lung","kind":"Disorder","source_path":"kb/disorders/Bird_Fanciers_Lung.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bird_Fanciers_Lung.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Bird_Fancier's_Lung.html#dataset-geo-gse150910"}],"context_names":["Bird Fancier's Lung"],"disease_names":["Bird Fancier's Lung"],"disease_name":"Bird Fancier's Lung","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Bird_Fanciers_Lung.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bird_Fanciers_Lung.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Bird_Fancier's_Lung.html#dataset-geo-gse150910"]},{"id":"dataset:geo:gse151141","accession":"geo:GSE151141","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE151141","title":"The major and minor spliceosome interact to regulate alternative splicing [PBMCs]","alternate_titles":[],"description":"Mutations in minor spliceosome components are linked to diseases such as Roifman syndrome, Lowry-Wood syndrome, and early-onset cerebellar ataxia (EOCA). Here we report that besides increased minor intron retention, Roifman syndrome and EOCA can also be characterized by elevated alternative splicing (AS) around minor introns. Consistent with the idea that the assembly/activity of the minor spliceosome informs AS in minor intron-containing genes (MIGs), inhibition of all minor spliceosome snRNAs led to upregulated AS.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[8],"sample_count":8,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Roifman-syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Roifman-syndrome","name":"Roifman-syndrome","kind":"Disorder","source_path":"kb/disorders/Roifman-syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Roifman-syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Roifman-syndrome.html#dataset-geo-gse151141"}],"context_names":["Roifman-syndrome"],"disease_names":["Roifman-syndrome"],"disease_name":"Roifman-syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Roifman-syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Roifman-syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Roifman-syndrome.html#dataset-geo-gse151141"]},{"id":"dataset:geo:gse151713","accession":"geo:GSE151713","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE151713","title":"Dissecting the Transcriptomic Landscape of Circulating Mononuclear Phagocytes in Langerhans Cell Histiocytosis at Single-cell Level","alternate_titles":[],"description":"Langerhans cell histiocytosis (LCH) is a rarely clonal disorder caused by aberrant activation of MAPK pathway, which predominantly affects the mononuclear myeloid lineages. Many efforts have been devoted to tracking precursor cells in circulating blood and bone marrow by detection of BRAFV600E alleles and to exploring the differentiation potential of LCH-related myeloid cells in vitro. However, their cellular and molecular alterations remain unclear.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[38],"sample_count":38,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:34132762"],"publication_contexts":[{"context_id":"disorder:Langerhans_Cell_Histiocytosis","publication":"PMID:34132762"}],"publication":"PMID:34132762","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34132762","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Langerhans Cell Histiocytosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Langerhans_Cell_Histiocytosis","name":"Langerhans Cell Histiocytosis","kind":"Disorder","source_path":"kb/disorders/Langerhans_Cell_Histiocytosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Langerhans_Cell_Histiocytosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Langerhans_Cell_Histiocytosis.html#dataset-geo-gse151713"}],"context_names":["Langerhans Cell Histiocytosis"],"disease_names":["Langerhans Cell Histiocytosis"],"disease_name":"Langerhans Cell Histiocytosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Langerhans_Cell_Histiocytosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Langerhans_Cell_Histiocytosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Langerhans_Cell_Histiocytosis.html#dataset-geo-gse151713"]},{"id":"dataset:geo:gse152001","accession":"geo:GSE152001","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE152001","title":"Pseudoautosomal region 1 overdosage affects the global transcriptome in iPSCs from patients with Klinefelter syndrome and high-grade X chromosome aneuploidies","alternate_titles":[],"description":"Klinefelter syndrome (KS) is the most prevalent aneuploidy in males and is characterized by one or more supernumerary X chromosomes. Here, using a paradigmatic cohort of KS-inducible pluripotent stem cells (iPSCs) carrying 49-XXXXY, 48-XXXY, and 47-XXY karyotypes, we identified genes within the pseudoautosomal region 1 (PAR1) region as the most susceptible to dosage-dependent transcriptional dysregulation and therefore potentially responsible for the progressively worsening phenotype in higher grade X aneuploidies.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[72],"sample_count":72,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:35186953"],"publication_contexts":[{"context_id":"disorder:Klinefelter_Syndrome","publication":"PMID:35186953"}],"publication":"PMID:35186953","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35186953","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Klinefelter Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Klinefelter_Syndrome","name":"Klinefelter Syndrome","kind":"Disorder","source_path":"kb/disorders/Klinefelter_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Klinefelter_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Klinefelter_Syndrome.html#dataset-geo-gse152001"}],"context_names":["Klinefelter Syndrome"],"disease_names":["Klinefelter Syndrome"],"disease_name":"Klinefelter Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Klinefelter_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Klinefelter_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Klinefelter_Syndrome.html#dataset-geo-gse152001"]},{"id":"dataset:geo:gse152004","accession":"geo:GSE152004","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE152004","title":"Transcriptomic profiles of the nasal epithelium from the Genes-environments & Admixture in Latino Americans (GALA) II study","alternate_titles":[],"description":"Large cohort study of nasal epithelial cells comparing asthmatic and control subjects.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0001826","label":"nasal cavity mucosa","display_label":"nasal cavity mucosa","url":"http://purl.obolibrary.org/obo/UBERON_0001826"}],"sample_type_labels":["nasal cavity mucosa"],"sample_counts":[393],"sample_count":393,"conditions":["asthma (n=257)","controls (n=136)"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":[],"contexts":[{"id":"disorder:Asthma","name":"Asthma","kind":"Disorder","source_path":"kb/disorders/Asthma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Asthma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Asthma.html#dataset-geo-gse152004"}],"context_names":["Asthma"],"disease_names":["Asthma"],"disease_name":"Asthma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Asthma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Asthma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Asthma.html#dataset-geo-gse152004"]},{"id":"dataset:geo:gse153007","accession":"geo:GSE153007","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE153007","title":"Genome-Wide Profiling of Lesional and Non-Lesional Skin from Atopic Dermatitis, Psoriasis, and Contact Dermatitis Skin","alternate_titles":[],"description":"Comparative human skin transcriptomic dataset spanning lesional and non-lesional samples from contact dermatitis alongside atopic dermatitis and psoriasis, enabling cross-disease comparison of inflammatory programs.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"Homo sapiens","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":["contact dermatitis skin","non-lesional skin","atopic dermatitis skin","psoriasis skin"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Dataset record: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE153007 Carries no evidence block: the GEO record has no summary (its summary field repeats the title) and no linked publication, so there is no abstract sentence to quote. The title, conditions and organism above are GEO's own values."],"contexts":[{"id":"disorder:Contact_Dermatitis","name":"Contact Dermatitis","kind":"Disorder","source_path":"kb/disorders/Contact_Dermatitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Contact_Dermatitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Contact_Dermatitis.html#dataset-geo-gse153007"}],"context_names":["Contact Dermatitis"],"disease_names":["Contact Dermatitis"],"disease_name":"Contact Dermatitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Contact_Dermatitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Contact_Dermatitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Contact_Dermatitis.html#dataset-geo-gse153007"]},{"id":"dataset:geo:gse153540","accession":"geo:GSE153540","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE153540","title":"Transcriptional profiling of mouse prefrontal cortex and nucleus accumbens under chronic jet lag","alternate_titles":[],"description":"Chronic jet lag (CJL) induced by shifting light-dark cycles repeatedly is a commonly used protocol to mimic the environmental light/dark changes encountered by shift workers. We conducted RNA sequencing using prefrontal cortex (PFC) and nucleus accumbens (NAc) tissues from these animals, which are brains regions strongly implicated in the pathology of various neurological and psychiatric conditions. Our results reveal the alterations of brain activities and systematic reprogramming of gene expression in brain tissues under CJL, building hypothesis for how CJL increases the susceptibility to neurological and psychiatric diseases.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[24],"sample_count":24,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:33087702"],"publication_contexts":[{"context_id":"disorder:Jet_Lag","publication":"PMID:33087702"}],"publication":"PMID:33087702","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/33087702","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Jet Lag (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Jet_Lag","name":"Jet Lag","kind":"Disorder","source_path":"kb/disorders/Jet_Lag.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Jet_Lag.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Jet_Lag.html#dataset-geo-gse153540"}],"context_names":["Jet Lag"],"disease_names":["Jet Lag"],"disease_name":"Jet Lag","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Jet_Lag.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Jet_Lag.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Jet_Lag.html#dataset-geo-gse153540"]},{"id":"dataset:geo:gse153957","accession":"geo:GSE153957","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE153957","title":"Expression profiles and potential functions of long non-coding RNAs and mRNAs in autoimmune pulmonary alveolar proteinosis patients","alternate_titles":[],"description":"Microarray profiling of peripheral blood from five aPAP patients and five healthy volunteers. The sample source is peripheral blood rather than lung tissue, so it interrogates the systemic/autoimmune arm of the disease rather than the alveolar lesion directly.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[10],"sample_count":10,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:33820876"],"publication_contexts":[{"context_id":"disorder:Autoimmune_Pulmonary_Alveolar_Proteinosis","publication":"PMID:33820876"}],"publication":"PMID:33820876","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/33820876","publication_status":"Publication recorded","findings":[{"statement":"Large-scale differential expression of both lncRNAs and mRNAs distinguishes aPAP peripheral blood from healthy controls.","evidence":[]},{"statement":"Twelve differentially expressed lncRNAs survived qRT-PCR validation as candidate contributors to pathogenesis.","evidence":[]}],"findings_text":["Large-scale differential expression of both lncRNAs and mRNAs distinguishes aPAP peripheral blood from healthy controls.","Twelve differentially expressed lncRNAs survived qRT-PCR validation as candidate contributors to pathogenesis."],"evidence":[{"reference":"PMID:33820876","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33820876","reference_title":"Expression profiles and potential functions of long noncoding RNAs and mRNAs in autoimmune pulmonary alveolar proteinosis patients.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"we performed microarray analyses to identify differentially expressed (DE) lncRNAs and mRNAs between peripheral blood samples from five APAP patients and five healthy volunteers","explanation":"Defines the dataset design, sample source and cohort size."}],"notes":["Exploratory and small (n=5 per group). The reported lncRNA and ceRNA networks are hypothesis-generating and are deliberately NOT curated as pathophysiology nodes; no mechanistic claim in this entry rests on them."],"contexts":[{"id":"disorder:Autoimmune_Pulmonary_Alveolar_Proteinosis","name":"Autoimmune Pulmonary Alveolar Proteinosis","kind":"Disorder","source_path":"kb/disorders/Autoimmune_Pulmonary_Alveolar_Proteinosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autoimmune_Pulmonary_Alveolar_Proteinosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autoimmune_Pulmonary_Alveolar_Proteinosis.html#dataset-geo-gse153957"}],"context_names":["Autoimmune Pulmonary Alveolar Proteinosis"],"disease_names":["Autoimmune Pulmonary Alveolar Proteinosis"],"disease_name":"Autoimmune Pulmonary Alveolar Proteinosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Autoimmune_Pulmonary_Alveolar_Proteinosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autoimmune_Pulmonary_Alveolar_Proteinosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Autoimmune_Pulmonary_Alveolar_Proteinosis.html#dataset-geo-gse153957"]},{"id":"dataset:geo:gse153978","accession":"geo:GSE153978","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE153978","title":"Multiexon deletion alleles of ATF6 linked to achromatopsia","alternate_titles":[],"description":"Achromatopsia (ACHM) is an autosomal recessive disease that results in severe visual loss. Symptoms of ACHM include impaired visual acuity, nystagmus, and photoaversion starting from infancy; furthermore, ACHM is associated with bilateral foveal hypoplasia and absent or severely reduced cone photoreceptor function on electroretinography. Here, we performed genetic sequencing in 3 patients from 2 families with ACHM, identifying and functionally characterizing 2 mutations in the activating transcription factor 6 (ATF6) gene. We identified a homozygous deletion covering exons 8–14 of the ATF6 gene from 2 siblings from the same family.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:32271167"],"publication_contexts":[{"context_id":"disorder:Achromatopsia","publication":"PMID:32271167"}],"publication":"PMID:32271167","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32271167","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Achromatopsia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Achromatopsia","name":"Achromatopsia","kind":"Disorder","source_path":"kb/disorders/Achromatopsia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Achromatopsia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Achromatopsia.html#dataset-geo-gse153978"}],"context_names":["Achromatopsia"],"disease_names":["Achromatopsia"],"disease_name":"Achromatopsia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Achromatopsia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Achromatopsia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Achromatopsia.html#dataset-geo-gse153978"]},{"id":"dataset:geo:gse153990","accession":"geo:GSE153990","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE153990","title":"An iPSC-derived midbrain dopaminergic neuronal model of aromatic amino acid decarboxylase (AADC) deficiency gives insight into neurodevelopmental disease features","alternate_titles":[],"description":"Aromatic L-amino acid decarboxylase (AADC) deficiency is a complex inherited neurological disorder of monoamine synthesis which results in dopamine and serotonin deficiency. Affected patients have severe cognitive and motor delay, recurrent oculogyric crises, a complex movement disorder and high risk of premature mortality. Standard pharmacological treatment provides limited clinical benefit. Promising gene therapy approaches are emerging, though may not be either suitable or easily accessible for all patients.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[9],"sample_count":9,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:33734312"],"publication_contexts":[{"context_id":"disorder:Aromatic_L_Amino_Acid_Decarboxylase_Deficiency","publication":"PMID:33734312"}],"publication":"PMID:33734312","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/33734312","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Aromatic L-amino acid decarboxylase deficiency (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Aromatic_L_Amino_Acid_Decarboxylase_Deficiency","name":"Aromatic L-amino acid decarboxylase deficiency","kind":"Disorder","source_path":"kb/disorders/Aromatic_L_Amino_Acid_Decarboxylase_Deficiency.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Aromatic_L_Amino_Acid_Decarboxylase_Deficiency.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Aromatic_L-amino_acid_decarboxylase_deficiency.html#dataset-geo-gse153990"}],"context_names":["Aromatic L-amino acid decarboxylase deficiency"],"disease_names":["Aromatic L-amino acid decarboxylase deficiency"],"disease_name":"Aromatic L-amino acid decarboxylase deficiency","same_context_model_ids":["model:kb/disorders/Aromatic_L_Amino_Acid_Decarboxylase_Deficiency.yaml:DDC-knockout SH-SY5Y cell model"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Aromatic_L_Amino_Acid_Decarboxylase_Deficiency.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Aromatic_L_Amino_Acid_Decarboxylase_Deficiency.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Aromatic_L-amino_acid_decarboxylase_deficiency.html#dataset-geo-gse153990"]},{"id":"dataset:geo:gse154197","accession":"geo:GSE154197","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE154197","title":"INTS13 Mutations Causing a Developmental Ciliopathy Disrupt Integrator Complex Assembly","alternate_titles":[],"description":"RNA-seq of human cells depleted of INTS13, generated in the study that identified biallelic INTS13 variants in two families with variable orofaciodigital syndrome type 2 and showed that INTS13 depletion disrupts ciliogenesis and dysregulates a broad collection of ciliary genes.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[9],"sample_count":9,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:20174","label":"INTS13","display_label":"INTS13","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/20174"}],"genes":["INTS13"],"platforms":[],"platform":null,"publications":["PMID:36229431"],"publication_contexts":[{"context_id":"disorder:Orofaciodigital_Syndrome","publication":"PMID:36229431"}],"publication":"PMID:36229431","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36229431","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:36229431","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/36229431","reference_title":"INTS13 variants causing a recessive developmental ciliopathy disrupt assembly of the Integrator complex.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Depletion of INTS13 disrupts ciliogenesis in human cultured cells and causes dysregulation of a broad collection of ciliary genes.","explanation":"States the transcriptional result this dataset reports. Evidence source is IN_VITRO because the profiling was performed in cultured human cells."}],"notes":["Accession, title, organism and sample count verified against the NCBI GEO E-utilities record on 2026-08-19. Relevance is DIRECT rather than gene-only: the linked publication reports the affected families as having orofaciodigital syndrome type 2, not merely a ciliary gene of interest."],"contexts":[{"id":"disorder:Orofaciodigital_Syndrome","name":"Orofaciodigital Syndrome","kind":"Disorder","source_path":"kb/disorders/Orofaciodigital_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Orofaciodigital_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Orofaciodigital_Syndrome.html#dataset-geo-gse154197"}],"context_names":["Orofaciodigital Syndrome"],"disease_names":["Orofaciodigital Syndrome"],"disease_name":"Orofaciodigital Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Orofaciodigital_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Orofaciodigital_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Orofaciodigital_Syndrome.html#dataset-geo-gse154197"]},{"id":"dataset:geo:gse154199","accession":"geo:GSE154199","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE154199","title":"RNA sequencing of fibroblasts from patients with pathogenic KAT5 variants","alternate_titles":[],"description":"Bulk RNA sequencing of primary dermal fibroblasts from individuals carrying pathogenic KAT5 variants versus controls, the transcriptomic dataset underlying the developmental-gene deregulation and PER1 upregulation reported in the defining paper.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[11],"sample_count":11,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:32822602"],"publication_contexts":[{"context_id":"disorder:Neurodevelopmental_Disorder_With_Dysmorphic_Facies_Sleep_Disturbance_And_Brain_Abnormalities","publication":"PMID:32822602"}],"publication":"PMID:32822602","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32822602","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Accession, title, organism and sample count verified against NCBI GEO via E-utilities on 2026-08-15; the GEO record links to PMID 32822602."],"contexts":[{"id":"disorder:Neurodevelopmental_Disorder_With_Dysmorphic_Facies_Sleep_Disturbance_And_Brain_Abnormalities","name":"Neurodevelopmental Disorder With Dysmorphic Facies, Sleep Disturbance, and Brain Abnormalities","kind":"Disorder","source_path":"kb/disorders/Neurodevelopmental_Disorder_With_Dysmorphic_Facies_Sleep_Disturbance_And_Brain_Abnormalities.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Neurodevelopmental_Disorder_With_Dysmorphic_Facies_Sleep_Disturbance_And_Brain_Abnormalities.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Neurodevelopmental_Disorder_With_Dysmorphic_Facies,_Sleep_Disturbance,_and_Brain_Abnormalities.html#dataset-geo-gse154199"}],"context_names":["Neurodevelopmental Disorder With Dysmorphic Facies, Sleep Disturbance, and Brain Abnormalities"],"disease_names":["Neurodevelopmental Disorder With Dysmorphic Facies, Sleep Disturbance, and Brain Abnormalities"],"disease_name":"Neurodevelopmental Disorder With Dysmorphic Facies, Sleep Disturbance, and Brain Abnormalities","same_context_model_ids":["model:kb/disorders/Neurodevelopmental_Disorder_With_Dysmorphic_Facies_Sleep_Disturbance_And_Brain_Abnormalities.yaml:Genome-edited K562 cells expressing patient-variant KAT5","model:kb/disorders/Neurodevelopmental_Disorder_With_Dysmorphic_Facies_Sleep_Disturbance_And_Brain_Abnormalities.yaml:Patient-derived dermal fibroblasts"],"candidate_model_ids":["model:kb/disorders/Neurodevelopmental_Disorder_With_Dysmorphic_Facies_Sleep_Disturbance_And_Brain_Abnormalities.yaml:Genome-edited K562 cells expressing patient-variant KAT5","model:kb/disorders/Neurodevelopmental_Disorder_With_Dysmorphic_Facies_Sleep_Disturbance_And_Brain_Abnormalities.yaml:Patient-derived dermal fibroblasts"],"association_basis":"Same publication as a NAM (candidate)","nam_disease_context":"Same publication as a NAM (candidate)","source_paths":["kb/disorders/Neurodevelopmental_Disorder_With_Dysmorphic_Facies_Sleep_Disturbance_And_Brain_Abnormalities.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Neurodevelopmental_Disorder_With_Dysmorphic_Facies_Sleep_Disturbance_And_Brain_Abnormalities.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Neurodevelopmental_Disorder_With_Dysmorphic_Facies,_Sleep_Disturbance,_and_Brain_Abnormalities.html#dataset-geo-gse154199"]},{"id":"dataset:geo:gse154683","accession":"geo:GSE154683","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE154683","title":"Epigenomic profiles of African American Transthyretin Val122Ile carriers reveals putatively dysregulated amyloid mechanisms","alternate_titles":[],"description":"The Val122Ile mutation in Transthyretin (TTR) gene causes a rare, difficult to diagnose hereditary form of cardiac amyloidosis. This mutation is most common in the United States and mainly present in people of African descent. The carriers have an increased risk of congestive heart failure, peripheral edema, and several other non-cardiac phenotypes such as carpal tunnel syndrome, and arthroplasty which are top reasons for ambulatory/outpatient surgeries in the country. We conducted first-ever epigenome-wide association study in Val122Ile carriers of African descent for heart disease (HD) and multiple outpatient surgeries (OS) - an early disease indicator.","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[96],"sample_count":96,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:33428857"],"publication_contexts":[{"context_id":"disorder:ATTR_Amyloidosis","publication":"PMID:33428857"}],"publication":"PMID:33428857","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/33428857","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Hereditary Transthyretin Amyloidosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:ATTR_Amyloidosis","name":"Hereditary Transthyretin Amyloidosis","kind":"Disorder","source_path":"kb/disorders/ATTR_Amyloidosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/ATTR_Amyloidosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hereditary_Transthyretin_Amyloidosis.html#dataset-geo-gse154683"}],"context_names":["Hereditary Transthyretin Amyloidosis"],"disease_names":["Hereditary Transthyretin Amyloidosis"],"disease_name":"Hereditary Transthyretin Amyloidosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/ATTR_Amyloidosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/ATTR_Amyloidosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hereditary_Transthyretin_Amyloidosis.html#dataset-geo-gse154683"]},{"id":"dataset:geo:gse154700","accession":"geo:GSE154700","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE154700","title":"BPTF is essential for murine neocortical development","alternate_titles":[],"description":"Bulk forebrain RNA sequencing comparing Bptf Emx1-Cre conditional knockout and control mice at E13.5 and birth. GEO contains four control and four knockout samples at each stage, totaling 16 samples.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"Mus musculus","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[16],"sample_count":16,"conditions":["E13.5 control and Bptf forebrain conditional knockout","P0 control and Bptf forebrain conditional knockout"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["Illumina HiSeq 4000 and Illumina NovaSeq 6000"],"platform":"Illumina HiSeq 4000 and Illumina NovaSeq 6000","publications":["PMID:35604347"],"publication_contexts":[{"context_id":"disorder:BPTF-Related_Neurodevelopmental_Disorder","publication":"PMID:35604347"}],"publication":"PMID:35604347","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35604347","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["GEO GSE154700 lists 16 samples and two platforms. The overall-design field mentions P0 only, but the sample list also contains eight E13.5 samples. Bulk expression at birth is affected by altered neuronal abundance and microglial accumulation; changes are not necessarily cell-intrinsic or direct BPTF targets. This complete-loss mouse dataset is not a human heterozygous disease transcriptome."],"contexts":[{"id":"disorder:BPTF-Related_Neurodevelopmental_Disorder","name":"BPTF-Related Neurodevelopmental Disorder","kind":"Disorder","source_path":"kb/disorders/BPTF-Related_Neurodevelopmental_Disorder.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/BPTF-Related_Neurodevelopmental_Disorder.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/BPTF-Related_Neurodevelopmental_Disorder.html#dataset-geo-gse154700"}],"context_names":["BPTF-Related Neurodevelopmental Disorder"],"disease_names":["BPTF-Related Neurodevelopmental Disorder"],"disease_name":"BPTF-Related Neurodevelopmental Disorder","same_context_model_ids":["model:kb/disorders/BPTF-Related_Neurodevelopmental_Disorder.yaml:Bptf-null mouse embryonic stem cells and rescued embryoid bodies","model:kb/disorders/BPTF-Related_Neurodevelopmental_Disorder.yaml:P19 Bptf-knockdown Smad-response reporter model"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/BPTF-Related_Neurodevelopmental_Disorder.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/BPTF-Related_Neurodevelopmental_Disorder.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/BPTF-Related_Neurodevelopmental_Disorder.html#dataset-geo-gse154700"]},{"id":"dataset:geo:gse154778","accession":"geo:GSE154778","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE154778","title":"Single-cell transcriptomics analysis of pancreatic primary tumor and metastatic biopsy tissues","alternate_titles":[],"description":"Single-cell RNA-seq of 10 pancreatic primary tumors and 6 metastatic biopsies. Captures tumor, stromal, and immune programs across primary and metastatic disease, making it useful for modeling dissemination and metastatic niche adaptation in PDAC.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0001264","label":"pancreas","display_label":"pancreas","url":"http://purl.obolibrary.org/obo/UBERON_0001264"}],"sample_type_labels":["pancreas"],"sample_counts":[16],"sample_count":16,"conditions":["primary pancreatic ductal adenocarcinoma","metastatic pancreatic ductal adenocarcinoma"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:32988401"],"publication_contexts":[{"context_id":"disorder:Pancreatic_Ductal_Adenocarcinoma","publication":"PMID:32988401"}],"publication":"PMID:32988401","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32988401","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["GEO reports 10 primary tumors and 6 metastatic lesion biopsies profiled on the 10x Genomics Chromium platform. High-value bridge dataset between primary-tumor ecology and metastatic evolution."],"contexts":[{"id":"disorder:Pancreatic_Ductal_Adenocarcinoma","name":"Pancreatic Ductal Adenocarcinoma","kind":"Disorder","source_path":"kb/disorders/Pancreatic_Ductal_Adenocarcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pancreatic_Ductal_Adenocarcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pancreatic_Ductal_Adenocarcinoma.html#dataset-geo-gse154778"}],"context_names":["Pancreatic Ductal Adenocarcinoma"],"disease_names":["Pancreatic Ductal Adenocarcinoma"],"disease_name":"Pancreatic Ductal Adenocarcinoma","same_context_model_ids":["model:kb/disorders/Pancreatic_Ductal_Adenocarcinoma.yaml:Human PDAC Cell and Organoid RAS-Response Models"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Pancreatic_Ductal_Adenocarcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pancreatic_Ductal_Adenocarcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Pancreatic_Ductal_Adenocarcinoma.html#dataset-geo-gse154778"]},{"id":"dataset:geo:gse154825","accession":"geo:GSE154825","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE154825","title":"Sonlicromanol improves neuronal network dysfunction and transcriptome changes linked to m.3243A>G heteroplasmy in iPSC-derived neurons","alternate_titles":[],"description":"Combined micro-electrode array recording and RNA-seq (MEA-seq) of excitatory neurons differentiated from MELAS patient iPSCs at low and high m.3243A>G heteroplasmy, co-cultured with astrocytes, with and without sonlicromanol.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[16],"sample_count":16,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:34329596"],"publication_contexts":[{"context_id":"disorder:MELAS_Syndrome","publication":"PMID:34329596"}],"publication":"PMID:34329596","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34329596","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:34329596","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/34329596","reference_title":"Sonlicromanol improves neuronal network dysfunction and transcriptome changes linked to m.3243A>G heteroplasmy in iPSC-derived neurons.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We combined micro-electrode array (MEA) measurements with RNA sequencing (MEA-seq) and found reduced expression of genes involved in mitochondrial respiration and presynaptic function, as well as non-cell autonomous processes in co-cultured astrocytes.","explanation":"Couples network electrophysiology to transcriptome in m.3243A>G neurons and implicates astrocytes, the two elements the neuron-astrocyte uncoupling hypothesis requires."}],"notes":["The neuronal arm of the same controversy, and the only public MELAS dataset that measures network-level electrical activity rather than inferring it. It reports reduced presynaptic gene expression and non-cell-autonomous changes in co-cultured astrocytes, which is directly relevant to the neuron-astrocyte uncoupling variant of the hyperexcitability model. It also provides the transcriptomic readout for a drug now in a phase III trial in this entry."],"contexts":[{"id":"disorder:MELAS_Syndrome","name":"MELAS Syndrome","kind":"Disorder","source_path":"kb/disorders/MELAS_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MELAS_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/MELAS_Syndrome.html#dataset-geo-gse154825"}],"context_names":["MELAS Syndrome"],"disease_names":["MELAS Syndrome"],"disease_name":"MELAS Syndrome","same_context_model_ids":["model:kb/disorders/MELAS_Syndrome.yaml:m.3243A>G patient iPSC-derived neurons"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/MELAS_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MELAS_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/MELAS_Syndrome.html#dataset-geo-gse154825"]},{"id":"dataset:geo:gse155114","accession":"geo:GSE155114","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE155114","title":"Altered oligodendroglia and astroglia in chronic traumatic encephalopathy","alternate_titles":[],"description":"Chronic traumatic encephalopathy (CTE) is a progressive tauopathy found in contact sport athletes, military veterans, and others exposed to repetitive head injury. Brain white matter atrophy and axonal loss have been reported in CTE but have yet to be well characterized on a molecular or cellular level. Here, we present RNA sequencing profiles of cell nuclei from postmortem dorsolateral frontal white matter from eight individuals with neuropathologically confirmed CTE and eight age- and sex-matched controls.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[8],"sample_count":8,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:34019156"],"publication_contexts":[{"context_id":"disorder:Chronic_Traumatic_Encephalopathy","publication":"PMID:34019156"}],"publication":"PMID:34019156","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34019156","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Chronic Traumatic Encephalopathy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Chronic_Traumatic_Encephalopathy","name":"Chronic Traumatic Encephalopathy","kind":"Disorder","source_path":"kb/disorders/Chronic_Traumatic_Encephalopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Traumatic_Encephalopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chronic_Traumatic_Encephalopathy.html#dataset-geo-gse155114"}],"context_names":["Chronic Traumatic Encephalopathy"],"disease_names":["Chronic Traumatic Encephalopathy"],"disease_name":"Chronic Traumatic Encephalopathy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chronic_Traumatic_Encephalopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Traumatic_Encephalopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chronic_Traumatic_Encephalopathy.html#dataset-geo-gse155114"]},{"id":"dataset:geo:gse155141","accession":"geo:GSE155141","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE155141","title":"Paired transcriptomic and proteomic analysis implicates IL-1β in the pathogenesis of papulopustular rosacea explants [RNA-seq]","alternate_titles":[],"description":"Human RNA-seq dataset from paired non-lesional and lesional papulopustular rosacea explants, linked to paired proteomic profiling and inflammatory pathway analysis.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[15],"sample_count":15,"conditions":["non-lesional papulopustular rosacea skin","lesional papulopustular rosacea skin","IL-1beta-treated non-lesional rosacea skin"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:32941918"],"publication_contexts":[{"context_id":"disorder:Rosacea","publication":"PMID:32941918"}],"publication":"PMID:32941918","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32941918","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE155141","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE155141","reference_title":"Paired transcriptomic and proteomic analysis implicates IL-1β in the pathogenesis of papulopustular rosacea explants [RNA-seq]","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Our study suggests that MAPK and TNF signaling pathways are the most significantly upregulated pathways in lesional papulopustular rosacea human skins, highlighting IL-1β as a potential central mediator.","explanation":"This dataset captures lesion-associated inflammatory pathway activity in papulopustular rosacea. Graded IN_VITRO because the profiled material is cultured ex vivo biopsy explants, which this repository classes as in vitro, matching the sibling in vitro keratinocyte dataset geo:GSE303282."}],"notes":[],"contexts":[{"id":"disorder:Rosacea","name":"Rosacea","kind":"Disorder","source_path":"kb/disorders/Rosacea.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rosacea.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Rosacea.html#dataset-geo-gse155141"}],"context_names":["Rosacea"],"disease_names":["Rosacea"],"disease_name":"Rosacea","same_context_model_ids":["model:kb/disorders/Rosacea.yaml:HaCaT keratinocytes under simulated rosacea conditions","model:kb/disorders/Rosacea.yaml:Paired lesional and non-lesional papulopustular rosacea skin explants","model:kb/disorders/Rosacea.yaml:SZ95 sebocyte and live Demodex mite co-culture"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Rosacea.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rosacea.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Rosacea.html#dataset-geo-gse155141"]},{"id":"dataset:geo:gse155637","accession":"geo:GSE155637","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE155637","title":"Deferoxamine mesylate improves splicing and GAA activity of the common c.-32-13T>G allele in late-onset Pompe disease patient fibroblasts","alternate_titles":[],"description":"RNA-seq of primary fibroblasts from late-onset Pompe disease patients carrying the c.-32-13T>G allele, treated with deferoxamine or vehicle, testing pharmacological correction of the leaky-splicing defect that defines LOPD.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:4065","label":"GAA","display_label":"GAA","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/4065"}],"genes":["GAA"],"platforms":[],"platform":null,"publications":["PMID:33426149"],"publication_contexts":[{"context_id":"disorder:Late-Onset_Pompe_Disease","publication":"PMID:33426149"}],"publication":"PMID:33426149","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/33426149","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Discovered via `just discover-datasets Late-Onset_Pompe_Disease` as a DIRECT match (the disease and the c.-32-13T>G allele are both named in the dataset title) and manually triaged as on-topic for the leaky-splicing node of this entry. Verified with `just verify-datasets`. Retrieved 2026-08-18."],"contexts":[{"id":"disorder:Late-Onset_Pompe_Disease","name":"Late-Onset Pompe Disease","kind":"Disorder","source_path":"kb/disorders/Late-Onset_Pompe_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Late-Onset_Pompe_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Late-Onset_Pompe_Disease.html#dataset-geo-gse155637"}],"context_names":["Late-Onset Pompe Disease"],"disease_names":["Late-Onset Pompe Disease"],"disease_name":"Late-Onset Pompe Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Late-Onset_Pompe_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Late-Onset_Pompe_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Late-Onset_Pompe_Disease.html#dataset-geo-gse155637"]},{"id":"dataset:geo:gse155698","accession":"geo:GSE155698","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE155698","title":"Multimodal Mapping of the Tumor and Peripheral Blood Immune Landscape in Human Pancreatic Cancer","alternate_titles":[],"description":"Single-cell immune-focused PDAC resource spanning tumor tissue, adjacent normal pancreas, and peripheral blood mononuclear cells from pancreatic cancer patients, plus healthy-donor PBMC controls. Especially useful for linking the local TME to the systemic macroenvironment.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0001264","label":"pancreas","display_label":"pancreas","url":"http://purl.obolibrary.org/obo/UBERON_0001264"},{"id":"UBERON:0000178","label":"blood","display_label":"blood","url":"http://purl.obolibrary.org/obo/UBERON_0000178"}],"sample_type_labels":["pancreas","blood"],"sample_counts":[41],"sample_count":41,"conditions":["pancreatic ductal adenocarcinoma tumor tissue","adjacent normal pancreas","pancreatic cancer patient PBMCs","healthy donor PBMCs"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:34296197"],"publication_contexts":[{"context_id":"disorder:Pancreatic_Ductal_Adenocarcinoma","publication":"PMID:34296197"}],"publication":"PMID:34296197","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34296197","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Live GEO metadata lists 41 sample records, while the submitted design describes 16 tumor, 3 adjacent normal, 16 patient PBMC and 4 healthy PBMC samples (39 total). The discrepancy is preserved explicitly; reconcile the GSM-level manifest before cohort analysis and do not equate sample records with independent patients. Raw data are described as deposited in dbGaP phs002071.v1.p1; this review did not access controlled individual data."],"contexts":[{"id":"disorder:Pancreatic_Ductal_Adenocarcinoma","name":"Pancreatic Ductal Adenocarcinoma","kind":"Disorder","source_path":"kb/disorders/Pancreatic_Ductal_Adenocarcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pancreatic_Ductal_Adenocarcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pancreatic_Ductal_Adenocarcinoma.html#dataset-geo-gse155698"}],"context_names":["Pancreatic Ductal Adenocarcinoma"],"disease_names":["Pancreatic Ductal Adenocarcinoma"],"disease_name":"Pancreatic Ductal Adenocarcinoma","same_context_model_ids":["model:kb/disorders/Pancreatic_Ductal_Adenocarcinoma.yaml:Human PDAC Cell and Organoid RAS-Response Models"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Pancreatic_Ductal_Adenocarcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pancreatic_Ductal_Adenocarcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Pancreatic_Ductal_Adenocarcinoma.html#dataset-geo-gse155698"]},{"id":"dataset:geo:gse15571","accession":"geo:GSE15571","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE15571","title":"Gene Expression Changes Induced by Bacterial Superantigen, Staphylococcal Enterotoxin B","alternate_titles":[],"description":"Toxic shock syndrome (TSS) is an acute, serious systemic illness caused by bacterial superantigens (BSAg). We characterized the early molecular events underlying TSS using our HLA-DR3 transgenic mouse model and studied gene expression profiling using DNA microarrays.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[16],"sample_count":16,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:19336531"],"publication_contexts":[{"context_id":"disorder:Toxic_Shock_Syndrome","publication":"PMID:19336531"}],"publication":"PMID:19336531","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/19336531","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Toxic Shock Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-11. Relevance triaged manually: an HLA-DR3 transgenic mouse TSS model, the humanized-MHC approach that overcomes wild-type murine superantigen resistance."],"contexts":[{"id":"disorder:Toxic_Shock_Syndrome","name":"Toxic Shock Syndrome","kind":"Disorder","source_path":"kb/disorders/Toxic_Shock_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Toxic_Shock_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Toxic_Shock_Syndrome.html#dataset-geo-gse15571"}],"context_names":["Toxic Shock Syndrome"],"disease_names":["Toxic Shock Syndrome"],"disease_name":"Toxic Shock Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Toxic_Shock_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Toxic_Shock_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Toxic_Shock_Syndrome.html#dataset-geo-gse15571"]},{"id":"dataset:geo:gse156693","accession":"geo:GSE156693","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE156693","title":"Circulating miRNA sequencing in serum of patients with Cushing's syndrome and related controls","alternate_titles":[],"description":"Cushing’s syndrome (CS) is a rare disease with high morbidity and mortality. Diagnosis and subtyping are complex and challenging. Circulating microRNAs were described to be useful as minimally invasive diagnostic markers. Our aim was to determine and compare the circulating microRNA expression profiles of patients with CS and controls. We included three groups of patients of the German Cushing’s registry: A.) patients with florid adrenal dependent CS scheduled for adrenalectomy (CPA); B.) patients with florid pituitary dependent CS scheduled for surgery (CD); and C.) patients in whom CS had been ruled out (controls).","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[40],"sample_count":40,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:33692756"],"publication_contexts":[{"context_id":"disorder:Cushings_Syndrome","publication":"PMID:33692756"}],"publication":"PMID:33692756","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/33692756","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Cushing's Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Cushings_Syndrome","name":"Cushing's Syndrome","kind":"Disorder","source_path":"kb/disorders/Cushings_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cushings_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cushing's_Syndrome.html#dataset-geo-gse156693"}],"context_names":["Cushing's Syndrome"],"disease_names":["Cushing's Syndrome"],"disease_name":"Cushing's Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cushings_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cushings_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cushing's_Syndrome.html#dataset-geo-gse156693"]},{"id":"dataset:geo:gse156792","accession":"geo:GSE156792","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE156792","title":"Genome-epigenome interactions associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome","alternate_titles":[],"description":"Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex disease of unknown etiology. Multiple studies point to disruptions in immune functioning in ME/CFS patients as well as specific genetic polymorphisms and alterations of the DNA methylome in lymphocytes. However, potential interactions between DNA methylation and genetic background in relation to ME/CFS have not been examined. In this study we explored this association by characterizing the epigenetic (~480 thousand CpG loci) and genetic (~4.3 million SNPs) variation between cohorts of ME/CFS patients and healthy controls.","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[109],"sample_count":109,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:30516085"],"publication_contexts":[{"context_id":"disorder:Myalgic_Encephalomyelitis_Chronic_Fatigue_Syndrome","publication":"PMID:30516085"}],"publication":"PMID:30516085","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/30516085","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values. Accession reverified on 2026-09-04. Dataset records or repeated samples are not necessarily independent participants. Provider-report citation does not establish that OpenScientist downloaded or analyzed this dataset."],"contexts":[{"id":"disorder:Myalgic_Encephalomyelitis_Chronic_Fatigue_Syndrome","name":"Myalgic Encephalomyelitis/Chronic Fatigue Syndrome","kind":"Disorder","source_path":"kb/disorders/Myalgic_Encephalomyelitis_Chronic_Fatigue_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myalgic_Encephalomyelitis_Chronic_Fatigue_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Myalgic_Encephalomyelitis_Chronic_Fatigue_Syndrome.html#dataset-geo-gse156792"}],"context_names":["Myalgic Encephalomyelitis/Chronic Fatigue Syndrome"],"disease_names":["Myalgic Encephalomyelitis/Chronic Fatigue Syndrome"],"disease_name":"Myalgic Encephalomyelitis/Chronic Fatigue Syndrome","same_context_model_ids":["model:kb/disorders/Myalgic_Encephalomyelitis_Chronic_Fatigue_Syndrome.yaml:Erythrocyte Microfluidic Deformability Assay","model:kb/disorders/Myalgic_Encephalomyelitis_Chronic_Fatigue_Syndrome.yaml:Patient NK-Cell TRPM3 Assays","model:kb/disorders/Myalgic_Encephalomyelitis_Chronic_Fatigue_Syndrome.yaml:Patient Serum Vesicle-Microglia Assay","model:kb/disorders/Myalgic_Encephalomyelitis_Chronic_Fatigue_Syndrome.yaml:Patient T-Cell Metabolic Assays","model:kb/disorders/Myalgic_Encephalomyelitis_Chronic_Fatigue_Syndrome.yaml:Patient-Derived Skeletal Myotubes"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Myalgic_Encephalomyelitis_Chronic_Fatigue_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myalgic_Encephalomyelitis_Chronic_Fatigue_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Myalgic_Encephalomyelitis_Chronic_Fatigue_Syndrome.html#dataset-geo-gse156792"]},{"id":"dataset:geo:gse157240","accession":"geo:GSE157240","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE157240","title":"RNAseq analysis of blood from respiratory viruses-infected patients and healthy controls","alternate_titles":[],"description":"The objective of this study was to understand the shared and unique elements of the host transcriptional response to different viral pathogens. We identified 162 subjects in the US and Sri Lanka with infections due to influenza, enterovirus/rhinovirus, human metapneumovirus, dengue virus, cytomegalovirus, Epstein Barr Virus, or adenovirus. Our dataset allowed us to identify common pathways at the molecular level as well as virus-specific differences in the host immune response. Conserved elements of the host response to these viral infections high-lighted the importance of interferon pathway activation. However, the magnitude of the re-sponses varied between pathogens.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[187],"sample_count":187,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:34777354"],"publication_contexts":[{"context_id":"disorder:Adenovirus_Respiratory_Infection","publication":"PMID:34777354"},{"context_id":"disorder:Human_Metapneumovirus_Infection","publication":"PMID:34777354"}],"publication":"PMID:34777354","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34777354","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Adenovirus Respiratory Infection (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.","Identified by GEO DataSets index search for Human Metapneumovirus Infection (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Adenovirus_Respiratory_Infection","name":"Adenovirus Respiratory Infection","kind":"Disorder","source_path":"kb/disorders/Adenovirus_Respiratory_Infection.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Adenovirus_Respiratory_Infection.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Adenovirus_Respiratory_Infection.html#dataset-geo-gse157240"},{"id":"disorder:Human_Metapneumovirus_Infection","name":"Human Metapneumovirus Infection","kind":"Disorder","source_path":"kb/disorders/Human_Metapneumovirus_Infection.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Human_Metapneumovirus_Infection.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Human_Metapneumovirus_Infection.html#dataset-geo-gse157240"}],"context_names":["Adenovirus Respiratory Infection","Human Metapneumovirus Infection"],"disease_names":["Adenovirus Respiratory Infection","Human Metapneumovirus Infection"],"disease_name":"Adenovirus Respiratory Infection","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Adenovirus_Respiratory_Infection.yaml","kb/disorders/Human_Metapneumovirus_Infection.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Adenovirus_Respiratory_Infection.yaml","https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Human_Metapneumovirus_Infection.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Adenovirus_Respiratory_Infection.html#dataset-geo-gse157240","https://dismech.monarchinitiative.org/pages/disorders/Human_Metapneumovirus_Infection.html#dataset-geo-gse157240"]},{"id":"dataset:geo:gse157350","accession":"geo:GSE157350","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE157350","title":"Transcriptomics in whole-blood cells of Buruli ulcer patients identifies a signature of inflammation","alternate_titles":[],"description":"Mycolactone, a lipid-like toxin, is the major virulence factor of Mycobacterium ulcerans, the etiological agent of Buruli ulcer. Its involvement in lesions development has been widely described in early stages of the disease, through its cytotoxic and immunosuppressive activities, but less is known about later stages. Here, we revisit the role of mycolactone in disease outcome and provide the first demonstration of the pro-inflammatory potential of this toxin. We found that the mycolactone-containing mycobacterial extracellular vesicles produced by M. ulcerans induced the production of IL-1β, a potent pro-inflammatory cytokine, in a TLR2-dependent manner, targeting NLRP3/1 inflammasomes.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[100],"sample_count":100,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:33338061"],"publication_contexts":[{"context_id":"disorder:Buruli_Ulcer","publication":"PMID:33338061"}],"publication":"PMID:33338061","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/33338061","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Buruli ulcer (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Buruli_Ulcer","name":"Buruli ulcer","kind":"Disorder","source_path":"kb/disorders/Buruli_Ulcer.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Buruli_Ulcer.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Buruli_ulcer.html#dataset-geo-gse157350"}],"context_names":["Buruli ulcer"],"disease_names":["Buruli ulcer"],"disease_name":"Buruli ulcer","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Buruli_Ulcer.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Buruli_Ulcer.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Buruli_ulcer.html#dataset-geo-gse157350"]},{"id":"dataset:geo:gse157591","accession":"geo:GSE157591","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE157591","title":"MYC Promotes Bone Marrow Stem Cell Dysfunction in Fanconi Anemia","alternate_titles":[],"description":"Single-cell RNA sequencing of bone marrow CD34+ hematopoietic stem and progenitor cells from Fanconi anemia patients and healthy donors. Reveals aberrant MYC overexpression in FA HSPCs driving proliferation-apoptosis imbalance, with transcriptomic signatures distinct from normal hematopoiesis.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["10x Genomics Chromium"],"platform":"10x Genomics Chromium","publications":["PMID:32997960"],"publication_contexts":[{"context_id":"disorder:Fanconi_Anemia","publication":"PMID:32997960"}],"publication":"PMID:32997960","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32997960","publication_status":"Publication recorded","findings":[{"statement":"MYC is overexpressed in FA HSPCs compared to healthy donor HSPCs","evidence":[]},{"statement":"FA HSPCs show proliferation-apoptosis imbalance driven by MYC dysregulation","evidence":[]}],"findings_text":["MYC is overexpressed in FA HSPCs compared to healthy donor HSPCs","FA HSPCs show proliferation-apoptosis imbalance driven by MYC dysregulation"],"evidence":[{"reference":"PMID:32997960","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/32997960","reference_title":"MYC Promotes Bone Marrow Stem Cell Dysfunction in Fanconi Anemia.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"MYC overexpression impairs HSPC function in FA patients and contributes to exhaustion in FA bone marrow","explanation":"scRNA-seq dataset demonstrates MYC as a key driver of HSPC dysfunction in FA patients."}],"notes":[],"contexts":[{"id":"disorder:Fanconi_Anemia","name":"Fanconi_Anemia","kind":"Disorder","source_path":"kb/disorders/Fanconi_Anemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fanconi_Anemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Fanconi_Anemia.html#dataset-geo-gse157591"}],"context_names":["Fanconi_Anemia"],"disease_names":["Fanconi_Anemia"],"disease_name":"Fanconi_Anemia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Fanconi_Anemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fanconi_Anemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Fanconi_Anemia.html#dataset-geo-gse157591"]},{"id":"dataset:geo:gse157627","accession":"geo:GSE157627","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE157627","title":"The dynamic immune cell landscape in the lungs of Pneumocystis infected mice","alternate_titles":[],"description":"Pneumocystis pneumonia is an opportunistic pneumonia that has been increasing in non-HIV patients in recent years. To obtain a better understanding of the cellular and molecular mechanisms involved in disease pathogenesis, we profile the transcriptomes of mouse lungs with Pneumocystis pneumonia and from uninfected control subjects using single-cell RNA sequencing, yielding multiple populations of myeloid cells, T cells and B cells. We uncover a PCP-associated TREM2+ subpopulation of interstitial macrophages, which expands in PCP, differentiates from Ly6C+ monocytes. We also define the subsets of effector CD4+ T cells that expand after the infection of Pneumocystis.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:33959105"],"publication_contexts":[{"context_id":"disorder:Pneumocystis_Pneumonia","publication":"PMID:33959105"}],"publication":"PMID:33959105","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/33959105","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Pneumocystis Pneumonia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Pneumocystis_Pneumonia","name":"Pneumocystis Pneumonia","kind":"Disorder","source_path":"kb/disorders/Pneumocystis_Pneumonia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pneumocystis_Pneumonia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pneumocystis_Pneumonia.html#dataset-geo-gse157627"}],"context_names":["Pneumocystis Pneumonia"],"disease_names":["Pneumocystis Pneumonia"],"disease_name":"Pneumocystis Pneumonia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Pneumocystis_Pneumonia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pneumocystis_Pneumonia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Pneumocystis_Pneumonia.html#dataset-geo-gse157627"]},{"id":"dataset:geo:gse157628","accession":"geo:GSE157628","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE157628","title":"Transcriptome-wide Analysis of Intracranial Artery in Patients with Moyamoya Disease Showing Up-regulation of Immune Response, and Down-regulation of Oxidative Phosphorylation and DNA Repair","alternate_titles":[],"description":"Micro-samples of the middle cerebral artery (MCA) were collected from patients with MMD (n=11) and those with control (n=9). Using microarray techniques, transcriptome-wide analysis was performed. Comparison of the MCA gene expression between patients with MMD and control detected 62 and 26 genes whose expression was significantly (P<0.001, fold change>2) up- or down-regulated in the MCA of MMD.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[20],"sample_count":20,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:34469870"],"publication_contexts":[{"context_id":"disorder:Moyamoya_Disease","publication":"PMID:34469870"}],"publication":"PMID:34469870","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34469870","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Moyamoya Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Moyamoya_Disease","name":"Moyamoya Disease","kind":"Disorder","source_path":"kb/disorders/Moyamoya_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Moyamoya_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Moyamoya_Disease.html#dataset-geo-gse157628"}],"context_names":["Moyamoya Disease"],"disease_names":["Moyamoya Disease"],"disease_name":"Moyamoya Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Moyamoya_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Moyamoya_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Moyamoya_Disease.html#dataset-geo-gse157628"]},{"id":"dataset:geo:gse157676","accession":"geo:GSE157676","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE157676","title":"Human iNSC-derived brain organoid model of lysosomal storage disorder in Niemann-Pick disease type C","alternate_titles":[],"description":"Recent studies on developing three-dimensional (3D) brain organoids from stem cells have allowed the generation of in vitro models of neural disease and have enabled the screening of drugs because these organoids mimic the complexity of neural tissue. Niemann-Pick disease, type C (NPC) is a neurodegenerative lysosomal storage disorder caused by mutations in the NPC1 protein. The pathological features underlying NPC are characterized by the abnormal accumulation of cholesterol in acidic compartments, including late endosomes and lysosomes.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[9],"sample_count":9,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:33311479"],"publication_contexts":[{"context_id":"disorder:Niemann_Pick_Disease_Type_C","publication":"PMID:33311479"}],"publication":"PMID:33311479","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/33311479","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Niemann-Pick Disease Type C (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Niemann_Pick_Disease_Type_C","name":"Niemann-Pick Disease Type C","kind":"Disorder","source_path":"kb/disorders/Niemann_Pick_Disease_Type_C.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Niemann_Pick_Disease_Type_C.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Niemann-Pick_Disease_Type_C.html#dataset-geo-gse157676"}],"context_names":["Niemann-Pick Disease Type C"],"disease_names":["Niemann-Pick Disease Type C"],"disease_name":"Niemann-Pick Disease Type C","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Niemann_Pick_Disease_Type_C.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Niemann_Pick_Disease_Type_C.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Niemann-Pick_Disease_Type_C.html#dataset-geo-gse157676"]},{"id":"dataset:geo:gse157827","accession":"geo:GSE157827","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE157827","title":"Single-nucleus transcriptome analysis reveals dysregulation of angiogenic endothelial cells and neuroprotective glia in Alzheimer's disease","alternate_titles":[],"description":"Independent human cortical single-nucleus RNA-seq cohort with endothelial and glial coverage.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"Homo sapiens","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0000956","label":"cerebral cortex","display_label":"cerebral cortex","url":"http://purl.obolibrary.org/obo/UBERON_0000956"}],"sample_type_labels":["cerebral cortex"],"sample_counts":[21],"sample_count":21,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:32989152"],"publication_contexts":[{"context_id":"disorder:Alzheimer_Disease","publication":"PMID:32989152"}],"publication":"PMID:32989152","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32989152","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Curated as a replication cohort rather than for a specific node. Accession resolved against the GEO API with `just verify-datasets`."],"contexts":[{"id":"disorder:Alzheimer_Disease","name":"Alzheimer Disease","kind":"Disorder","source_path":"kb/disorders/Alzheimer_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alzheimer_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Alzheimer_Disease.html#dataset-geo-gse157827"}],"context_names":["Alzheimer Disease"],"disease_names":["Alzheimer Disease"],"disease_name":"Alzheimer Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Alzheimer_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alzheimer_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Alzheimer_Disease.html#dataset-geo-gse157827"]},{"id":"dataset:geo:gse157903","accession":"geo:GSE157903","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE157903","title":"brpf1 knockdown reduces inhibitory neurotransmission and regulates gene expression of GABAergic interneurons derived from MGE","alternate_titles":[],"description":"Bulk RNA sequencing of primary mouse MGE-derived GABAergic interneurons after AAV-shBrpf1 or scramble treatment.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"Mus musculus","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":["MGE interneuron culture, scramble control","MGE interneuron culture, Brpf1 shRNA"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["Illumina HiSeq 2500 (GPL17021)"],"platform":"Illumina HiSeq 2500 (GPL17021)","publications":["PMID:33744924"],"publication_contexts":[{"context_id":"disorder:BRPF1-Related_Intellectual_Disability","publication":"PMID:33744924"}],"publication":"PMID:33744924","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/33744924","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["GEO records three samples per condition. The paper reports three culture batches per condition. Transcript changes do not establish direct BRPF1 targets or mediation of electrophysiological changes."],"contexts":[{"id":"disorder:BRPF1-Related_Intellectual_Disability","name":"BRPF1-Related Intellectual Disability","kind":"Disorder","source_path":"kb/disorders/BRPF1-Related_Intellectual_Disability.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/BRPF1-Related_Intellectual_Disability.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/BRPF1-Related_Intellectual_Disability.html#dataset-geo-gse157903"}],"context_names":["BRPF1-Related Intellectual Disability"],"disease_names":["BRPF1-Related Intellectual Disability"],"disease_name":"BRPF1-Related Intellectual Disability","same_context_model_ids":["model:kb/disorders/BRPF1-Related_Intellectual_Disability.yaml:BRPF1 Pro370Ser patient-derived lymphoblastoid cells","model:kb/disorders/BRPF1-Related_Intellectual_Disability.yaml:Brpf1-knockdown mouse hippocampal neuron cultures","model:kb/disorders/BRPF1-Related_Intellectual_Disability.yaml:Brpf1-knockdown mouse MGE-derived interneuron cultures","model:kb/disorders/BRPF1-Related_Intellectual_Disability.yaml:Brpf1-null fetal-liver and neonatal marrow colony cultures","model:kb/disorders/BRPF1-Related_Intellectual_Disability.yaml:BRPF1-null human H1 embryonic stem cells with inducible rescue","model:kb/disorders/BRPF1-Related_Intellectual_Disability.yaml:Emx1-lineage Brpf1 conditional cortical neuron cultures","model:kb/disorders/BRPF1-Related_Intellectual_Disability.yaml:Inducible Brpf1-null mouse embryonic fibroblasts"],"candidate_model_ids":["model:kb/disorders/BRPF1-Related_Intellectual_Disability.yaml:Brpf1-knockdown mouse MGE-derived interneuron cultures"],"association_basis":"Same publication as a NAM (candidate)","nam_disease_context":"Same publication as a NAM (candidate)","source_paths":["kb/disorders/BRPF1-Related_Intellectual_Disability.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/BRPF1-Related_Intellectual_Disability.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/BRPF1-Related_Intellectual_Disability.html#dataset-geo-gse157903"]},{"id":"dataset:geo:gse157956","accession":"geo:GSE157956","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE157956","title":"RNA-seq strategy to study Mycobacterium ulcerans adaptation within our original mouse model of spontaneous healing.","alternate_titles":[],"description":"Mycobacterium ulcerans is the causal agent of Buruli ulcer, a chronic infectious disease and the third most common mycobacterial disease worldwide. Without early treatment, M. ulcerans provokes massive skin ulcers, caused by the mycolactone toxin, its main virulence factor. However, spontaneous healing may occur in Buruli ulcer patients several months or years after the disease onset. We have shown, in an original mouse model, that bacterial load remains high and viable in spontaneously healed tissues, suggesting that M. ulcerans switches to low levels of mycolactone production, adapting its strategy to survive in such a hostile environment.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[8],"sample_count":8,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:34107844"],"publication_contexts":[{"context_id":"disorder:Buruli_Ulcer","publication":"PMID:34107844"}],"publication":"PMID:34107844","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34107844","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Buruli ulcer (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Buruli_Ulcer","name":"Buruli ulcer","kind":"Disorder","source_path":"kb/disorders/Buruli_Ulcer.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Buruli_Ulcer.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Buruli_ulcer.html#dataset-geo-gse157956"}],"context_names":["Buruli ulcer"],"disease_names":["Buruli ulcer"],"disease_name":"Buruli ulcer","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Buruli_Ulcer.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Buruli_Ulcer.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Buruli_ulcer.html#dataset-geo-gse157956"]},{"id":"dataset:geo:gse158187","accession":"geo:GSE158187","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE158187","title":"Steady-state expression of Giardia lamblia transcripts","alternate_titles":[],"description":"Giardia trophozoite RNA-seq dataset used to quantify steady-state transcript expression and support refined Giardia gene models relevant to parasite biology in giardiasis.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:5741","label":"Giardia duodenalis","display_label":"Giardia duodenalis","url":"http://purl.obolibrary.org/obo/NCBITaxon_5741"}],"organism_labels":["Giardia duodenalis"],"organism_label":"Giardia duodenalis","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":["steady-state trophozoite transcript expression"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:35110372"],"publication_contexts":[{"context_id":"disorder:Giardiasis","publication":"PMID:35110372"}],"publication":"PMID:35110372","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35110372","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE158187","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE158187","reference_title":"Steady-state expression of Giardia lamblia transcripts","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"RNASequencing and RNA level measurements of G. lamblia transcripts during trophozite stage to compare expression between genes of interest","explanation":"GEO summary supports the transcriptomic scope and trophozoite stage."},{"reference":"PMID:35110372","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/35110372","reference_title":"Precise gene models using long-read sequencing reveal a unique poly(A) signal in Giardia lamblia.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Using long-read sequencing, we characterize the polyadenylation signal and related sequences surrounding Giardia lamblia cleavage sites for over 2600 genes.","explanation":"Abstract supports transcript-level molecular characterization aligned with this dataset."}],"notes":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE158187"],"contexts":[{"id":"disorder:Giardiasis","name":"Giardiasis","kind":"Disorder","source_path":"kb/disorders/Giardiasis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Giardiasis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Giardiasis.html#dataset-geo-gse158187"}],"context_names":["Giardiasis"],"disease_names":["Giardiasis"],"disease_name":"Giardiasis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Giardiasis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Giardiasis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Giardiasis.html#dataset-geo-gse158187"]},{"id":"dataset:geo:gse158994","accession":"geo:GSE158994","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE158994","title":"Expression data of the mouse heart of a nose-only HCN inhalation model and a subcutaneous KCN injection model","alternate_titles":[],"description":"Cardiac transcriptomes from two mouse cyanide-exposure models profiled by oligonucleotide microarray - nose-only hydrogen cyanide inhalation, chosen to be relevant to structure-fire smoke exposure, and subcutaneous potassium cyanide injection, the route conventionally used for countermeasure testing. The comparison is the point: the two routes give substantially different cardiac transcriptomes at every time point within 24 hours, which bears directly on how much of the countermeasure literature built on KCN injection transfers to inhalational poisoning.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"house mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[69],"sample_count":69,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:33914522"],"publication_contexts":[{"context_id":"disorder:Cyanide_Poisoning","publication":"PMID:33914522"}],"publication":"PMID:33914522","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/33914522","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE158994","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE158994","reference_title":null,"supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"Although the KCN injection model has been often used to evaluate medical countermeasures, this study demonstrated that cardiac transcriptomes are largely different from that of the HCN inhalation model at multiple time points within 24 hours after exposure.","explanation":"The repository summary states the route-dependence finding that makes this dataset relevant to the myocardial arm of the pathograph and to the interpretation of antidote studies performed with injected KCN."}],"notes":["Selected from `just discover-datasets` as the only DIRECT candidate; the remaining candidates were GENE_ONLY hits reached through TST and are about unrelated diseases."],"contexts":[{"id":"disorder:Cyanide_Poisoning","name":"Cyanide Poisoning","kind":"Disorder","source_path":"kb/disorders/Cyanide_Poisoning.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cyanide_Poisoning.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cyanide_Poisoning.html#dataset-geo-gse158994"}],"context_names":["Cyanide Poisoning"],"disease_names":["Cyanide Poisoning"],"disease_name":"Cyanide Poisoning","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cyanide_Poisoning.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cyanide_Poisoning.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cyanide_Poisoning.html#dataset-geo-gse158994"]},{"id":"dataset:geo:gse159039","accession":"geo:GSE159039","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE159039","title":"Bulk RNA-seq analysis of the effects of ECHS1 knockdown on cardiomyocyte transcriptome","alternate_titles":[],"description":"Bulk RNA-seq of ECHS1-knockdown versus control neonatal cardiomyocytes, linking ECHS1 loss to altered histone crotonylation — an example of acyl-CoA-driven protein and histone lysine-acylation effects.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:33683949"],"publication_contexts":[{"context_id":"disorder:ECHS1_Deficiency","publication":"PMID:33683949"}],"publication":"PMID:33683949","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/33683949","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Organism: rat (Rattus norvegicus), neonatal cardiomyocytes (siECHS1 vs control)."],"contexts":[{"id":"disorder:ECHS1_Deficiency","name":"ECHS1 Deficiency","kind":"Disorder","source_path":"kb/disorders/ECHS1_Deficiency.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/ECHS1_Deficiency.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/ECHS1_Deficiency.html#dataset-geo-gse159039"}],"context_names":["ECHS1 Deficiency"],"disease_names":["ECHS1 Deficiency"],"disease_name":"ECHS1 Deficiency","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/ECHS1_Deficiency.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/ECHS1_Deficiency.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/ECHS1_Deficiency.html#dataset-geo-gse159039"]},{"id":"dataset:geo:gse159062","accession":"geo:GSE159062","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE159062","title":"Transcriptomic profile of three-dimensional tissue-engineered human skeletal muscle model of Pompe disease and recombinant protein therapy","alternate_titles":[],"description":"RNA-seq of a three-dimensional tissue-engineered human skeletal muscle (\"myobundle\") model of infantile-onset Pompe disease with and without recombinant human GAA, giving a transcriptomic readout of the muscle response to the therapy this entry curates as its principal treatment. The model reproduces reduced GAA activity, elevated glycogen and lysosome abundance, and contractile sensitivity to metabolic stress.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[10],"sample_count":10,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:4065","label":"GAA","display_label":"GAA","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/4065"}],"genes":["GAA"],"platforms":[],"platform":null,"publications":["PMID:33953320"],"publication_contexts":[{"context_id":"disorder:Infantile-Onset_Pompe_Disease","publication":"PMID:33953320"}],"publication":"PMID:33953320","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/33953320","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:33953320","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33953320","reference_title":"Three-dimensional tissue-engineered human skeletal muscle model of Pompe disease.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"we report a three-dimensional primary human skeletal muscle (\"myobundle\") model of infantile-onset Pompe disease (IOPD) that recapitulates hallmark pathological features including reduced GAA enzyme activity, elevated glycogen content and lysosome abundance","explanation":"Establishes that the profiled system is a model of the infantile-onset form specifically, and which disease features it reproduces."},{"reference":"PMID:33953320","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33953320","reference_title":"Three-dimensional tissue-engineered human skeletal muscle model of Pompe disease.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"In vitro treatment of IOPD myobundles with rhGAA or adeno-associated virus (AAV)-mediated hGAA expression yields increased GAA activity and robust glycogen clearance, but no improvements in stress-induced functional deficits.","explanation":"Reports the dissociation this dataset captures - glycogen clears while a functional deficit persists - which is the in vitro counterpart of the incomplete skeletal-muscle response to enzyme replacement therapy curated in this entry."}],"notes":["Discovered via `just discover-datasets` as a DIRECT match and retained after manual relevance triage: the source publication describes the myobundles explicitly as a model of infantile-onset Pompe disease. Relevance caveat: it is an engineered in vitro system, so it bears on the GAA-deficiency mechanism and the enzyme-replacement response in human muscle rather than on the cardiac severity or infantile course observed in patients. The companion SuperSeries GSE159064 is deliberately not curated separately, since it contains this series. Verified with `just verify-datasets`. Retrieved 2026-09-01."],"contexts":[{"id":"disorder:Infantile-Onset_Pompe_Disease","name":"Infantile-Onset Pompe Disease","kind":"Disorder","source_path":"kb/disorders/Infantile-Onset_Pompe_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Infantile-Onset_Pompe_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Infantile-Onset_Pompe_Disease.html#dataset-geo-gse159062"}],"context_names":["Infantile-Onset Pompe Disease"],"disease_names":["Infantile-Onset Pompe Disease"],"disease_name":"Infantile-Onset Pompe Disease","same_context_model_ids":["model:kb/disorders/Infantile-Onset_Pompe_Disease.yaml:Patient-derived iPSC cardiomyocytes (PD-iCMs)"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Infantile-Onset_Pompe_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Infantile-Onset_Pompe_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Infantile-Onset_Pompe_Disease.html#dataset-geo-gse159062"]},{"id":"dataset:geo:gse159771","accession":"geo:GSE159771","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE159771","title":"Illumina NGS RNA-seq and RRBS Sequencing on Spaceflight Mouse Retina","alternate_titles":[],"description":"Integrated DNA methylome and transcriptome analysis of mouse retinas following 37-day spaceflight, revealing epigenetic clock deceleration and altered pathways involved in retinal disease.","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:34179686"],"publication_contexts":[{"context_id":"disorder:Spaceflight_Associated_Neuro-Ocular_Syndrome","publication":"PMID:34179686"}],"publication":"PMID:34179686","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34179686","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":[],"contexts":[{"id":"disorder:Spaceflight_Associated_Neuro-Ocular_Syndrome","name":"Spaceflight Associated Neuro-Ocular Syndrome","kind":"Disorder","source_path":"kb/disorders/Spaceflight_Associated_Neuro-Ocular_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Spaceflight_Associated_Neuro-Ocular_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Spaceflight_Associated_Neuro-Ocular_Syndrome.html#dataset-geo-gse159771"}],"context_names":["Spaceflight Associated Neuro-Ocular Syndrome"],"disease_names":["Spaceflight Associated Neuro-Ocular Syndrome"],"disease_name":"Spaceflight Associated Neuro-Ocular Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Spaceflight_Associated_Neuro-Ocular_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Spaceflight_Associated_Neuro-Ocular_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Spaceflight_Associated_Neuro-Ocular_Syndrome.html#dataset-geo-gse159771"]},{"id":"dataset:geo:gse160747","accession":"geo:GSE160747","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE160747","title":"Establishing a molecular phenotype for Angelman Syndrome stem cell-derived neurons","alternate_titles":[],"description":"Human stem-cell neuron RNA-seq dataset spanning isogenic control versus Angelman syndrome neuronal models and antisense-oligonucleotide intervention conditions relevant to UBE3A reinstatement biology.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[36],"sample_count":36,"conditions":["isogenic control and Angelman syndrome pluripotent stem cell-derived neurons","UBE3A ASO-treated H9 hESC-derived neurons","scramble ASO-treated H9 hESC-derived neurons"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE160747","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE160747","reference_title":"Establishing a molecular phenotype for Angelman Syndrome stem cell-derived neurons","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"mRNAseq on (1) isogenic control and Angelman Syndrome pluripotent stem cell-derived neurons or (2) antisense oligonucleotide-treated H9 hESC-derived neurons","explanation":"Supports mechanistically relevant transcriptomic profiling in human AS neuronal models and ASO-treated conditions."}],"notes":[],"contexts":[{"id":"disorder:Angelman_Syndrome","name":"Angelman Syndrome","kind":"Disorder","source_path":"kb/disorders/Angelman_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Angelman_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Angelman_Syndrome.html#dataset-geo-gse160747"}],"context_names":["Angelman Syndrome"],"disease_names":["Angelman Syndrome"],"disease_name":"Angelman Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Angelman_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Angelman_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Angelman_Syndrome.html#dataset-geo-gse160747"]},{"id":"dataset:geo:gse160936","accession":"geo:GSE160936","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE160936","title":"Diverse human astrocyte and microglial transcriptional responses to Alzheimer's pathology","alternate_titles":[],"description":"Human astrocyte and microglial transcriptional responses to Alzheimer pathology, profiled across donors.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"Homo sapiens","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0000956","label":"cerebral cortex","display_label":"cerebral cortex","url":"http://purl.obolibrary.org/obo/UBERON_0000956"}],"sample_type_labels":["cerebral cortex"],"sample_counts":[24],"sample_count":24,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:34767070"],"publication_contexts":[{"context_id":"disorder:Alzheimer_Disease","publication":"PMID:34767070"}],"publication":"PMID:34767070","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34767070","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Glia-focused, and so a natural place to characterize astrocyte and microglial responses to Alzheimer pathology. It is not a place to settle the cell-identity dispute curated on the Senescent Cell Accumulation node: it profiles glia only, so it carries no neuronal comparator and cannot adjudicate a glia-versus-neuron contrast, which needs both cell classes measured in the same assay. It can test whether a glial senescence signature is present; it cannot test whether glia rather than excitatory neurons are the senescent population. Accession resolved against the GEO API with `just verify-datasets`."],"contexts":[{"id":"disorder:Alzheimer_Disease","name":"Alzheimer Disease","kind":"Disorder","source_path":"kb/disorders/Alzheimer_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alzheimer_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Alzheimer_Disease.html#dataset-geo-gse160936"}],"context_names":["Alzheimer Disease"],"disease_names":["Alzheimer Disease"],"disease_name":"Alzheimer Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Alzheimer_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alzheimer_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Alzheimer_Disease.html#dataset-geo-gse160936"]},{"id":"dataset:geo:gse161041","accession":"geo:GSE161041","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE161041","title":"Epigenome wide Association and Stochastic Epigenetic Mutation analysis on 23 twin pairs heterogeneously affected by Congenital Hypothyroidism (CH).","alternate_titles":[],"description":"We performed a whole-genome DNA methylation analysis (Infinium HumanMethylation450 BeadChip) on peripheral whole blood of 23 twin pairs (10 monozygotic and 13 dizygotic) heterogeneously (4 concordant and 19 discordant) affected by Congenital Hypothyroidism (CH) at birth.","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[46],"sample_count":46,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:36071330"],"publication_contexts":[{"context_id":"disorder:Congenital_Hypothyroidism","publication":"PMID:36071330"}],"publication":"PMID:36071330","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36071330","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Congenital Hypothyroidism (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Congenital_Hypothyroidism","name":"Congenital Hypothyroidism","kind":"Disorder","source_path":"kb/disorders/Congenital_Hypothyroidism.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Congenital_Hypothyroidism.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Congenital_Hypothyroidism.html#dataset-geo-gse161041"}],"context_names":["Congenital Hypothyroidism"],"disease_names":["Congenital Hypothyroidism"],"disease_name":"Congenital Hypothyroidism","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Congenital_Hypothyroidism.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Congenital_Hypothyroidism.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Congenital_Hypothyroidism.html#dataset-geo-gse161041"]},{"id":"dataset:geo:gse161715","accession":"geo:GSE161715","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE161715","title":"Multifaceted Pathomolecular Mechanism of a VWF Large Deletion Involved in the Pathogenesis of Severe VWD","alternate_titles":[],"description":"An in-frame heterozygous large deletion of exons 4-34 of the von Willebrand factor (VWF) gene was identified in an index patient (IP) with type 3 von Willebrand disease (VWD), as the only mutation. The IP exhibited severe bleeding episodes despite prophylaxis treatment, with a short VWF half-life after infusion of VWF/FVIII concentrates. This study intends to elucidate the causal molecular mechanism of this large deletion. Transcript analysis confirmed transcription of normal VWF mRNA besides an aberrant deleted transcript. The amount of secreted VWF from blood outgrowth endothelial cells (BOECs) isolated from the IP was not significantly different from that of controls.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:34861678"],"publication_contexts":[{"context_id":"disorder:Hereditary_von_Willebrand_Disease","publication":"PMID:34861678"}],"publication":"PMID:34861678","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34861678","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Hereditary von Willebrand Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Hereditary_von_Willebrand_Disease","name":"Hereditary von Willebrand Disease","kind":"Disorder","source_path":"kb/disorders/Hereditary_von_Willebrand_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hereditary_von_Willebrand_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hereditary_von_Willebrand_Disease.html#dataset-geo-gse161715"}],"context_names":["Hereditary von Willebrand Disease"],"disease_names":["Hereditary von Willebrand Disease"],"disease_name":"Hereditary von Willebrand Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hereditary_von_Willebrand_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hereditary_von_Willebrand_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hereditary_von_Willebrand_Disease.html#dataset-geo-gse161715"]},{"id":"dataset:geo:gse162335","accession":"geo:GSE162335","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE162335","title":"Transcriptional Survey of Ileal-Anal Pouch Immune Cells from Ulcerative Colitis","alternate_titles":[],"description":"Restorative proctocolectomy with ileal pouch-anal anastomosis is a surgical procedure in patients with ulcerative colitis refractory to medical therapies. Pouchitis, the most common complication, is inflammation of the pouch of unknown etiology. To define how the intestinal immune system is distinctly organized in response to inflammation and to develop mechanistic hypotheses of pouchitis, we analyzed tissues from patients with and without pouchitis and from patients with ulcerative colitis using single-cell RNA sequencing.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[26],"sample_count":26,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:33359089"],"publication_contexts":[{"context_id":"disorder:Pouchitis","publication":"PMID:33359089"}],"publication":"PMID:33359089","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/33359089","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Pouchitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Pouchitis","name":"Pouchitis","kind":"Disorder","source_path":"kb/disorders/Pouchitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pouchitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pouchitis.html#dataset-geo-gse162335"}],"context_names":["Pouchitis"],"disease_names":["Pouchitis"],"disease_name":"Pouchitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Pouchitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pouchitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Pouchitis.html#dataset-geo-gse162335"]},{"id":"dataset:geo:gse163005","accession":"geo:GSE163005","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE163005","title":"Characterizing cerebrospinal fluid immunity in neurological manifestations of COVID-19","alternate_titles":[],"description":"Patients suffering from Coronavirus disease 2019 (COVID-19) can develop neurological sequelae, such as headache, neuroinflammatory or cerebrovascular disease. These conditions - here termed Neuro-COVID - are more frequent in patients with severe COVID-19. To understand the etiology of these neurological sequelae, we utilized single-cell sequencing and examined the immune cell profiles from the cerebrospinal fluid (CSF) of Neuro-COVID patients compared to patients with non-inflammatory and autoimmune neurological diseases or with viral encephalitis. The CSF of Neuro-COVID patients exhibited an expansion of dedifferentiated monocytes and of exhausted CD4+ T cells.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[38],"sample_count":38,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:33382973"],"publication_contexts":[{"context_id":"disorder:Viral_Encephalitis","publication":"PMID:33382973"}],"publication":"PMID:33382973","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/33382973","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Viral Encephalitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Viral_Encephalitis","name":"Viral Encephalitis","kind":"Disorder","source_path":"kb/disorders/Viral_Encephalitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Viral_Encephalitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Viral_Encephalitis.html#dataset-geo-gse163005"}],"context_names":["Viral Encephalitis"],"disease_names":["Viral Encephalitis"],"disease_name":"Viral Encephalitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Viral_Encephalitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Viral_Encephalitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Viral_Encephalitis.html#dataset-geo-gse163005"]},{"id":"dataset:geo:gse163196","accession":"geo:GSE163196","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE163196","title":"Bulk transcriptome sequencing (bulkRNA-seq) of peripheral blood leukocytes (PBLs) in the bacterial meningitis (BM) of children","alternate_titles":[],"description":"Purpose: Profiling the bulk transcriptomes of PBLs in sepsis-developed BM progression. Methods: The total RNA of PBLs from BM patients were extracted, and constructed into cDNA library. Raw data of mRNA profiles were sequenced by paired-end strategy. Gene-counts were generated through handling sequencing data with the combined workflow of UMI-tools, STAR, Subread package and Samtools. Results: Successfully acquirng multiple bulk-transcriptomic profiles of PBLs from BM patients in different sepsis conditions.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[25],"sample_count":25,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:36119025"],"publication_contexts":[{"context_id":"disorder:Bacterial_meningitis","publication":"PMID:36119025"}],"publication":"PMID:36119025","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36119025","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Bacterial meningitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Bacterial_meningitis","name":"Bacterial meningitis","kind":"Disorder","source_path":"kb/disorders/Bacterial_meningitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bacterial_meningitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Bacterial_meningitis.html#dataset-geo-gse163196"}],"context_names":["Bacterial meningitis"],"disease_names":["Bacterial meningitis"],"disease_name":"Bacterial meningitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Bacterial_meningitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bacterial_meningitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Bacterial_meningitis.html#dataset-geo-gse163196"]},{"id":"dataset:geo:gse16334","accession":"geo:GSE16334","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE16334","title":"Expression data from normal and Fanconi anemia low density bone marrow cells","alternate_titles":[],"description":"Fanconi anemia (FA) is a rare inherited disease complicated by aplastic anemia. There is evidence that hematopoietic stem cells have lost self replicative capacity and undergo apoptosis when exposed to inhibitory cytokines including interferon gamma and tumor necrosis factor-alpha. We used gene expression microarrays to identify transcriptomal differences between bone marrow cells from normal volunteers and from children and adults with Fanconi anemia","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[32],"sample_count":32,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:19850743"],"publication_contexts":[{"context_id":"disorder:Inherited_Aplastic_Anemia","publication":"PMID:19850743"}],"publication":"PMID:19850743","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/19850743","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Inherited Aplastic Anemia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Inherited_Aplastic_Anemia","name":"Inherited Aplastic Anemia","kind":"Disorder","source_path":"kb/disorders/Inherited_Aplastic_Anemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Inherited_Aplastic_Anemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Inherited_Aplastic_Anemia.html#dataset-geo-gse16334"}],"context_names":["Inherited Aplastic Anemia"],"disease_names":["Inherited Aplastic Anemia"],"disease_name":"Inherited Aplastic Anemia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Inherited_Aplastic_Anemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Inherited_Aplastic_Anemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Inherited_Aplastic_Anemia.html#dataset-geo-gse16334"]},{"id":"dataset:geo:gse164015","accession":"geo:GSE164015","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE164015","title":"Epithelial miR-141 regulates IL-13-induced airway mucus production [single-cell RNA-seq]","alternate_titles":[],"description":"Single-cell RNA sequencing of airway epithelial cells from asthmatic patients revealing cell-type specific transcriptional changes.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"CL:0002202","label":"epithelial cell of tracheobronchial tree","display_label":"epithelial cell of tracheobronchial tree","url":"http://purl.obolibrary.org/obo/CL_0002202"}],"sample_type_labels":["epithelial cell of tracheobronchial tree"],"sample_counts":[],"sample_count":null,"conditions":["asthmatic patients"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Reveals cell-type specific heterogeneity in asthmatic airways"],"contexts":[{"id":"disorder:Asthma","name":"Asthma","kind":"Disorder","source_path":"kb/disorders/Asthma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Asthma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Asthma.html#dataset-geo-gse164015"}],"context_names":["Asthma"],"disease_names":["Asthma"],"disease_name":"Asthma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Asthma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Asthma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Asthma.html#dataset-geo-gse164015"]},{"id":"dataset:geo:gse164208","accession":"geo:GSE164208","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE164208","title":"Expression profile of peripheral immune cells-derived coding and long non-coding RNAs in patients with proliferative vitreoretinopathy","alternate_titles":[],"description":"Peripheral immune response has been revealed to play a critical role in proliferative vitreoretinopathy (PVR). However, the reliable immune-related factors that are acting as prognostic indicators or therapeutic targets for PVR remain to explore further. Methods: In the current study, we applied whole-transcriptome sequencing to profile peripheral blood mononuclear cells (PBMCs) from PVR patients and also analyzed lncRNA-mRNA interactions in peripheral immune cells to explore the pathways that might mediate immunopathology and resultant retinal damage in PVR.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[24],"sample_count":24,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:33509158"],"publication_contexts":[{"context_id":"disorder:Proliferative_Vitreoretinopathy","publication":"PMID:33509158"}],"publication":"PMID:33509158","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/33509158","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Proliferative Vitreoretinopathy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Proliferative_Vitreoretinopathy","name":"Proliferative Vitreoretinopathy","kind":"Disorder","source_path":"kb/disorders/Proliferative_Vitreoretinopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Proliferative_Vitreoretinopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Proliferative_Vitreoretinopathy.html#dataset-geo-gse164208"}],"context_names":["Proliferative Vitreoretinopathy"],"disease_names":["Proliferative Vitreoretinopathy"],"disease_name":"Proliferative Vitreoretinopathy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Proliferative_Vitreoretinopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Proliferative_Vitreoretinopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Proliferative_Vitreoretinopathy.html#dataset-geo-gse164208"]},{"id":"dataset:geo:gse164490","accession":"geo:GSE164490","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE164490","title":"Pericardial fluid microRNAs in patients with arrhythmogenic right ventricular cardiomyopathy or ischemic heart disease","alternate_titles":[],"description":"Pericardial fluid is enriched by biologically active molecules of cardiovascular origin including microRNAs. Investigation of the disease-specific extracellular microRNAs could shed light on the molecular processes underlying disease development. Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart disease characterized by life-threatening arrhythmias and progressive heart failure development. The current data about the association between microRNAs and ARVC development are limited.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[9],"sample_count":9,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:33816578"],"publication_contexts":[{"context_id":"disorder:Arrhythmogenic_Right_Ventricular_Cardiomyopathy","publication":"PMID:33816578"}],"publication":"PMID:33816578","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/33816578","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for arrhythmogenic right ventricular cardiomyopathy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Arrhythmogenic_Right_Ventricular_Cardiomyopathy","name":"arrhythmogenic right ventricular cardiomyopathy","kind":"Disorder","source_path":"kb/disorders/Arrhythmogenic_Right_Ventricular_Cardiomyopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Arrhythmogenic_Right_Ventricular_Cardiomyopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/arrhythmogenic_right_ventricular_cardiomyopathy.html#dataset-geo-gse164490"}],"context_names":["arrhythmogenic right ventricular cardiomyopathy"],"disease_names":["arrhythmogenic right ventricular cardiomyopathy"],"disease_name":"arrhythmogenic right ventricular cardiomyopathy","same_context_model_ids":["model:kb/disorders/Arrhythmogenic_Right_Ventricular_Cardiomyopathy.yaml:Heterozygous plakoglobin-deficient (plakoglobin+/-) mouse"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Arrhythmogenic_Right_Ventricular_Cardiomyopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Arrhythmogenic_Right_Ventricular_Cardiomyopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/arrhythmogenic_right_ventricular_cardiomyopathy.html#dataset-geo-gse164490"]},{"id":"dataset:geo:gse164939","accession":"geo:GSE164939","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE164939","title":"Blastic plasmacytoid dendritic cell neoplasm: genomics mark epigenetic dysregulation as a primary therapeutic target","alternate_titles":[],"description":"RNA sequencing associated with the original epigenetic-regulation study: five discovery BPDCN samples, four extension BPDCN samples and four normal pDC controls. The dataset was subsequently reused in the neural-program study PMID:34572907.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:30381297"],"publication_contexts":[{"context_id":"disorder:Blastic_Plasmacytoid_Dendritic_Cell_Neoplasm","publication":"PMID:30381297"}],"publication":"PMID:30381297","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/30381297","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["The broader publication also includes whole-exome and histone-mark profiling; these modalities should not all be inferred from the BULK_RNA_SEQ label."],"contexts":[{"id":"disorder:Blastic_Plasmacytoid_Dendritic_Cell_Neoplasm","name":"Blastic Plasmacytoid Dendritic Cell Neoplasm","kind":"Disorder","source_path":"kb/disorders/Blastic_Plasmacytoid_Dendritic_Cell_Neoplasm.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Blastic_Plasmacytoid_Dendritic_Cell_Neoplasm.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Blastic_Plasmacytoid_Dendritic_Cell_Neoplasm.html#dataset-geo-gse164939"}],"context_names":["Blastic Plasmacytoid Dendritic Cell Neoplasm"],"disease_names":["Blastic Plasmacytoid Dendritic Cell Neoplasm"],"disease_name":"Blastic Plasmacytoid Dendritic Cell Neoplasm","same_context_model_ids":["model:kb/disorders/Blastic_Plasmacytoid_Dendritic_Cell_Neoplasm.yaml:CAL-1 and GEN2.2 BPDCN cell lines","model:kb/disorders/Blastic_Plasmacytoid_Dendritic_Cell_Neoplasm.yaml:Tet2-edited HOXB8 dendritic differentiation culture"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Blastic_Plasmacytoid_Dendritic_Cell_Neoplasm.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Blastic_Plasmacytoid_Dendritic_Cell_Neoplasm.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Blastic_Plasmacytoid_Dendritic_Cell_Neoplasm.html#dataset-geo-gse164939"]},{"id":"dataset:geo:gse165953","accession":"geo:GSE165953","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE165953","title":"Glutamate pathway dysfunction in MELAS syndrome is alleviated by ketogenic diet","alternate_titles":[],"description":"Multi-omic profiling of neuronal cybrids carrying graded m.3243A>G loads, reporting glutamate accumulation proportional to heteroplasmy, altered glutamate, GABA, and TCA-cycle gene clusters, confirmation in MELAS post-mortem brain, and reversal by ketone-body exposure.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[8],"sample_count":8,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:35884972"],"publication_contexts":[{"context_id":"disorder:MELAS_Syndrome","publication":"PMID:35884972"}],"publication":"PMID:35884972","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35884972","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:35884972","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/35884972","reference_title":"Glutamate-Induced Deregulation of Krebs Cycle in Mitochondrial Encephalopathy Lactic Acidosis Syndrome Stroke-Like Episodes (MELAS) Syndrome Is Alleviated by Ketone Body Exposure.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"These results were supported by post-mortem brain tissue analysis from a MELAS patient, confirming the glutamate dysregulation.","explanation":"Anchors the cell-model glutamate finding in human MELAS brain, which is what makes it usable for the cortical hyperexcitability question."},{"reference":"PMID:35884972","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/35884972","reference_title":"Glutamate-Induced Deregulation of Krebs Cycle in Mitochondrial Encephalopathy Lactic Acidosis Syndrome Stroke-Like Episodes (MELAS) Syndrome Is Alleviated by Ketone Body Exposure.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"a multi-omic integrated approach to MELAS cells revealed glutamate as a promising disease biomarker, while also indicating that a ketogenic diet should be tested in MELAS patients","explanation":"States both the biomarker candidacy and the therapeutic hypothesis that this dataset generated."}],"notes":["Sits across three of the gaps at once. Glutamate accumulation scaled to heteroplasmy is a candidate mechanism for the cortical hyperexcitability the non-ischemic model requires; the authors propose glutamate as a disease biomarker; and the ketone-body rescue is the preclinical rationale for the ketogenic-diet trial recorded in this entry. The post-mortem brain confirmation is what lifts it above a cell-line result."],"contexts":[{"id":"disorder:MELAS_Syndrome","name":"MELAS Syndrome","kind":"Disorder","source_path":"kb/disorders/MELAS_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MELAS_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/MELAS_Syndrome.html#dataset-geo-gse165953"}],"context_names":["MELAS Syndrome"],"disease_names":["MELAS Syndrome"],"disease_name":"MELAS Syndrome","same_context_model_ids":["model:kb/disorders/MELAS_Syndrome.yaml:m.3243A>G patient iPSC-derived neurons"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/MELAS_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MELAS_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/MELAS_Syndrome.html#dataset-geo-gse165953"]},{"id":"dataset:geo:gse166358","accession":"geo:GSE166358","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE166358","title":"Arid1a-Plagl1-Hh signaling is indispensable for differentiation-associated cell cycle arrest of tooth root progenitors [RNA-Seq]","alternate_titles":[],"description":"Bulk RNA-seq profiling in mouse tooth-root progenitor perturbation models highlighting Hh-linked root developmental arrest mechanisms.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[{"id":"UBERON:0003677","label":"tooth root","display_label":"tooth root progenitor tissue","url":"http://purl.obolibrary.org/obo/UBERON_0003677"}],"sample_type_labels":["tooth root"],"sample_counts":[6],"sample_count":6,"conditions":["Gli1-CreER;Arid1afl/fl conditional knockout","control"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["GPL19057"],"platform":"GPL19057","publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE166358","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE166358","reference_title":"Arid1a-Plagl1-Hh signaling is indispensable for differentiation-associated cell cycle arrest of tooth root progenitors [RNA-Seq]","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"We show that loss of Arid1a impairs the differentiation-associated cell cycle arrest of tooth root progenitors through Hh signaling regulation, leading to shortened roots.","explanation":"Supports root-development signaling mechanisms relevant to taurodontism pathobiology."}],"notes":[],"contexts":[{"id":"disorder:Taurodontism","name":"Taurodontism","kind":"Disorder","source_path":"kb/disorders/Taurodontism.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Taurodontism.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Taurodontism.html#dataset-geo-gse166358"}],"context_names":["Taurodontism"],"disease_names":["Taurodontism"],"disease_name":"Taurodontism","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association 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sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[59],"sample_count":59,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:34414385"],"publication_contexts":[{"context_id":"disorder:Multisystem_Inflammatory_Syndrome_in_Children_MIS-C","publication":"PMID:34414385"}],"publication":"PMID:34414385","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34414385","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Multisystem Inflammatory Syndrome in Children (MIS-C) (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Multisystem_Inflammatory_Syndrome_in_Children_MIS-C","name":"Multisystem Inflammatory Syndrome in Children (MIS-C)","kind":"Disorder","source_path":"kb/disorders/Multisystem_Inflammatory_Syndrome_in_Children_MIS-C.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Multisystem_Inflammatory_Syndrome_in_Children_MIS-C.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Multisystem_Inflammatory_Syndrome_in_Children_MIS-C.html#dataset-geo-gse167030"}],"context_names":["Multisystem Inflammatory Syndrome in Children (MIS-C)"],"disease_names":["Multisystem Inflammatory Syndrome in Children (MIS-C)"],"disease_name":"Multisystem Inflammatory Syndrome in Children (MIS-C)","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Multisystem_Inflammatory_Syndrome_in_Children_MIS-C.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Multisystem_Inflammatory_Syndrome_in_Children_MIS-C.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Multisystem_Inflammatory_Syndrome_in_Children_MIS-C.html#dataset-geo-gse167030"]},{"id":"dataset:geo:gse167197","accession":"geo:GSE167197","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE167197","title":"Peroxisome import stress induces eIF2α phosphorylation and impairs ribosome biogenesis","alternate_titles":[],"description":"Peroxisome biogenesis diseases (PBDs) are characterized by global defects in peroxisomal function and can result in severe brain, liver, kidney, and bone malfunctions. 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The cached summary does not establish a sample count for a processed-expression subset or raw-data availability, so neither is asserted here. It should not be treated as representative of every pediatric, testicular, mediastinal, CNS, or somatically derived YST."],"contexts":[{"id":"disorder:Yolk_Sac_Tumor","name":"Yolk Sac Tumor","kind":"Disorder","source_path":"kb/disorders/Yolk_Sac_Tumor.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Yolk_Sac_Tumor.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Yolk_Sac_Tumor.html#dataset-geo-gse169733"}],"context_names":["Yolk Sac Tumor"],"disease_names":["Yolk Sac Tumor"],"disease_name":"Yolk Sac Tumor","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Yolk_Sac_Tumor.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Yolk_Sac_Tumor.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Yolk_Sac_Tumor.html#dataset-geo-gse169733"]},{"id":"dataset:geo:gse169753","accession":"geo:GSE169753","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE169753","title":"miR-22 and miR-205 drive tumor aggressiveness of mucoepidermoid carcinomas of salivary glands [mRNA]","alternate_titles":[],"description":"We used mRNA expression arrays and integrated analysis to study mucoepidermoid carcinomas (MEC) to identify potential drivers involved with its pathogenesis. 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Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Mucoepidermoid_Carcinoma","name":"Mucoepidermoid Carcinoma","kind":"Disorder","source_path":"kb/disorders/Mucoepidermoid_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mucoepidermoid_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Mucoepidermoid_Carcinoma.html#dataset-geo-gse169753"}],"context_names":["Mucoepidermoid Carcinoma"],"disease_names":["Mucoepidermoid Carcinoma"],"disease_name":"Mucoepidermoid Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Mucoepidermoid_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mucoepidermoid_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Mucoepidermoid_Carcinoma.html#dataset-geo-gse169753"]},{"id":"dataset:geo:gse171458","accession":"geo:GSE171458","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE171458","title":"Single-cell profiling reveals transcriptional signatures, novel epithelial cells and cell-cell crosstalk in idiopathic membranous nephropathy patients","alternate_titles":[],"description":"Our understanding of the pathogenesis of idiopathic membranous nephropathy is limited by an incomplete molecular characterization of the cell types in the kidney and interaction between the cells. Besides, the reason for the heterogeneity of these patients as well as the variety of clinical outcomes remains elusive. Therefore, we applied scRNA-seq to kidney biopsies of patients with IMN to identify gene expression at the single-cell level, elucidate cells involved in the progression of IMN, and uncover intercellular interactions.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[8],"sample_count":8,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:34135910"],"publication_contexts":[{"context_id":"disorder:Membranous_Nephropathy","publication":"PMID:34135910"}],"publication":"PMID:34135910","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34135910","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Membranous nephropathy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Membranous_Nephropathy","name":"Membranous nephropathy","kind":"Disorder","source_path":"kb/disorders/Membranous_Nephropathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Membranous_Nephropathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Membranous_nephropathy.html#dataset-geo-gse171458"}],"context_names":["Membranous nephropathy"],"disease_names":["Membranous nephropathy"],"disease_name":"Membranous nephropathy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Membranous_Nephropathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Membranous_Nephropathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Membranous_nephropathy.html#dataset-geo-gse171458"]},{"id":"dataset:geo:gse171795","accession":"geo:GSE171795","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE171795","title":"Role of activated PI3K-delta signaling in humoral immunity","alternate_titles":[],"description":"We report the high-throughput profiling of murine naive B cells, germinal center (dark zone and light zone) B cells, and plasma cells transcriptome. By obtaining over 5 million bases of sequence, we generated genome-wide expression maps of cell subsets from WT mice and aPIK3CD mice. We find that activated PIK3CD signaling lead to significant alteration in gene expression of plasma cells.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[32],"sample_count":32,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:34586341"],"publication_contexts":[{"context_id":"disorder:Activated_PI3K-delta_Syndrome","publication":"PMID:34586341"}],"publication":"PMID:34586341","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34586341","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Activated PI3K-delta syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Activated_PI3K-delta_Syndrome","name":"Activated PI3K-delta syndrome","kind":"Disorder","source_path":"kb/disorders/Activated_PI3K-delta_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Activated_PI3K-delta_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Activated_PI3K-delta_syndrome.html#dataset-geo-gse171795"}],"context_names":["Activated PI3K-delta syndrome"],"disease_names":["Activated PI3K-delta syndrome"],"disease_name":"Activated PI3K-delta syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Activated_PI3K-delta_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Activated_PI3K-delta_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Activated_PI3K-delta_syndrome.html#dataset-geo-gse171795"]},{"id":"dataset:geo:gse171827","accession":"geo:GSE171827","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE171827","title":"Plasma circRNA-expression profiles in children with pulmonary hypertension secondary to congenital heart disease","alternate_titles":[],"description":"Microarray analysis of circular RNA expression in plasma from 8 children with pulmonary arterial hypertension secondary to congenital heart disease compared to 5 controls without PAH. Identifies differentially expressed circRNAs that may serve as biomarkers for PAH-CHD.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[13],"sample_count":13,"conditions":["pulmonary arterial hypertension secondary to congenital heart disease","controls without pulmonary hypertension"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["Arraystar Human CircRNA Microarray V2"],"platform":"Arraystar Human CircRNA Microarray V2","publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["No scimitar syndrome-specific transcriptomic datasets exist in GEO. This dataset is the closest match, profiling circRNA in pediatric PAH secondary to CHD with left-to-right shunts, directly relevant to the pulmonary hypertension phenotype that drives morbidity in scimitar syndrome."],"contexts":[{"id":"disorder:Scimitar_Syndrome","name":"Scimitar Syndrome","kind":"Disorder","source_path":"kb/disorders/Scimitar_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Scimitar_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Scimitar_Syndrome.html#dataset-geo-gse171827"}],"context_names":["Scimitar Syndrome"],"disease_names":["Scimitar Syndrome"],"disease_name":"Scimitar Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Scimitar_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Scimitar_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Scimitar_Syndrome.html#dataset-geo-gse171827"]},{"id":"dataset:geo:gse173079","accession":"geo:GSE173079","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE173079","title":"Rising from the dead: A novel mechanism involving pyroptosis and pathologic neovascularization in retinopathy of prematurity","alternate_titles":[],"description":"To elucidate the changes in retinal angiogenesis, we performed single-cell RNA sequencing on OIR model isolated retinal cells.We found the specific expression of AIP1 gene in endothelial cells, which is related to the formation and development of retinal blood vessels, and the expression of AIP1 gene may play a protective role in the progression of disease.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39527457"],"publication_contexts":[{"context_id":"disorder:Retinopathy_of_Prematurity","publication":"PMID:39527457"}],"publication":"PMID:39527457","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39527457","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Retinopathy of Prematurity (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Retinopathy_of_Prematurity","name":"Retinopathy of Prematurity","kind":"Disorder","source_path":"kb/disorders/Retinopathy_of_Prematurity.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Retinopathy_of_Prematurity.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Retinopathy_of_Prematurity.html#dataset-geo-gse173079"}],"context_names":["Retinopathy of Prematurity"],"disease_names":["Retinopathy of Prematurity"],"disease_name":"Retinopathy of Prematurity","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Retinopathy_of_Prematurity.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Retinopathy_of_Prematurity.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Retinopathy_of_Prematurity.html#dataset-geo-gse173079"]},{"id":"dataset:geo:gse173129","accession":"geo:GSE173129","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE173129","title":"Differential gene expression and pathway analysis by RNA sequencing in human OPTN(E50K) astrocytes","alternate_titles":[],"description":"RNA-seq of human stem cell-derived astrocytes carrying OPTN(E50K), from the study of non-cell-autonomous contributions to ganglion cell degeneration. Complements the ganglion-cell dataset above by covering the glial side of the same genotype.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[8],"sample_count":8,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:35714595"],"publication_contexts":[{"context_id":"disorder:OPTN-related_Open_Angle_Glaucoma","publication":"PMID:35714595"}],"publication":"PMID:35714595","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35714595","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located by GEO DataSets search on \"optineurin E50K\"; accession, title, sample count and organism are GEO's own values, retrieved 2026-08-20. Note that the astrocyte arm is NOT modeled in this entry's pathophysiology, which is curated as a cell-autonomous ganglion cell lesion; a non-cell-autonomous glial contribution is plausible but not yet curated here. Carries no evidence block for the same reason as the record above."],"contexts":[{"id":"disorder:OPTN-related_Open_Angle_Glaucoma","name":"OPTN-related Open Angle Glaucoma","kind":"Disorder","source_path":"kb/disorders/OPTN-related_Open_Angle_Glaucoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/OPTN-related_Open_Angle_Glaucoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/OPTN-related_Open_Angle_Glaucoma.html#dataset-geo-gse173129"}],"context_names":["OPTN-related Open Angle Glaucoma"],"disease_names":["OPTN-related Open Angle Glaucoma"],"disease_name":"OPTN-related Open Angle Glaucoma","same_context_model_ids":["model:kb/disorders/OPTN-related_Open_Angle_Glaucoma.yaml:Isogenic OPTN(E50K) human pluripotent stem cell-derived retinal ganglion cells"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/OPTN-related_Open_Angle_Glaucoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/OPTN-related_Open_Angle_Glaucoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/OPTN-related_Open_Angle_Glaucoma.html#dataset-geo-gse173129"]},{"id":"dataset:geo:gse173251","accession":"geo:GSE173251","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE173251","title":"AKT signaling contributes to neural crest cells migration in patients affected with Bosma Arhinia and Microphtalmia syndrome.","alternate_titles":[],"description":"Bulk RNA-seq of human induced-pluripotent-stem-cell-derived neural crest stem cells from BAMS, FSHD1, FSHD2, and control samples. The dataset underlies the extracellular-matrix, receptor-signaling, adhesion, and migration analysis used in the BAMS cellular mechanism.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"CL:0011012","label":"neural crest cell","display_label":"neural crest cell","url":"http://purl.obolibrary.org/obo/CL_0011012"}],"sample_type_labels":["neural crest cell"],"sample_counts":[12],"sample_count":12,"conditions":["BAMS patient-derived neural crest stem cells","FSHD1 patient-derived neural crest stem cells","FSHD2 patient-derived neural crest stem cells","Control neural crest stem cells"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["Illumina HiSeq 4000"],"platform":"Illumina HiSeq 4000","publications":["PMID:34209568"],"publication_contexts":[{"context_id":"disorder:Bosma_Arhinia_Microphthalmia_Syndrome","publication":"PMID:34209568"}],"publication":"PMID:34209568","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34209568","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"url:https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE173251","reference_url":null,"reference_title":"GEO Accession viewer","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"To gain further insights into the specificity of SMCHD1 mutations and identify pathways associated with the disease phenotypes, we have derived induced pluripotent stem cells from patients affected with BAMS or FSHD. We then differentiated these cells into neural crest stem cells, corresponding to the cell type that is mainly affected in BAMS and analyzed their transcriptome by RNA Seq.","explanation":"The GEO record supplies the accession, organism, cell model, disease comparisons, and assay."}],"notes":[],"contexts":[{"id":"disorder:Bosma_Arhinia_Microphthalmia_Syndrome","name":"Bosma Arhinia Microphthalmia Syndrome","kind":"Disorder","source_path":"kb/disorders/Bosma_Arhinia_Microphthalmia_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bosma_Arhinia_Microphthalmia_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Bosma_Arhinia_Microphthalmia_Syndrome.html#dataset-geo-gse173251"}],"context_names":["Bosma Arhinia Microphthalmia Syndrome"],"disease_names":["Bosma Arhinia Microphthalmia Syndrome"],"disease_name":"Bosma Arhinia Microphthalmia Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Bosma_Arhinia_Microphthalmia_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bosma_Arhinia_Microphthalmia_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Bosma_Arhinia_Microphthalmia_Syndrome.html#dataset-geo-gse173251"]},{"id":"dataset:geo:gse173665","accession":"geo:GSE173665","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE173665","title":"Brain transcriptome analysis of a TPP-1 neuronal ceroid lipofuscinosis mouse model as disease progresses","alternate_titles":[],"description":"We analyzed expression changes in the Tpp1-/- forebrain/midbrain and cerebellum of 1, 2, and 3 mo. mutants compared to strain-related controls RNA-sequencing technology.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[36],"sample_count":36,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:34749772"],"publication_contexts":[{"context_id":"disorder:Neuronal_Ceroid_Lipofuscinosis","publication":"PMID:34749772"}],"publication":"PMID:34749772","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34749772","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Neuronal Ceroid Lipofuscinosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Neuronal_Ceroid_Lipofuscinosis","name":"Neuronal Ceroid Lipofuscinosis","kind":"Disorder","source_path":"kb/disorders/Neuronal_Ceroid_Lipofuscinosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Neuronal_Ceroid_Lipofuscinosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Neuronal_Ceroid_Lipofuscinosis.html#dataset-geo-gse173665"}],"context_names":["Neuronal Ceroid Lipofuscinosis"],"disease_names":["Neuronal Ceroid Lipofuscinosis"],"disease_name":"Neuronal Ceroid Lipofuscinosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Neuronal_Ceroid_Lipofuscinosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Neuronal_Ceroid_Lipofuscinosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Neuronal_Ceroid_Lipofuscinosis.html#dataset-geo-gse173665"]},{"id":"dataset:geo:gse174367","accession":"geo:GSE174367","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE174367","title":"Single-nucleus chromatin accessibility and transcriptomic characterization of Alzheimer's Disease","alternate_titles":[],"description":"Paired single-nucleus RNA-seq and ATAC-seq of human Alzheimer cortex, so expression changes can be checked against chromatin accessibility in the same cell types.","alternate_descriptions":[],"data_types":["MULTI_OMICS"],"data_type_labels":["Multi Omics"],"data_type_label":"Multi Omics","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"Homo sapiens","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0000956","label":"cerebral cortex","display_label":"cerebral cortex","url":"http://purl.obolibrary.org/obo/UBERON_0000956"}],"sample_type_labels":["cerebral cortex"],"sample_counts":[230],"sample_count":230,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:34239132"],"publication_contexts":[{"context_id":"disorder:Alzheimer_Disease","publication":"PMID:34239132"}],"publication":"PMID:34239132","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34239132","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["The paired assay is what makes this dataset useful beyond replication: it allows a senescence or necroptosis expression claim to be tested for regulatory support rather than transcript abundance alone. Accession resolved against the GEO API with `just verify-datasets`."],"contexts":[{"id":"disorder:Alzheimer_Disease","name":"Alzheimer Disease","kind":"Disorder","source_path":"kb/disorders/Alzheimer_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alzheimer_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Alzheimer_Disease.html#dataset-geo-gse174367"}],"context_names":["Alzheimer Disease"],"disease_names":["Alzheimer Disease"],"disease_name":"Alzheimer Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Alzheimer_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alzheimer_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Alzheimer_Disease.html#dataset-geo-gse174367"]},{"id":"dataset:geo:gse174376","accession":"geo:GSE174376","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE174376","title":"A single-cell/nucleus atlas of pediatric rhabdomyosarcoma","alternate_titles":[],"description":"Comprehensive single-cell atlas (122,731 nuclei/cells) from 18 primary patient tumors (6 ARMS + 12 ERMS), 18 orthotopic PDX models, and organoids. Multi-modal: snRNA-seq (frozen tumors), scRNA-seq (fresh), scATAC-seq (paired chromatin accessibility), and lentiviral barcode lineage tracking. Defines a 3-state myogenic developmental hierarchy (progenitor / myoblast-like / myocyte-like) shared across subtypes. ARMS shows a narrower late-stage developmental bias vs. ERMS. scATAC-seq links chromatin accessibility to cell-state transitions. Chemotherapy selects for ABCG2+ mesoderm-like quiescent progenitor cells, providing a mechanistic model for disease relapse. Includes matched pre/post-treatment samples from RMS13 clinical trial.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0001134","label":"skeletal muscle tissue","display_label":"skeletal muscle tissue","url":"http://purl.obolibrary.org/obo/UBERON_0001134"}],"sample_type_labels":["skeletal muscle tissue"],"sample_counts":[64],"sample_count":64,"conditions":["alveolar rhabdomyosarcoma (ARMS)","embryonal rhabdomyosarcoma (ERMS)","treatment-naive","post-chemotherapy"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["10x Genomics Chromium; Illumina HiSeq 4000/NovaSeq"],"platform":"10x Genomics Chromium; Illumina HiSeq 4000/NovaSeq","publications":["PMID:35483358"],"publication_contexts":[{"context_id":"disorder:Alveolar_Rhabdomyosarcoma","publication":"PMID:35483358"}],"publication":"PMID:35483358","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35483358","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:35483358","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/35483358","reference_title":"The myogenesis program drives clonal selection and drug resistance in rhabdomyosarcoma.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Here, we use single-cell and single-nucleus RNA sequencing to show that RMS tumors recapitulate the spectrum of embryonal myogenesis.","explanation":"Supports the principal single-cell and single-nucleus dataset design; ARMS-specific sample composition is accession metadata rather than a claim established by this abstract sentence."}],"notes":["GEO series GSE174376. Uniformly processed open-access downloads available via ScPCA project SCPCP000005 (Alex's Lemonade Stand Foundation) as SingleCellExperiment and AnnData objects. The paired scATAC-seq (6 samples) is the only publicly available chromatin-accessibility data from primary human ARMS patient tissue."],"contexts":[{"id":"disorder:Alveolar_Rhabdomyosarcoma","name":"Alveolar Rhabdomyosarcoma","kind":"Disorder","source_path":"kb/disorders/Alveolar_Rhabdomyosarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alveolar_Rhabdomyosarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Alveolar_Rhabdomyosarcoma.html#dataset-geo-gse174376"}],"context_names":["Alveolar Rhabdomyosarcoma"],"disease_names":["Alveolar Rhabdomyosarcoma"],"disease_name":"Alveolar Rhabdomyosarcoma","same_context_model_ids":["model:kb/disorders/Alveolar_Rhabdomyosarcoma.yaml:Fusion-positive RMS cancer-associated fibroblast coculture","model:kb/disorders/Alveolar_Rhabdomyosarcoma.yaml:Patient-derived ARMS single-cell culture model"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Alveolar_Rhabdomyosarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alveolar_Rhabdomyosarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Alveolar_Rhabdomyosarcoma.html#dataset-geo-gse174376"]},{"id":"dataset:geo:gse174600","accession":"geo:GSE174600","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE174600","title":"Deficiency of intellectual disability-related gene Brpf1 attenuated hippocampal excitatory neurotransmission and impaired learning and memory behavior","alternate_titles":[],"description":"Bulk RNA sequencing after Brpf1 knockdown in primary mouse hippocampal cultures and in stereotactically injected hippocampal CA1 tissue.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"Mus musculus","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":["Hippocampal neuron culture, scramble control","Hippocampal neuron culture, Brpf1 shRNA","Hippocampal CA1 tissue, scramble control","Hippocampal CA1 tissue, Brpf1 shRNA"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["Illumina HiSeq 2500 (GPL17021)"],"platform":"Illumina HiSeq 2500 (GPL17021)","publications":["PMID:34485298"],"publication_contexts":[{"context_id":"disorder:BRPF1-Related_Intellectual_Disability","publication":"PMID:34485298"}],"publication":"PMID:34485298","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34485298","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["GEO records three samples per condition. The paper describes three pairs of samples for each preparation. Culture and tissue contrasts must be analyzed separately; neither is a human heterozygous transcriptome."],"contexts":[{"id":"disorder:BRPF1-Related_Intellectual_Disability","name":"BRPF1-Related Intellectual Disability","kind":"Disorder","source_path":"kb/disorders/BRPF1-Related_Intellectual_Disability.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/BRPF1-Related_Intellectual_Disability.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/BRPF1-Related_Intellectual_Disability.html#dataset-geo-gse174600"}],"context_names":["BRPF1-Related Intellectual Disability"],"disease_names":["BRPF1-Related Intellectual Disability"],"disease_name":"BRPF1-Related Intellectual Disability","same_context_model_ids":["model:kb/disorders/BRPF1-Related_Intellectual_Disability.yaml:BRPF1 Pro370Ser patient-derived lymphoblastoid cells","model:kb/disorders/BRPF1-Related_Intellectual_Disability.yaml:Brpf1-knockdown mouse hippocampal neuron cultures","model:kb/disorders/BRPF1-Related_Intellectual_Disability.yaml:Brpf1-knockdown mouse MGE-derived interneuron cultures","model:kb/disorders/BRPF1-Related_Intellectual_Disability.yaml:Brpf1-null fetal-liver and neonatal marrow colony cultures","model:kb/disorders/BRPF1-Related_Intellectual_Disability.yaml:BRPF1-null human H1 embryonic stem cells with inducible rescue","model:kb/disorders/BRPF1-Related_Intellectual_Disability.yaml:Emx1-lineage Brpf1 conditional cortical neuron cultures","model:kb/disorders/BRPF1-Related_Intellectual_Disability.yaml:Inducible Brpf1-null mouse embryonic fibroblasts"],"candidate_model_ids":["model:kb/disorders/BRPF1-Related_Intellectual_Disability.yaml:Brpf1-knockdown mouse hippocampal neuron cultures"],"association_basis":"Same publication as a NAM (candidate)","nam_disease_context":"Same publication as a NAM (candidate)","source_paths":["kb/disorders/BRPF1-Related_Intellectual_Disability.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/BRPF1-Related_Intellectual_Disability.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/BRPF1-Related_Intellectual_Disability.html#dataset-geo-gse174600"]},{"id":"dataset:geo:gse174804","accession":"geo:GSE174804","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE174804","title":"Ex vivo scRNA-Seq of CD4+ cells in T-bet deficiency and wild type","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:34160550"],"publication_contexts":[{"context_id":"disorder:Immunodeficiency_88","publication":"PMID:34160550"}],"publication":"PMID:34160550","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34160550","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Single-cell transcriptomes of CD4+ T cells from the T-bet-deficient patient and wild-type controls, generated for the Th2/upper-airway-inflammation study. Relevance was triaged manually: the candidate was surfaced by a TBX21 gene-only search, which returned mostly mouse and cancer datasets about unrelated T-bet biology, but this accession is from the companion study of this disease's index patient."],"contexts":[{"id":"disorder:Immunodeficiency_88","name":"Immunodeficiency 88","kind":"Disorder","source_path":"kb/disorders/Immunodeficiency_88.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Immunodeficiency_88.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Immunodeficiency_88.html#dataset-geo-gse174804"}],"context_names":["Immunodeficiency 88"],"disease_names":["Immunodeficiency 88"],"disease_name":"Immunodeficiency 88","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Immunodeficiency_88.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Immunodeficiency_88.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Immunodeficiency_88.html#dataset-geo-gse174804"]},{"id":"dataset:geo:gse17536","accession":"geo:GSE17536","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE17536","title":"Metastasis Gene Expression Profile Predicts Recurrence and Death in Colon Cancer Patients (Moffitt Samples)","alternate_titles":[],"description":"Independent validation cohort of 177 colon cancer samples from Moffitt Cancer Center with clinical outcome data including metastasis risk and survival information.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0001155","label":"colon","display_label":"colon tumor tissue","url":"http://purl.obolibrary.org/obo/UBERON_0001155"}],"sample_type_labels":["colon"],"sample_counts":[177],"sample_count":177,"conditions":["colon cancer (various stages)"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:19914252"],"publication_contexts":[{"context_id":"disorder:Lynch_Syndrome","publication":"PMID:19914252"}],"publication":"PMID:19914252","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/19914252","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:19914252","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/19914252","reference_title":"Experimentally derived metastasis gene expression profile predicts recurrence and death in patients with colon cancer.","supports":"SUPPORT","evidence_source":null,"snippet":"This phase 1, exploratory biomarker study used 55 patients with colorectal cancer from Vanderbilt Medical Center (VMC) as the training dataset and 177 patients from the Moffitt Cancer Center as the independent dataset.","explanation":"This directly supports the Moffitt cohort sample count and study context represented in this dataset entry."}],"notes":["Used with GSE39582 for validation of molecular classifiers. Contains stage information useful for prognostic analysis"],"contexts":[{"id":"disorder:Lynch_Syndrome","name":"Lynch Syndrome","kind":"Disorder","source_path":"kb/disorders/Lynch_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Lynch_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Lynch_Syndrome.html#dataset-geo-gse17536"}],"context_names":["Lynch Syndrome"],"disease_names":["Lynch Syndrome"],"disease_name":"Lynch Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Lynch_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Lynch_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Lynch_Syndrome.html#dataset-geo-gse17536"]},{"id":"dataset:geo:gse175386","accession":"geo:GSE175386","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE175386","title":"Tumor cells in light-chain amyloidosis and multiple myeloma show different transcriptional rewiring of the normal plasma cell development","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[141],"sample_count":141,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:34133718"],"publication_contexts":[{"context_id":"disorder:AL_Amyloidosis","publication":"PMID:34133718"}],"publication":"PMID:34133718","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34133718","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Systemic AL Amyloidosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:AL_Amyloidosis","name":"Systemic AL Amyloidosis","kind":"Disorder","source_path":"kb/disorders/AL_Amyloidosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/AL_Amyloidosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Systemic_AL_Amyloidosis.html#dataset-geo-gse175386"}],"context_names":["Systemic AL Amyloidosis"],"disease_names":["Systemic AL Amyloidosis"],"disease_name":"Systemic AL Amyloidosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/AL_Amyloidosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/AL_Amyloidosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Systemic_AL_Amyloidosis.html#dataset-geo-gse175386"]},{"id":"dataset:geo:gse176510","accession":"geo:GSE176510","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE176510","title":"Evaluation of immune pathways in the conjunctiva of Sjogren Syndrome keratoconjunctivitis sicca","alternate_titles":[],"description":"After signing the informed consent, female SS patients (n = 7) and age-and-sex-matched healthy controls (n = 19) completed a series of oral, ocular surface exams. Symptom severity scores were evaluated using validated questionnaires (OSDI and SANDE). All patients fulfilled the ACR/EULAR criteria for SS and the criteria for KCS. Tear meniscus height was measured by optical coherence tomography. Fluorescein and lissamine green dye staining evaluated tear-break-up time (TBUT), corneal and conjunctival disease, respectively. Impression cytology of the temporal bulbar conjunctiva was performed using the Eyeprim™ device.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[26],"sample_count":26,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Sjogren's Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Sjogrens_Syndrome","name":"Sjogren's Syndrome","kind":"Disorder","source_path":"kb/disorders/Sjogrens_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sjogrens_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Sjogren's_Syndrome.html#dataset-geo-gse176510"}],"context_names":["Sjogren's Syndrome"],"disease_names":["Sjogren's Syndrome"],"disease_name":"Sjogren's Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Sjogrens_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sjogrens_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Sjogren's_Syndrome.html#dataset-geo-gse176510"]},{"id":"dataset:geo:gse177044","accession":"geo:GSE177044","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE177044","title":"Large-scale whole blood RNA-Seq identifies transcriptional differences between primary sclerosing cholangitis and ulcerative colitis","alternate_titles":[],"description":"Background: Patients suffering from primary sclerosing cholangitis (PSC) often also have ulcerative colitis (UC). Cross-disease genetic and microbiome studies across PSC und UC patients indicated that UC in PSC is a separate disease entity from primary UC, but expression studies for PSC are lacking. In this study, we performed a molecular comparison of whole blood expression levels in PSC only, PSC patients with additional UC diagnosis (PSC/UC), and UC, using a large collection of whole blood transcriptome data. Methods: We conducted whole blood RNA-Seq experiments for 495 UC patients, 220 PSC patients (of whom 177 have also a UC diagnosis), and 320 healthy controls from Germany and Norway.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[1035],"sample_count":1035,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:38304234"],"publication_contexts":[{"context_id":"disorder:Primary_Sclerosing_Cholangitis","publication":"PMID:38304234"},{"context_id":"disorder:Sclerosing_Cholangitis","publication":"PMID:38304234"}],"publication":"PMID:38304234","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38304234","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Primary Sclerosing Cholangitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.","Identified by GEO DataSets index search for Sclerosing Cholangitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Primary_Sclerosing_Cholangitis","name":"Primary Sclerosing Cholangitis","kind":"Disorder","source_path":"kb/disorders/Primary_Sclerosing_Cholangitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Primary_Sclerosing_Cholangitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Sclerosing_Cholangitis.html#dataset-geo-gse177044"},{"id":"disorder:Sclerosing_Cholangitis","name":"Sclerosing Cholangitis","kind":"Disorder","source_path":"kb/disorders/Sclerosing_Cholangitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sclerosing_Cholangitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Sclerosing_Cholangitis.html#dataset-geo-gse177044"}],"context_names":["Primary Sclerosing Cholangitis","Sclerosing Cholangitis"],"disease_names":["Primary Sclerosing Cholangitis","Sclerosing Cholangitis"],"disease_name":"Primary Sclerosing Cholangitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Primary_Sclerosing_Cholangitis.yaml","kb/disorders/Sclerosing_Cholangitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Primary_Sclerosing_Cholangitis.yaml","https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sclerosing_Cholangitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Primary_Sclerosing_Cholangitis.html#dataset-geo-gse177044","https://dismech.monarchinitiative.org/pages/disorders/Sclerosing_Cholangitis.html#dataset-geo-gse177044"]},{"id":"dataset:geo:gse177522","accession":"geo:GSE177522","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE177522","title":"RNA-Seq analysis of human MEN1-associated thymic carcinoid and thymoma compared to normal thymus","alternate_titles":[],"description":"RNA-Sequencing was performed on rRNA-depleted RNA samples that were isolated from formalin fixed paraffin embedded (FFPE) tissue sections of human normal thymus and human thymic tumors of patients with multiple endocrine neoplasia type 1 (MEN1) syndrome.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[19],"sample_count":19,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:34515662"],"publication_contexts":[{"context_id":"disorder:Thymoma","publication":"PMID:34515662"}],"publication":"PMID:34515662","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34515662","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Thymoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Thymoma","name":"Thymoma","kind":"Disorder","source_path":"kb/disorders/Thymoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Thymoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Thymoma.html#dataset-geo-gse177522"}],"context_names":["Thymoma"],"disease_names":["Thymoma"],"disease_name":"Thymoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Thymoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Thymoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Thymoma.html#dataset-geo-gse177522"]},{"id":"dataset:geo:gse178126","accession":"geo:GSE178126","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE178126","title":"Circulating miRNA profile and coronary calcification in asymptomatic patients with familial hypercholesterolemia.","alternate_titles":[],"description":"Microarray profiling of plasma microRNAs in asymptomatic familial hypercholesterolemia patients stratified by coronary artery calcium score on computed tomographic angiography. Relevant to the subclinical phase of the arterial arm - patients who already carry the lifelong LDL burden but have not yet had an event. Relevance caveat: the cohort is defined clinically and the series does not report LDLR genotypes, so it is class-level rather than LDLR-specific.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:38513437"],"publication_contexts":[{"context_id":"disorder:LDLR-Related_Familial_Hypercholesterolemia","publication":"PMID:38513437"}],"publication":"PMID:38513437","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38513437","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE178126","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE178126","reference_title":"Circulating miRNA profile and coronary calcification in asymptomatic patients with familial hypercholesterolemia.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"We used miRNA arrays to profile miRNAs isolated from plasma from familial hypercholesterolemia patients with (FH-W_CCS) or without (FH-WO_CCS) coronary calcium score by computed tomographic angiography","explanation":"The repository record's own statement of the stratification, which is what makes this series about the subclinical arterial phase rather than about FH generally."}],"notes":["Surfaced by `just discover-datasets` as a DIRECT candidate and confirmed against the linked publication before inclusion."],"contexts":[{"id":"disorder:LDLR-Related_Familial_Hypercholesterolemia","name":"LDLR-Related Familial Hypercholesterolemia","kind":"Disorder","source_path":"kb/disorders/LDLR-Related_Familial_Hypercholesterolemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/LDLR-Related_Familial_Hypercholesterolemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/LDLR-Related_Familial_Hypercholesterolemia.html#dataset-geo-gse178126"}],"context_names":["LDLR-Related Familial Hypercholesterolemia"],"disease_names":["LDLR-Related Familial Hypercholesterolemia"],"disease_name":"LDLR-Related Familial Hypercholesterolemia","same_context_model_ids":["model:kb/disorders/LDLR-Related_Familial_Hypercholesterolemia.yaml:Activity-normalized prime editing saturation screen of LDLR coding variants","model:kb/disorders/LDLR-Related_Familial_Hypercholesterolemia.yaml:CHO-ldlA7 heterologous LDLR variant expression assay","model:kb/disorders/LDLR-Related_Familial_Hypercholesterolemia.yaml:J.D. fibroblast strain (internalization-defective LDLR alleles)","model:kb/disorders/LDLR-Related_Familial_Hypercholesterolemia.yaml:JD iPSC-derived hepatocyte-like cells"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/LDLR-Related_Familial_Hypercholesterolemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/LDLR-Related_Familial_Hypercholesterolemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/LDLR-Related_Familial_Hypercholesterolemia.html#dataset-geo-gse178126"]},{"id":"dataset:geo:gse178240","accession":"geo:GSE178240","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE178240","title":"A population of CD4+CD8+ double-positive T cells associated with risk of plasma leakage in dengue viral infection","alternate_titles":[],"description":"According to the WHO 2009 classification, dengue with warning signs (D+W) is at the risk of developing severe form of dengue disease. One of the most important warning signs is plasma leakage, which is a serious complication associated with higher morbidity and mortality. We report that the frequency of CD4+CD8+ double-positive (DP) T cells is significantly increased in patients at risk of developing plasma leakage. Transcriptomic analysis demonstrated that CD4+CD8+ DP cells were distinct from CD4+ Single Positive (SP) T cells, but co-clustered with CD8+ SP cells indicating a largely similar transcriptional profile.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[414],"sample_count":414,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:35062294"],"publication_contexts":[{"context_id":"disorder:Dengue","publication":"PMID:35062294"}],"publication":"PMID:35062294","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35062294","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Dengue (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Dengue","name":"Dengue","kind":"Disorder","source_path":"kb/disorders/Dengue.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dengue.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Dengue.html#dataset-geo-gse178240"}],"context_names":["Dengue"],"disease_names":["Dengue"],"disease_name":"Dengue","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Dengue.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dengue.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Dengue.html#dataset-geo-gse178240"]},{"id":"dataset:geo:gse178304","accession":"geo:GSE178304","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE178304","title":"Ageing-associated myelin dysfunction drives amyloid deposition in mouse models of Alzheimer's disease","alternate_titles":[],"description":"SuperSeries of mouse single-nucleus and bulk transcriptomics testing whether myelin dysfunction drives amyloid deposition, including grey versus white matter under myelin abnormality and microglial profiling on a 5xFAD background.","alternate_descriptions":[],"data_types":["MULTI_OMICS"],"data_type_labels":["Multi Omics"],"data_type_label":"Multi Omics","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"Mus musculus","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[30],"sample_count":30,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37258678"],"publication_contexts":[{"context_id":"disorder:Alzheimer_Disease","publication":"PMID:37258678"}],"publication":"PMID:37258678","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37258678","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Mouse only, and deliberately curated as such: this is the data establishing the causal direction (myelin dysfunction to amyloid) that no human observational dataset can establish, and it is the pairing partner for the human oligodendrocyte arm. The human counterpart from the APOE4-myelination work (PMID:36385529) is Synapse syn38120890 and is fully controlled-access with no GEO deposit, so SEA-AD's open oligodendrocyte matrices are the practical human arm instead. Accession resolved against the GEO API with `just verify-datasets`."],"contexts":[{"id":"disorder:Alzheimer_Disease","name":"Alzheimer Disease","kind":"Disorder","source_path":"kb/disorders/Alzheimer_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alzheimer_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Alzheimer_Disease.html#dataset-geo-gse178304"}],"context_names":["Alzheimer Disease"],"disease_names":["Alzheimer Disease"],"disease_name":"Alzheimer Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Alzheimer_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alzheimer_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Alzheimer_Disease.html#dataset-geo-gse178304"]},{"id":"dataset:geo:gse178491","accession":"geo:GSE178491","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE178491","title":"An AI-guided invariant signature places MIS-C with Kawasaki disease in a continuum of host immune responses","alternate_titles":[],"description":"A significant surge in cases of multisystem inflammatory syndrome in children (MIS-C, also called Pediatric Inflammatory Multisystem Syndrome - PIMS) has been observed amidst the COVID-19 pandemic. MIS-C shares many clinical features with Kawasaki disease (KD), although clinical course and outcomes are divergent. We analyzed whole blood RNA sequences, serum cytokines, and formalin fixed heart tissues from these patients using a computational toolbox of two gene signatures, i.e., viral pandemic (ViP), and a subset of it called, severe (s)ViP signatures that were developed in the context of SARS-CoV-2 infection in COVID-19 and a 13-transcript signature previously demonstrated to be diagnostic...","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[191],"sample_count":191,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:35577777"],"publication_contexts":[{"context_id":"disorder:Kawasaki_Disease","publication":"PMID:35577777"}],"publication":"PMID:35577777","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35577777","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Kawasaki Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Kawasaki_Disease","name":"Kawasaki Disease","kind":"Disorder","source_path":"kb/disorders/Kawasaki_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Kawasaki_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Kawasaki_Disease.html#dataset-geo-gse178491"}],"context_names":["Kawasaki Disease"],"disease_names":["Kawasaki Disease"],"disease_name":"Kawasaki Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Kawasaki_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Kawasaki_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Kawasaki_Disease.html#dataset-geo-gse178491"]},{"id":"dataset:geo:gse178501","accession":"geo:GSE178501","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE178501","title":"MicroRNA (miRNA) Expression in Circulating Leukocytes and Bioinformatic Analysis of Patients with Moyamoya Disease (MMD)","alternate_titles":[],"description":"To investigate the differential expression of miRNAs in circulating leukocytes of patients with MMD. The results showed 12 differentially expressed miRNAs in leukocytes of MMD patients compared with controls (fold change > 2.0 and P < 0.05), of which 7 were up-regulated and 5 were down-regulated.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[40],"sample_count":40,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:35669195"],"publication_contexts":[{"context_id":"disorder:Moyamoya_Disease","publication":"PMID:35669195"}],"publication":"PMID:35669195","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35669195","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Moyamoya Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Moyamoya_Disease","name":"Moyamoya Disease","kind":"Disorder","source_path":"kb/disorders/Moyamoya_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Moyamoya_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Moyamoya_Disease.html#dataset-geo-gse178501"}],"context_names":["Moyamoya Disease"],"disease_names":["Moyamoya Disease"],"disease_name":"Moyamoya Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Moyamoya_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Moyamoya_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Moyamoya_Disease.html#dataset-geo-gse178501"]},{"id":"dataset:geo:gse178563","accession":"geo:GSE178563","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE178563","title":"Transcriptome analysis of the host immune responses to Sarcoptes scabiei","alternate_titles":[],"description":"Scabies is a human skin disease due to the burrowing ectoparasite Sarcoptes scabiei resulting in intense itching and inflammation and manifesting as skin allergy. Little is known about the specific scabies molecules and genes involved in the host inflammatory and immunologic responses. We interrogated the transcriptome profiles of skin biopsies using next generation sequencing and a combined clustering and pathway mapping approach which will enable us in the identification of key signaling events in the host immune and inflammatory responses to S. scabiei infestation. With the comprehensive analysis of RNA-seq results, it has been found that the immune response of host inhibits S.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[8],"sample_count":8,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:34925353"],"publication_contexts":[{"context_id":"disorder:Scabies","publication":"PMID:34925353"}],"publication":"PMID:34925353","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34925353","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Scabies (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Scabies","name":"Scabies","kind":"Disorder","source_path":"kb/disorders/Scabies.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Scabies.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Scabies.html#dataset-geo-gse178563"}],"context_names":["Scabies"],"disease_names":["Scabies"],"disease_name":"Scabies","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Scabies.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Scabies.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Scabies.html#dataset-geo-gse178563"]},{"id":"dataset:geo:gse178925","accession":"geo:GSE178925","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE178925","title":"Genome-wide DNA methylation analysis of gastric mucosa with autoimmune gastritis","alternate_titles":[],"description":"DNA methylation in gastric mucosa with autoimmune gastritis and H. pylori-associated gastritis and normal gastric mucosa","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[24],"sample_count":24,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:35034200"],"publication_contexts":[{"context_id":"disorder:Autoimmune_Gastritis","publication":"PMID:35034200"}],"publication":"PMID:35034200","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35034200","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Autoimmune Gastritis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Autoimmune_Gastritis","name":"Autoimmune Gastritis","kind":"Disorder","source_path":"kb/disorders/Autoimmune_Gastritis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autoimmune_Gastritis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autoimmune_Gastritis.html#dataset-geo-gse178925"}],"context_names":["Autoimmune Gastritis"],"disease_names":["Autoimmune Gastritis"],"disease_name":"Autoimmune Gastritis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Autoimmune_Gastritis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autoimmune_Gastritis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Autoimmune_Gastritis.html#dataset-geo-gse178925"]},{"id":"dataset:geo:gse179221","accession":"geo:GSE179221","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE179221","title":"Aberrant extrafollicular B cells, immune dysfunction and myeloid inflammation precede malignancy in Waldenstrom macroglobulinemia","alternate_titles":[],"description":"Waldenstrom macroglobulinemia (WM) and its precursor IgM gammopathy are distinct disorders characterized by the growth of mature IgM-expressing B cell clone predominantly in the bone marrow. Here we show that these disorders originate in the setting of expansion of genomically aberrant extrafollicular B cells, immune dysfunction and myeloid inflammation that begins before the expansion of the malignant clone. Host response to these early lesions involves the induction of tumor-specific T cell immunity that may include MYD88 mutation-specific responses. Hematopoietic progenitors carry the oncogenic MYD88 mutations characteristic of the malignant WM clone.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[18],"sample_count":18,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:34778800"],"publication_contexts":[{"context_id":"disorder:Waldenstrom_Macroglobulinemia","publication":"PMID:34778800"}],"publication":"PMID:34778800","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34778800","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Waldenstrom Macroglobulinemia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Waldenstrom_Macroglobulinemia","name":"Waldenstrom Macroglobulinemia","kind":"Disorder","source_path":"kb/disorders/Waldenstrom_Macroglobulinemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Waldenstrom_Macroglobulinemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Waldenstrom_Macroglobulinemia.html#dataset-geo-gse179221"}],"context_names":["Waldenstrom Macroglobulinemia"],"disease_names":["Waldenstrom Macroglobulinemia"],"disease_name":"Waldenstrom Macroglobulinemia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Waldenstrom_Macroglobulinemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Waldenstrom_Macroglobulinemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Waldenstrom_Macroglobulinemia.html#dataset-geo-gse179221"]},{"id":"dataset:geo:gse179384","accession":"geo:GSE179384","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE179384","title":"The ribose methylation enzyme FTSJ1 has a conserved role in neuron morphology and learning performance","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[9],"sample_count":9,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:13254","label":"FTSJ1","display_label":"FTSJ1","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/13254"}],"genes":["FTSJ1"],"platforms":[],"platform":null,"publications":["PMID:36720500"],"publication_contexts":[{"context_id":"disorder:Non-Syndromic_X-Linked_Intellectual_Disability","publication":"PMID:36720500"}],"publication":"PMID:36720500","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36720500","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Human lymphoblastoid material from patients with FTSJ1 loss of function, supporting the MRX9 subtype and the tRNA-modification arm of the convergence node. Selected by relevance triage from the dataset-discovery candidates as the only DIRECT (disease-named, human, primary-material) hit; the remaining candidates were GENE_ONLY matches whose biology is unrelated to this disease (for example TSPAN7 in pancreatic beta-cell exocytosis, GDI1 in yeast Ypt1 trafficking) and were rejected. No evidence block is attached, per the dataset-curation SOP."],"contexts":[{"id":"disorder:Non-Syndromic_X-Linked_Intellectual_Disability","name":"Non-Syndromic X-Linked Intellectual Disability","kind":"Disorder","source_path":"kb/disorders/Non-Syndromic_X-Linked_Intellectual_Disability.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Non-Syndromic_X-Linked_Intellectual_Disability.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Non-Syndromic_X-Linked_Intellectual_Disability.html#dataset-geo-gse179384"}],"context_names":["Non-Syndromic X-Linked Intellectual Disability"],"disease_names":["Non-Syndromic X-Linked Intellectual Disability"],"disease_name":"Non-Syndromic X-Linked Intellectual Disability","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Non-Syndromic_X-Linked_Intellectual_Disability.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Non-Syndromic_X-Linked_Intellectual_Disability.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Non-Syndromic_X-Linked_Intellectual_Disability.html#dataset-geo-gse179384"]},{"id":"dataset:geo:gse179468","accession":"geo:GSE179468","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE179468","title":"Functional characterization of the transcription programs underlying phase transition in the BSL3 pathogen Coccidioides immitis","alternate_titles":[],"description":"Capped small RNA-seq of Coccidioides immitis across the mycelium-to-spherule phase transition, profiling the transcriptional reprogramming that underlies the morphogenesis step at the head of this entry's pathograph. Includes comparator fungal species used in the analysis.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:5501","label":"Coccidioides immitis","display_label":"Coccidioides immitis","url":"http://purl.obolibrary.org/obo/NCBITaxon_5501"}],"organism_labels":["Coccidioides immitis"],"organism_label":"Coccidioides immitis","sample_types":[],"sample_type_labels":[],"sample_counts":[27],"sample_count":27,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:35076277"],"publication_contexts":[{"context_id":"disorder:Coccidioidomycosis","publication":"PMID:35076277"}],"publication":"PMID:35076277","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35076277","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Coccidioidomycosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities. GEO lists four organisms for this series (Schizosaccharomyces pombe; Saccharomyces cerevisiae; Agaricus bisporus; Coccidioides immitis); the pathogen of interest is recorded here."],"contexts":[{"id":"disorder:Coccidioidomycosis","name":"Coccidioidomycosis","kind":"Disorder","source_path":"kb/disorders/Coccidioidomycosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Coccidioidomycosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Coccidioidomycosis.html#dataset-geo-gse179468"}],"context_names":["Coccidioidomycosis"],"disease_names":["Coccidioidomycosis"],"disease_name":"Coccidioidomycosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Coccidioidomycosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Coccidioidomycosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Coccidioidomycosis.html#dataset-geo-gse179468"]},{"id":"dataset:geo:gse179508","accession":"geo:GSE179508","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE179508","title":"Transcriptomic Repositioning Analysis Identifies mTOR Inhibitor as Potential Therapy for Epidermolysis Bullosa Simplex","alternate_titles":[],"description":"Human bulk RNA-seq dataset profiling blistered and non-blistered EBS skin, used to define disease-associated signaling programs and prioritize repositionable therapies.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[20],"sample_count":20,"conditions":["blistered EBS skin","non-blistered EBS skin"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE179508","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE179508","reference_title":"Transcriptomic Repositioning Analysis Identifies mTOR Inhibitor as Potential Therapy for Epidermolysis Bullosa Simplex","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"In this study, we characterize significant molecular pathways activated in the blisters that form in EBS","explanation":"Supports this GEO series as a direct transcriptomic resource for EBS lesional biology."},{"reference":"GEO:GSE179508","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE179508","reference_title":"Transcriptomic Repositioning Analysis Identifies mTOR Inhibitor as Potential Therapy for Epidermolysis Bullosa Simplex","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"We implicate the PI3K/AKT/mTOR pathway as central in the EBS disease pathway","explanation":"Confirms that the dataset captures disease-relevant signaling programs and supports downstream therapeutic inference."}],"notes":[],"contexts":[{"id":"disorder:Epidermolysis_Bullosa_Simplex","name":"Epidermolysis Bullosa Simplex","kind":"Disorder","source_path":"kb/disorders/Epidermolysis_Bullosa_Simplex.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Epidermolysis_Bullosa_Simplex.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Epidermolysis_Bullosa_Simplex.html#dataset-geo-gse179508"}],"context_names":["Epidermolysis Bullosa Simplex"],"disease_names":["Epidermolysis Bullosa Simplex"],"disease_name":"Epidermolysis Bullosa Simplex","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Epidermolysis_Bullosa_Simplex.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Epidermolysis_Bullosa_Simplex.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Epidermolysis_Bullosa_Simplex.html#dataset-geo-gse179508"]},{"id":"dataset:geo:gse179603","accession":"geo:GSE179603","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE179603","title":"Transcriptional Characterisation of Proliferative Vitreoretinopathy","alternate_titles":[],"description":"Purpose: The development of vitreoretinal scars remains an unsolved challenge in clinical practice and often leads to repeated revision surgery and blindness due to lack of efficient therapy. The aim of this study was to characterize the cellular and molecular environment in vitreoretinal scar tissue from patients with proliferative vitreoretinopathy (PVR) in comparison to membranes of the vitreoretinal junction, in order to subsequently identify potential drug treatment options using bioinformatics techniques.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[27],"sample_count":27,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:35579905"],"publication_contexts":[{"context_id":"disorder:Proliferative_Vitreoretinopathy","publication":"PMID:35579905"}],"publication":"PMID:35579905","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35579905","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Proliferative Vitreoretinopathy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Proliferative_Vitreoretinopathy","name":"Proliferative Vitreoretinopathy","kind":"Disorder","source_path":"kb/disorders/Proliferative_Vitreoretinopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Proliferative_Vitreoretinopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Proliferative_Vitreoretinopathy.html#dataset-geo-gse179603"}],"context_names":["Proliferative Vitreoretinopathy"],"disease_names":["Proliferative Vitreoretinopathy"],"disease_name":"Proliferative Vitreoretinopathy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Proliferative_Vitreoretinopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Proliferative_Vitreoretinopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Proliferative_Vitreoretinopathy.html#dataset-geo-gse179603"]},{"id":"dataset:geo:gse179720","accession":"geo:GSE179720","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE179720","title":"The   FUS-DDIT3 fusion oncoprotein inhibits BAF complex targeting and activity in myxoid liposarcoma","alternate_titles":[],"description":"Mammalian SWI/SNF (mSWI/SNF or BAF) ATP-dependent chromatin remodeling complexes play critical roles in governing genomic architecture and gene expression and are frequently perturbed in human cancers. Transcription factors (TFs), including fusion oncoproteins, can bind to BAF complex surfaces to direct chromatin targeting and accessibility, often activating oncogenic gene loci. Here, we demonstrate that the FUS-DDIT3 fusion oncoprotein hallmark to myxoid liposarcoma (MLPS) inhibits BAF complex-mediated remodeling of adipogenic enhancer sites via sequestration of the adipogenic TF, CEBPB, from the genome.","alternate_descriptions":[],"data_types":["MULTI_OMICS"],"data_type_labels":["Multi Omics"],"data_type_label":"Multi Omics","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[138],"sample_count":138,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:35390276"],"publication_contexts":[{"context_id":"disorder:Liposarcoma","publication":"PMID:35390276"}],"publication":"PMID:35390276","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35390276","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Liposarcoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Liposarcoma","name":"Liposarcoma","kind":"Disorder","source_path":"kb/disorders/Liposarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Liposarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Liposarcoma.html#dataset-geo-gse179720"}],"context_names":["Liposarcoma"],"disease_names":["Liposarcoma"],"disease_name":"Liposarcoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Liposarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Liposarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Liposarcoma.html#dataset-geo-gse179720"]},{"id":"dataset:geo:gse179730","accession":"geo:GSE179730","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE179730","title":"Response and recurrence correlates in patients treated with neoadjuvant anti-PD-1 therapy for resectable oral-cavity squamous cell carcinoma","alternate_titles":[],"description":"Neoadjuvant PD-1 blockade may be efficacious in patients with high-risk, resectable oral-cavity, head-and-neck cancer. To explore correlates of response patterns to neoadjuvant nivolumab treatment and post-surgical recurrences, we analyzed longitudinal tumor and blood samples in a cohort of 12 patients displaying 33% responsiveness. Pretreatment tumor-based detection of FLT4 mutations and PTEN signature enrichment favors response, and high tumor mutational burden improves recurrence-free survival. In contrast, preexisting and/or acquired mutations (in CDKN2A, YAP1, JAK2) correlate with innate resistance and/or tumor recurrence.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[23],"sample_count":23,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:34755131"],"publication_contexts":[{"context_id":"disorder:Oral_Cavity_Squamous_Cell_Carcinoma","publication":"PMID:34755131"}],"publication":"PMID:34755131","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34755131","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Oral Cavity Squamous Cell Carcinoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Oral_Cavity_Squamous_Cell_Carcinoma","name":"Oral Cavity Squamous Cell Carcinoma","kind":"Disorder","source_path":"kb/disorders/Oral_Cavity_Squamous_Cell_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Oral_Cavity_Squamous_Cell_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Oral_Cavity_Squamous_Cell_Carcinoma.html#dataset-geo-gse179730"}],"context_names":["Oral Cavity Squamous Cell Carcinoma"],"disease_names":["Oral Cavity Squamous Cell Carcinoma"],"disease_name":"Oral Cavity Squamous Cell Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Oral_Cavity_Squamous_Cell_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Oral_Cavity_Squamous_Cell_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Oral_Cavity_Squamous_Cell_Carcinoma.html#dataset-geo-gse179730"]},{"id":"dataset:geo:gse179900","accession":"geo:GSE179900","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE179900","title":"Modeling of lung phenotype of Hermansky-Pudlak syndrome type I using patient-specific iPS cells","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[9],"sample_count":9,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:34736469"],"publication_contexts":[{"context_id":"disorder:Hermansky_Pudlak_Syndrome","publication":"PMID:34736469"}],"publication":"PMID:34736469","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34736469","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Hermansky-Pudlak Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Hermansky_Pudlak_Syndrome","name":"Hermansky-Pudlak Syndrome","kind":"Disorder","source_path":"kb/disorders/Hermansky_Pudlak_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hermansky_Pudlak_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hermansky-Pudlak_Syndrome.html#dataset-geo-gse179900"}],"context_names":["Hermansky-Pudlak Syndrome"],"disease_names":["Hermansky-Pudlak Syndrome"],"disease_name":"Hermansky-Pudlak Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hermansky_Pudlak_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hermansky_Pudlak_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hermansky-Pudlak_Syndrome.html#dataset-geo-gse179900"]},{"id":"dataset:geo:gse180119","accession":"geo:GSE180119","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE180119","title":"DNA methylation patterns associated with cyanogenic cassava exposure and konzo in Sub-Saharan Africa","alternate_titles":[],"description":"Konzo, a disease characterized by sudden, irreversible spastic paraparesis, affecting up to 10% of the population in some regions of Sub-Saharan Africa during outbreaks and is strongly associated with dietary exposure to cyanogenic bitter cassava. The molecular mechanisms underlying the development of konzo, remain largely unknown. Here, through an analysis of 16 individuals with konzo and matched healthy controls from the same outbreak zones, we identified 117 differentially methylated loci involved in numerous biological processes that may identify cyanogenic- sensitive regions of the genome, providing the first study of epigenomic alterations associated with sub-lethal cyanide exposure an...","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[32],"sample_count":32,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:36536449"],"publication_contexts":[{"context_id":"disorder:Konzo","publication":"PMID:36536449"}],"publication":"PMID:36536449","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36536449","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Konzo (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Konzo","name":"Konzo","kind":"Disorder","source_path":"kb/disorders/Konzo.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Konzo.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Konzo.html#dataset-geo-gse180119"}],"context_names":["Konzo"],"disease_names":["Konzo"],"disease_name":"Konzo","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Konzo.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Konzo.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Konzo.html#dataset-geo-gse180119"]},{"id":"dataset:geo:gse180536","accession":"geo:GSE180536","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE180536","title":"Restored Hematopoietic Stem Cell Transcriptional Program in Fanconi Anemia Patients Following Gene Therapy","alternate_titles":[],"description":"Single-cell RNA sequencing of chimeric corrected and uncorrected HSPC populations co-existing in bone marrow of lentiviral gene therapy-treated Fanconi anemia patients. Demonstrates that gene-corrected cells revert the FA transcriptional signature to resemble healthy donor HSPCs.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["10x Genomics Chromium"],"platform":"10x Genomics Chromium","publications":["PMID:37021532"],"publication_contexts":[{"context_id":"disorder:Fanconi_Anemia","publication":"PMID:37021532"}],"publication":"PMID:37021532","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37021532","publication_status":"Publication recorded","findings":[{"statement":"Gene therapy reverts the FA HSPC transcriptional signature to healthy donor levels","evidence":[]},{"statement":"Corrected cells show downregulation of TGF-beta and p21, upregulation of DDR and telomere maintenance","evidence":[]}],"findings_text":["Gene therapy reverts the FA HSPC transcriptional signature to healthy donor levels","Corrected cells show downregulation of TGF-beta and p21, upregulation of DDR and telomere maintenance"],"evidence":[{"reference":"PMID:37021532","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/37021532","reference_title":"Gene therapy restores the transcriptional program of hematopoietic stem cells in Fanconi anemia.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"gene therapy reverts the transcriptional signature of FA HSPC, which then resemble the transcriptional program of healthy donor HSPC","explanation":"scRNA-seq of gene therapy patients confirms molecular rescue of FA-specific transcriptomic defects."}],"notes":[],"contexts":[{"id":"disorder:Fanconi_Anemia","name":"Fanconi_Anemia","kind":"Disorder","source_path":"kb/disorders/Fanconi_Anemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fanconi_Anemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Fanconi_Anemia.html#dataset-geo-gse180536"}],"context_names":["Fanconi_Anemia"],"disease_names":["Fanconi_Anemia"],"disease_name":"Fanconi_Anemia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Fanconi_Anemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fanconi_Anemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Fanconi_Anemia.html#dataset-geo-gse180536"]},{"id":"dataset:geo:gse180868","accession":"geo:GSE180868","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE180868","title":"A temporal in vivo catalog of chromatin accessibility and expression profiles in pineoblastoma reveals a prevalent role for repressor elements","alternate_titles":[],"description":"Pediatric pineoblastomas (PBs) are rare and aggressive tumors of grade IV histology. Although some oncogenic drivers are characterized, including germline mutations in RB1 and DICER1, the role of epigenetic deregulation and cis-regulatory regions in PB pathogenesis and progression is largely unknown. Here, we generated genome-wide gene expression, chromatin accessibility, and H3K27ac profiles covering key time points of PB initiation and progression from pineal tissues of a mouse model of CCND1-driven PB.","alternate_descriptions":[],"data_types":["MULTI_OMICS"],"data_type_labels":["Multi Omics"],"data_type_label":"Multi Omics","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[19],"sample_count":19,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:36650051"],"publication_contexts":[{"context_id":"disorder:Pineoblastoma","publication":"PMID:36650051"}],"publication":"PMID:36650051","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36650051","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Pineoblastoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Pineoblastoma","name":"Pineoblastoma","kind":"Disorder","source_path":"kb/disorders/Pineoblastoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pineoblastoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pineoblastoma.html#dataset-geo-gse180868"}],"context_names":["Pineoblastoma"],"disease_names":["Pineoblastoma"],"disease_name":"Pineoblastoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Pineoblastoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pineoblastoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Pineoblastoma.html#dataset-geo-gse180868"]},{"id":"dataset:geo:gse18152","accession":"geo:GSE18152","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE18152","title":"Screening for chromosomal aberrations by array CGH in 74 patients with congenital hypothyroidism","alternate_titles":[],"description":"Congenital Hypothyroidism occurs in 1:3500 live births and is therefore the most common congenital endocrine disorder. A spectrum of defective thyroid morphology, termed thyroid dysgenesis, represents 80% of permanent CH cases. Although several candidate genes have been implicated in thyroid development, comprehensive screens failed to detect mutation carriers in a significant number of patients with non-syndromic TD. Due to the sporadic occurrence of TD, de novo chromosomal rearrangements are conceivably representing one of the molecular mechanisms participating in its aetiology.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[80],"sample_count":80,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:20427504"],"publication_contexts":[{"context_id":"disorder:Congenital_Hypothyroidism","publication":"PMID:20427504"}],"publication":"PMID:20427504","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/20427504","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Congenital Hypothyroidism (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Congenital_Hypothyroidism","name":"Congenital Hypothyroidism","kind":"Disorder","source_path":"kb/disorders/Congenital_Hypothyroidism.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Congenital_Hypothyroidism.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Congenital_Hypothyroidism.html#dataset-geo-gse18152"}],"context_names":["Congenital Hypothyroidism"],"disease_names":["Congenital Hypothyroidism"],"disease_name":"Congenital Hypothyroidism","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Congenital_Hypothyroidism.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Congenital_Hypothyroidism.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Congenital_Hypothyroidism.html#dataset-geo-gse18152"]},{"id":"dataset:geo:gse181815","accession":"geo:GSE181815","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE181815","title":"Molecular predictors of response to pembrolizumab in thymic carcinoma","alternate_titles":[],"description":"Thymic carcinoma is rare and has a poorer prognosis than thymomas. The treatment options are limited after failure of platinum-based chemotherapy. We previously performed a single center phase II study of pembrolizumab in patients with advanced thymic carcinoma, showing a 22.5% response rate. Here, we characterized the genomic and transcriptomic profile of thymic carcinoma samples from 10 patients (5 non-responders vs 5 responders) in this cohort, with the main aim of identifying potential predictors of response to immunotherapy.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[30],"sample_count":30,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:34622229"],"publication_contexts":[{"context_id":"disorder:Thymic_Carcinoma","publication":"PMID:34622229"}],"publication":"PMID:34622229","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34622229","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Thymic Carcinoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Thymic_Carcinoma","name":"Thymic Carcinoma","kind":"Disorder","source_path":"kb/disorders/Thymic_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Thymic_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Thymic_Carcinoma.html#dataset-geo-gse181815"}],"context_names":["Thymic Carcinoma"],"disease_names":["Thymic Carcinoma"],"disease_name":"Thymic Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Thymic_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Thymic_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Thymic_Carcinoma.html#dataset-geo-gse181815"]},{"id":"dataset:geo:gse182038","accession":"geo:GSE182038","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE182038","title":"Elevated N-linked glycosylation of IgG variable regions in myasthenia gravis disease subtypes","alternate_titles":[],"description":"Elevated N-linked glycosylation of immunoglobulin G variable regions (IgG-VN-Glyc) is an emerging molecular phenotype associated with autoimmune disorders. To test the broader specificity of elevated IgG-VN-Glyc, we studied patients with distinct subtypes of myasthenia gravis (MG), a B cell-mediated autoimmune disease. Our experimental design included adaptive immune receptor repertoire sequencing to quantify and characterize N-glycosylation sites in the global B cell receptor repertoire, proteomics to examine glycosylation patterns of the circulating IgG, and production of human-derived recombinant autoantibodies, which were studied with mass spectrometry and antigen binding assays to confi...","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[31],"sample_count":31,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:34544801"],"publication_contexts":[{"context_id":"disorder:Myasthenia_Gravis","publication":"PMID:34544801"}],"publication":"PMID:34544801","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34544801","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Myasthenia Gravis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Myasthenia_Gravis","name":"Myasthenia Gravis","kind":"Disorder","source_path":"kb/disorders/Myasthenia_Gravis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myasthenia_Gravis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Myasthenia_Gravis.html#dataset-geo-gse182038"}],"context_names":["Myasthenia Gravis"],"disease_names":["Myasthenia Gravis"],"disease_name":"Myasthenia Gravis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Myasthenia_Gravis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myasthenia_Gravis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Myasthenia_Gravis.html#dataset-geo-gse182038"]},{"id":"dataset:geo:gse182740","accession":"geo:GSE182740","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE182740","title":"Genomic profiling of the overlap phenotype between psoriasis and atopic dermatitis","alternate_titles":[],"description":"Clinical overlaps between psoriasis and atopic dermatitis are sometimes undiscernible, and there is no consensus whether to treat the overlap phenotype as psoriasis or atopic dermatitis. We enrolled patients diagnosed with either psoriasis or atopic dermatitis, and clinically re-stratified them into classic psoriasis, classic atopic dermatitis, and the overlap phenotype between psoriasis and atopic dermatitis. We compared gene expression profiles of lesional and nonlesional skin biopsy tissues between the three comparison groups.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[75],"sample_count":75,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37419444"],"publication_contexts":[{"context_id":"disorder:Atopic_Dermatitis","publication":"PMID:37419444"}],"publication":"PMID:37419444","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37419444","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Atopic Dermatitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Atopic_Dermatitis","name":"Atopic Dermatitis","kind":"Disorder","source_path":"kb/disorders/Atopic_Dermatitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Atopic_Dermatitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Atopic_Dermatitis.html#dataset-geo-gse182740"}],"context_names":["Atopic Dermatitis"],"disease_names":["Atopic Dermatitis"],"disease_name":"Atopic Dermatitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Atopic_Dermatitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Atopic_Dermatitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Atopic_Dermatitis.html#dataset-geo-gse182740"]},{"id":"dataset:geo:gse183156","accession":"geo:GSE183156","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE183156","title":"Long-Term Hepatitis B Virus Infection Induces Cytopathic Effects in Primary Human Hepatocytes, and Can be Partially Reversed by Antiviral Therapy","alternate_titles":[],"description":"Based on our recently developed 5 chemicals-cultured primary human hepatocytes (5C-PHH) model that supports long-term HBV infection, we performed multiplexed quantitative analysis of temporal changes of host proteome and transcriptome on PHH cells infected by HBV for up to 4 weeks. We showed that metabolic-, complement-, cytoskeleton-, mitochondrial- and oxidation-related pathways were modulated at transcriptional or post-transcriptional levels during long-term HBV infection, which led to cytopathic effects and could be partially rescued by early rather than late nucleot(s)ide analogs (NAs) administration.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[24],"sample_count":24,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:35171034"],"publication_contexts":[{"context_id":"disorder:Hepatitis_B","publication":"PMID:35171034"}],"publication":"PMID:35171034","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35171034","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Hepatitis B (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Hepatitis_B","name":"Hepatitis B","kind":"Disorder","source_path":"kb/disorders/Hepatitis_B.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatitis_B.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hepatitis_B.html#dataset-geo-gse183156"}],"context_names":["Hepatitis B"],"disease_names":["Hepatitis B"],"disease_name":"Hepatitis B","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hepatitis_B.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatitis_B.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hepatitis_B.html#dataset-geo-gse183156"]},{"id":"dataset:geo:gse183281","accession":"geo:GSE183281","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE183281","title":"PAX3-FOXO1 coordinates enhancer architecture, eRNA transcription, and controls RNA polymerase pause release at select gene targets","alternate_titles":[],"description":"Most causally informative ARMS dataset available. Uses dTAG-mediated targeted degradation of endogenously tagged PAX3-FOXO1 in RH4 and RH30 cell lines with time-resolved multi-omics (0.5–72 h). ATAC-seq tracks chromatin accessibility loss in real time; PRO-seq captures nascent enhancer RNA transcription to identify active super-enhancer elements; CUT&RUN maps histone marks; RNA-seq defines direct vs. indirect gene expression responses. SuperSeries comprising 10 subseries (≥209 samples total). Definitively distinguishes immediate-early PAX3-FOXO1 direct targets from secondary transcriptional cascades.","alternate_descriptions":[],"data_types":["MULTI_OMICS_PERTURBATION"],"data_type_labels":["Multi Omics Perturbation"],"data_type_label":"Multi Omics Perturbation","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0001134","label":"skeletal muscle tissue","display_label":"skeletal muscle tissue","url":"http://purl.obolibrary.org/obo/UBERON_0001134"}],"sample_type_labels":["skeletal muscle tissue"],"sample_counts":[209],"sample_count":209,"conditions":["PAX3-FOXO1 dTAG degradation (0.5–72 h time course)","DMSO control"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["Illumina NovaSeq 6000"],"platform":"Illumina NovaSeq 6000","publications":["PMID:36395771"],"publication_contexts":[{"context_id":"disorder:Alveolar_Rhabdomyosarcoma","publication":"PMID:36395771"}],"publication":"PMID:36395771","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36395771","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:36395771","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/36395771","reference_title":"PAX3-FOXO1 coordinates enhancer architecture, eRNA transcription, and RNA polymerase pause release at select gene targets.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We used a chemical-genetic approach to rapidly degrade a canonical transcriptional activator, PAX3-FOXO1, to define the mechanism by which it regulates gene expression programs.","explanation":"Describes the rapid PAX3-FOXO1 degradation strategy that generated this time-resolved multi-omics dataset."}],"notes":["SuperSeries (GSE183281); 10 component subseries covering ATAC-seq, PRO-seq, ChIP-seq, CUT&RUN, and RNA-seq in RH4 and RH30 lines. The PRO-seq component is unique — capturing eRNA transcription at active super-enhancers provides the most direct readout of PAX3-FOXO1 SE activity available in any published ARMS dataset."],"contexts":[{"id":"disorder:Alveolar_Rhabdomyosarcoma","name":"Alveolar Rhabdomyosarcoma","kind":"Disorder","source_path":"kb/disorders/Alveolar_Rhabdomyosarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alveolar_Rhabdomyosarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Alveolar_Rhabdomyosarcoma.html#dataset-geo-gse183281"}],"context_names":["Alveolar Rhabdomyosarcoma"],"disease_names":["Alveolar Rhabdomyosarcoma"],"disease_name":"Alveolar Rhabdomyosarcoma","same_context_model_ids":["model:kb/disorders/Alveolar_Rhabdomyosarcoma.yaml:Fusion-positive RMS cancer-associated fibroblast coculture","model:kb/disorders/Alveolar_Rhabdomyosarcoma.yaml:Patient-derived ARMS single-cell culture model"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Alveolar_Rhabdomyosarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alveolar_Rhabdomyosarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Alveolar_Rhabdomyosarcoma.html#dataset-geo-gse183281"]},{"id":"dataset:geo:gse183346","accession":"geo:GSE183346","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE183346","title":"High throughput sequencing data of ovarian hyperstimulation syndrome (OHSS) mouse model","alternate_titles":[],"description":"RNA sequencing of ovaries from an established mouse OHSS model, reported as showing strengthened cell junctions between ovarian vessels after drug treatment - the transcriptional counterpart of the inter-endothelial junction loosening that this entry curates as the VEGFR-2-mediated permeability node.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"house mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:35221672"],"publication_contexts":[{"context_id":"disorder:Ovarian_Hyperstimulation_Syndrome","publication":"PMID:35221672"}],"publication":"PMID:35221672","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35221672","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search (scripts/discover_datasets.py) and verified against NCBI E-utilities on 2026-08-25; title, sample count and organism are GEO's own values. Relevance triaged manually: this is the OHSS syndrome itself in a disease model, not merely a superovulation protocol. Two other DIRECT-scored candidates were rejected on that same triage - GSE229048 (ovine caruncular endometrium after FSH superovulation) studies the uterus after a stimulation protocol rather than the hyperstimulation syndrome, and GSE39402 is an epithelial ovarian tumour model. Both would have resolved perfectly while being about something else."],"contexts":[{"id":"disorder:Ovarian_Hyperstimulation_Syndrome","name":"Ovarian Hyperstimulation Syndrome","kind":"Disorder","source_path":"kb/disorders/Ovarian_Hyperstimulation_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ovarian_Hyperstimulation_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Ovarian_Hyperstimulation_Syndrome.html#dataset-geo-gse183346"}],"context_names":["Ovarian Hyperstimulation Syndrome"],"disease_names":["Ovarian Hyperstimulation Syndrome"],"disease_name":"Ovarian Hyperstimulation Syndrome","same_context_model_ids":["model:kb/disorders/Ovarian_Hyperstimulation_Syndrome.yaml:SVOG human granulosa-lutein cell line with Tie1 silencing"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Ovarian_Hyperstimulation_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ovarian_Hyperstimulation_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Ovarian_Hyperstimulation_Syndrome.html#dataset-geo-gse183346"]},{"id":"dataset:geo:gse183716","accession":"geo:GSE183716","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE183716","title":"The innate and adaptive immune landscape of SARS-CoV-2-associated multisystem inflammatory syndrome in children (MIS-C) from acute disease to recovery","alternate_titles":[],"description":"Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening disease occurring several weeks after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Deep immune profiling showed acute MIS-C patients had highly activated neutrophils, classical monocytes and memory CD8+ T-cells; increased frequencies of B-cell plasmablasts and double-negative B-cells. Post treatment samples from the same patients, taken when symptoms were resolving, identified recovery-associated immune features including CD163+ monocytes, emergence of a new population of immature neutrophils and, in some patients, a transient increase in arginase.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[8],"sample_count":8,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:34632327"],"publication_contexts":[{"context_id":"disorder:Multisystem_Inflammatory_Syndrome_in_Children_MIS-C","publication":"PMID:34632327"}],"publication":"PMID:34632327","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34632327","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Multisystem Inflammatory Syndrome in Children (MIS-C) (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Multisystem_Inflammatory_Syndrome_in_Children_MIS-C","name":"Multisystem Inflammatory Syndrome in Children (MIS-C)","kind":"Disorder","source_path":"kb/disorders/Multisystem_Inflammatory_Syndrome_in_Children_MIS-C.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Multisystem_Inflammatory_Syndrome_in_Children_MIS-C.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Multisystem_Inflammatory_Syndrome_in_Children_MIS-C.html#dataset-geo-gse183716"}],"context_names":["Multisystem Inflammatory Syndrome in Children (MIS-C)"],"disease_names":["Multisystem Inflammatory Syndrome in Children (MIS-C)"],"disease_name":"Multisystem Inflammatory Syndrome in Children (MIS-C)","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Multisystem_Inflammatory_Syndrome_in_Children_MIS-C.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Multisystem_Inflammatory_Syndrome_in_Children_MIS-C.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Multisystem_Inflammatory_Syndrome_in_Children_MIS-C.html#dataset-geo-gse183716"]},{"id":"dataset:geo:gse184316","accession":"geo:GSE184316","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE184316","title":"Lung microenvironments and disease progression in fibrotic hypersensitivity pneumonitis","alternate_titles":[],"description":"Rationale: Fibrotic hypersensitivity pneumonitis (fHP) is an interstitial lung disease caused by sensitization to an inhaled allergen. Objectives: We aimed to identify the molecular determinants associated with progression of fibrosis. Methods: Nine fHP explant lungs and six unused donor lungs (as controls) were systematically sampled (4 samples/lung). According to microCT measures, fHP cores were clustered into a mild, moderate and severe fibrosis group. Gene expression profiles were assessed using Weighted Gene Co-expression Network Analysis (WGCNA), xCell, gene ontology and structure enrichment analysis. Gene expression of the prevailing molecular traits was also compared with IPF.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[100],"sample_count":100,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Hypersensitivity pneumonitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Hypersensitivity_Pneumonitis","name":"Hypersensitivity pneumonitis","kind":"Disorder","source_path":"kb/disorders/Hypersensitivity_Pneumonitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hypersensitivity_Pneumonitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hypersensitivity_pneumonitis.html#dataset-geo-gse184316"}],"context_names":["Hypersensitivity pneumonitis"],"disease_names":["Hypersensitivity pneumonitis"],"disease_name":"Hypersensitivity pneumonitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hypersensitivity_Pneumonitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hypersensitivity_Pneumonitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hypersensitivity_pneumonitis.html#dataset-geo-gse184316"]},{"id":"dataset:geo:gse184520","accession":"geo:GSE184520","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE184520","title":"Iron accumulation and changes of cellular organelles in WDR45 mutant fibroblasts","alternate_titles":[],"description":"Iron overload in the brain, defined as excess stores of iron, is known to be related to neurological disorder. Among neurodegeneration with brain iron accumulation, we reported a specific point mutation, 977-1G>A in WDR45, showing iron accumulation in the brain, and autophagy defects in the fibroblasts. In this study, we investigated whether fibroblasts with mutated WDR45 accumulated iron, and other effects on cellular organelles. We first identified the main location of iron accumulation in the mutant fibroblasts and then investigated the effects of this accumulation on other organelles, including lipid droplets, mitochondria, and lysosomes.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:34769084"],"publication_contexts":[{"context_id":"disorder:Neurodegeneration_With_Brain_Iron_Accumulation","publication":"PMID:34769084"}],"publication":"PMID:34769084","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34769084","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Neurodegeneration With Brain Iron Accumulation (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Neurodegeneration_With_Brain_Iron_Accumulation","name":"Neurodegeneration With Brain Iron Accumulation","kind":"Disorder","source_path":"kb/disorders/Neurodegeneration_With_Brain_Iron_Accumulation.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Neurodegeneration_With_Brain_Iron_Accumulation.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Neurodegeneration_With_Brain_Iron_Accumulation.html#dataset-geo-gse184520"}],"context_names":["Neurodegeneration With Brain Iron Accumulation"],"disease_names":["Neurodegeneration With Brain Iron Accumulation"],"disease_name":"Neurodegeneration With Brain Iron Accumulation","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Neurodegeneration_With_Brain_Iron_Accumulation.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Neurodegeneration_With_Brain_Iron_Accumulation.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Neurodegeneration_With_Brain_Iron_Accumulation.html#dataset-geo-gse184520"]},{"id":"dataset:geo:gse184898","accession":"geo:GSE184898","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE184898","title":"Transcriptome analysis of naive CD4T cells from Granulomatosis with Polyangiitis(GPA) patients and healthy control (HC)","alternate_titles":[],"description":"Analysis of transcriptional profile of GPA and HC naive CD4 T cells to understand intrinsic molecular differences after early TCR activation that may explain different effector T cell genereation.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[20],"sample_count":20,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:35039330"],"publication_contexts":[{"context_id":"disorder:Granulomatosis_with_Polyangiitis","publication":"PMID:35039330"}],"publication":"PMID:35039330","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35039330","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Granulomatosis with Polyangiitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Granulomatosis_with_Polyangiitis","name":"Granulomatosis with Polyangiitis","kind":"Disorder","source_path":"kb/disorders/Granulomatosis_with_Polyangiitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Granulomatosis_with_Polyangiitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Granulomatosis_with_Polyangiitis.html#dataset-geo-gse184898"}],"context_names":["Granulomatosis with Polyangiitis"],"disease_names":["Granulomatosis with Polyangiitis"],"disease_name":"Granulomatosis with Polyangiitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Granulomatosis_with_Polyangiitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Granulomatosis_with_Polyangiitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Granulomatosis_with_Polyangiitis.html#dataset-geo-gse184898"]},{"id":"dataset:geo:gse184906","accession":"geo:GSE184906","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE184906","title":"Autophagy and lysosomal dysfunction in Tay Sachs disease are restored by mTOR modulation","alternate_titles":[],"description":"Expression profiling associated with studies of autophagy, mTOR signaling and lysosomal integrity in Tay-Sachs/GM2 patient fibroblasts. Cellular findings and partial L-arginine rescue do not establish a neuronal or clinical therapeutic effect.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:34831346"],"publication_contexts":[{"context_id":"disorder:Tay-Sachs_Disease","publication":"PMID:34831346"}],"publication":"PMID:34831346","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34831346","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["GEO metadata verified on 2026-09-04; the 12 expression samples are not a clinical trial or a 12-patient efficacy cohort."],"contexts":[{"id":"disorder:Tay-Sachs_Disease","name":"Tay-Sachs Disease","kind":"Disorder","source_path":"kb/disorders/Tay-Sachs_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Tay-Sachs_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Tay-Sachs_Disease.html#dataset-geo-gse184906"}],"context_names":["Tay-Sachs Disease"],"disease_names":["Tay-Sachs Disease"],"disease_name":"Tay-Sachs Disease","same_context_model_ids":["model:kb/disorders/Tay-Sachs_Disease.yaml:GM2-loaded neuronal cultures","model:kb/disorders/Tay-Sachs_Disease.yaml:Patient-derived GM2 skin fibroblasts","model:kb/disorders/Tay-Sachs_Disease.yaml:Sandhoff cerebral organoids with isogenic correction"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Tay-Sachs_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Tay-Sachs_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Tay-Sachs_Disease.html#dataset-geo-gse184906"]},{"id":"dataset:geo:gse185041","accession":"geo:GSE185041","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE185041","title":"Genetic and epigenetic characterization of posterior pituitary tumors","alternate_titles":[],"description":"Pituicytoma (PITUI), granular cell tumor (GCT), and spindle cell oncocytoma (SCO) are rare tumors of the posterior pituitary lobe. Histologically, they may be challenging to distinguish and have been proposed to represent a histological spectrum of a single entity. We performed targeted next-generation sequencing, DNA methylation profiling, and copy number analysis on 47 tumors (14 PITUI; 12 GCT; 21 SCO) to investigate molecular features and explore possibilities of clinically meaningful tumor subclassification. We detected two main epigenomic subgroups by unsupervised clustering of DNA methylation data, though the overall methylation differences were subtle.","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[47],"sample_count":47,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:34661724"],"publication_contexts":[{"context_id":"disorder:Granular_Cell_Tumor","publication":"PMID:34661724"}],"publication":"PMID:34661724","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34661724","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Granular Cell Tumor (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Granular_Cell_Tumor","name":"Granular Cell Tumor","kind":"Disorder","source_path":"kb/disorders/Granular_Cell_Tumor.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Granular_Cell_Tumor.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Granular_Cell_Tumor.html#dataset-geo-gse185041"}],"context_names":["Granular Cell Tumor"],"disease_names":["Granular Cell Tumor"],"disease_name":"Granular Cell Tumor","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Granular_Cell_Tumor.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Granular_Cell_Tumor.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Granular_Cell_Tumor.html#dataset-geo-gse185041"]},{"id":"dataset:geo:gse185300","accession":"geo:GSE185300","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE185300","title":"Expression data from adult left ventricular heart tissue of hypereosinophilic mice and controls","alternate_titles":[],"description":"Microarray profiling of left ventricular myocardium from IL-5 transgenic hypereosinophilic mice against controls, the transcriptional dataset behind the tissue damage and remodeling signature cited for the cardiac injury node. Model-organism data: it addresses the eosinophil effector arm shared with idiopathic HES, not the unexplained driver specific to it.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"house mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37829205"],"publication_contexts":[{"context_id":"disorder:Idiopathic_Hypereosinophilic_Syndrome","publication":"PMID:37829205"}],"publication":"PMID:37829205","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37829205","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Selected after relevance triage of the GEO candidate list. Two higher-scoring DIRECT candidates were rejected: geo:GSE12079 profiles CD3-CD4+ T cells from the lymphocytic variant, which this entry excludes by definition, and geo:GSE131738 is Sezary syndrome. Every GENE_ONLY candidate matched on PDGFRA, which reaches this disease only through the MONDO term's erroneous OMIM-derived axiom."],"contexts":[{"id":"disorder:Idiopathic_Hypereosinophilic_Syndrome","name":"Idiopathic Hypereosinophilic Syndrome","kind":"Disorder","source_path":"kb/disorders/Idiopathic_Hypereosinophilic_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Idiopathic_Hypereosinophilic_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Idiopathic_Hypereosinophilic_Syndrome.html#dataset-geo-gse185300"}],"context_names":["Idiopathic Hypereosinophilic Syndrome"],"disease_names":["Idiopathic Hypereosinophilic Syndrome"],"disease_name":"Idiopathic Hypereosinophilic Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Idiopathic_Hypereosinophilic_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Idiopathic_Hypereosinophilic_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Idiopathic_Hypereosinophilic_Syndrome.html#dataset-geo-gse185300"]},{"id":"dataset:geo:gse185565","accession":"geo:GSE185565","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE185565","title":"NGS-based miRNome profile in cardiac muscle tissue of congenital heart disease patients","alternate_titles":[],"description":"Small-RNA sequencing of human cardiac tissue across atrial septal defect, ventricular septal defect, tetralogy of Fallot, and non-CHD controls. The dataset is useful for exploratory miRNA comparisons but is not an ASD-specific or adequately powered causal cohort.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0001133","label":"cardiac muscle tissue","display_label":"cardiac muscle tissue","url":"http://purl.obolibrary.org/obo/UBERON_0001133"}],"sample_type_labels":["cardiac muscle tissue"],"sample_counts":[10],"sample_count":10,"conditions":["atrial septal defect","ventricular septal defect","tetralogy of Fallot","non-congenital-heart-disease control"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"url:https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE185565","reference_url":null,"reference_title":"GEO Accession viewer","supports":"SUPPORT","evidence_source":"OTHER","snippet":"The goal of this study was to explore the miRNome profile in three frequently occurring Congenital Heart Disease (CHD) types, namely Atrial Septal Defect (ASD), Ventricular Septal Defect (VSD) and Tetralogy of Fallot (TOF).","explanation":"The official GEO series record directly documents ASD among the cardiac tissue miRNA cohorts represented by GSE185565."}],"notes":["GEO metadata list two ASD samples, two non-CHD controls, four VSD samples, and two tetralogy-of-Fallot samples; ASD-specific inference is therefore severely sample-limited."],"contexts":[{"id":"disorder:Atrial_Septal_Defect","name":"Atrial Septal Defect","kind":"Disorder","source_path":"kb/disorders/Atrial_Septal_Defect.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Atrial_Septal_Defect.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Atrial_Septal_Defect.html#dataset-geo-gse185565"}],"context_names":["Atrial Septal Defect"],"disease_names":["Atrial Septal Defect"],"disease_name":"Atrial Septal Defect","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Atrial_Septal_Defect.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Atrial_Septal_Defect.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Atrial_Septal_Defect.html#dataset-geo-gse185565"]},{"id":"dataset:geo:gse186334","accession":"geo:GSE186334","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE186334","title":"Compartment-specific total RNA profile of Hippocampal and Cortical cells from Mesial Temporal Lobe Epilepsy tissue","alternate_titles":[],"description":"Mesial temporal lobe epilepsy (mTLE) is a chronic neurological disease characterized by recurrent seizures. The pathogenic mechanisms underlying TLE involve defects in post-transcriptional regulation of gene expression. So far, transcriptome profiles from epileptic tissue have been performed using whole cells, thereby lacking information on RNA localization and function at a subcellular level. In this project, we set out to understand the compartment-specific total RNA profile of human mTLE tissue samples. For this, we had established a protocol to isolate cytoplasmic and nuclear compartments from human hippocampal tissue.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[68],"sample_count":68,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:35310884"],"publication_contexts":[{"context_id":"disorder:Mesial_Temporal_Lobe_Epilepsy_with_Hippocampal_Sclerosis","publication":"PMID:35310884"}],"publication":"PMID:35310884","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35310884","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Mesial_Temporal_Lobe_Epilepsy_with_Hippocampal_Sclerosis","name":"Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis","kind":"Disorder","source_path":"kb/disorders/Mesial_Temporal_Lobe_Epilepsy_with_Hippocampal_Sclerosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mesial_Temporal_Lobe_Epilepsy_with_Hippocampal_Sclerosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Mesial_Temporal_Lobe_Epilepsy_with_Hippocampal_Sclerosis.html#dataset-geo-gse186334"}],"context_names":["Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis"],"disease_names":["Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis"],"disease_name":"Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Mesial_Temporal_Lobe_Epilepsy_with_Hippocampal_Sclerosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mesial_Temporal_Lobe_Epilepsy_with_Hippocampal_Sclerosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Mesial_Temporal_Lobe_Epilepsy_with_Hippocampal_Sclerosis.html#dataset-geo-gse186334"]},{"id":"dataset:geo:gse186408","accession":"geo:GSE186408","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE186408","title":"Novel transcriptional and translational biomarkers of tularemia vaccine efficacy in a mouse inhalation model: proof of concept","alternate_titles":[],"description":"Francisella tularensis subspecies tularensis (Ftt) is extremely virulent for humans when inhaled as small particle aerosols (<5μm). Inhalation of ≥ 20 viable bacteria is sufficient to initiate infection with a mortality rate ≥30%. Consequently, in the past, Ftt became a primary candidate for biological weapons development. To counter this threat, the USA developed a live vaccine strain that showed efficacy in humans against inhalation of virulent Ftt. However, the breakthrough dose was fairly low and protection waned with time. These weaknesses triggered extensive research for better vaccine candidates.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[20],"sample_count":20,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Tularemia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Tularemia","name":"Tularemia","kind":"Disorder","source_path":"kb/disorders/Tularemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Tularemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Tularemia.html#dataset-geo-gse186408"}],"context_names":["Tularemia"],"disease_names":["Tularemia"],"disease_name":"Tularemia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Tularemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Tularemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Tularemia.html#dataset-geo-gse186408"]},{"id":"dataset:geo:gse186564","accession":"geo:GSE186564","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE186564","title":"Human microRNA-122b-5p regulates chikungunya virus replication in macrophages by directly targeting viral 3'-UTR and cellular histone deacetylase 4","alternate_titles":[],"description":"We found that Histone Deacetylase 4 is the target of human miR-122b-5p using transcriptome approach and report that HDAC4 is downregulated in CHIKV infected human macrophages through global transcriptome profiling","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[18],"sample_count":18,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40956096"],"publication_contexts":[{"context_id":"disorder:Chikungunya","publication":"PMID:40956096"}],"publication":"PMID:40956096","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40956096","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Chikungunya (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Chikungunya","name":"Chikungunya","kind":"Disorder","source_path":"kb/disorders/Chikungunya.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chikungunya.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chikungunya.html#dataset-geo-gse186564"}],"context_names":["Chikungunya"],"disease_names":["Chikungunya"],"disease_name":"Chikungunya","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chikungunya.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chikungunya.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chikungunya.html#dataset-geo-gse186564"]},{"id":"dataset:geo:gse186593","accession":"geo:GSE186593","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE186593","title":"Comprehensive expression profiles of mRNAs, lncRNAs and miRNAs in Kashin-Beck Disease identified by RNA-sequencing","alternate_titles":[],"description":"mRNA, lncRNA and miRNA expression profiles from Kashin-Beck disease cartilage.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:34913457"],"publication_contexts":[{"context_id":"disorder:Kashin-Beck_Disease","publication":"PMID:34913457"}],"publication":"PMID:34913457","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34913457","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE186593","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE186593","reference_title":"Comprehensive expression profiles of mRNAs, lncRNAs and miRNAs in Kashin-Beck Disease identified by RNA-sequencing","supports":"SUPPORT","evidence_source":"OTHER","snippet":"RNA‐seq technology to detect the differentially expressed mRNAs, lncRNAs and miRNAs in KBD patients.","explanation":"The assay and the three RNA classes profiled, from GEO's own summary. Graded OTHER as a repository record rather than a study result."}],"notes":[],"contexts":[{"id":"disorder:Kashin-Beck_Disease","name":"Kashin-Beck Disease","kind":"Disorder","source_path":"kb/disorders/Kashin-Beck_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Kashin-Beck_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Kashin-Beck_Disease.html#dataset-geo-gse186593"}],"context_names":["Kashin-Beck Disease"],"disease_names":["Kashin-Beck Disease"],"disease_name":"Kashin-Beck Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Kashin-Beck_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Kashin-Beck_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Kashin-Beck_Disease.html#dataset-geo-gse186593"]},{"id":"dataset:geo:gse186789","accession":"geo:GSE186789","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE186789","title":"ASPSCR1-TFE3 orchestrates the angiogenic program of alveolar soft part sarcoma I","alternate_titles":[],"description":"Alveolar soft part sarcoma (ASPS) is a rare soft part malignancy affecting adolescents and young adult. ASPS is characterized by its alveolar structure consisting of tumor cells and highly integrated vascular network, and its high metastatic potential indicates the importance of the prominent angiogenic activity of ASPS. Here we find that the expression of ASPSCR1-TFE3, the fusion transcription factor causatively associated with ASPS, is dispensable for in vitro tumor maintenance but required for in vivo tumor development via angiogenesis.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[27],"sample_count":27,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37029109"],"publication_contexts":[{"context_id":"disorder:Alveolar_Soft_Part_Sarcoma","publication":"PMID:37029109"}],"publication":"PMID:37029109","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37029109","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Alveolar Soft Part Sarcoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Alveolar_Soft_Part_Sarcoma","name":"Alveolar Soft Part Sarcoma","kind":"Disorder","source_path":"kb/disorders/Alveolar_Soft_Part_Sarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alveolar_Soft_Part_Sarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Alveolar_Soft_Part_Sarcoma.html#dataset-geo-gse186789"}],"context_names":["Alveolar Soft Part Sarcoma"],"disease_names":["Alveolar Soft Part Sarcoma"],"disease_name":"Alveolar Soft Part Sarcoma","same_context_model_ids":["model:kb/disorders/Alveolar_Soft_Part_Sarcoma.yaml:ASPSCR1-TFE3-Positive ASPS Tumor Cell Lines"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Alveolar_Soft_Part_Sarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alveolar_Soft_Part_Sarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Alveolar_Soft_Part_Sarcoma.html#dataset-geo-gse186789"]},{"id":"dataset:geo:gse186921","accession":"geo:GSE186921","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE186921","title":"A cerebrospinal fluid microRNA analysis of progressive supranuclear palsy.","alternate_titles":[],"description":"The cerebrospinal fluid miRNAs expression was markedly altered in the patients with progressive supranuclear palsy and controls.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[19],"sample_count":19,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:35039873"],"publication_contexts":[{"context_id":"disorder:Progressive_Supranuclear_Palsy","publication":"PMID:35039873"}],"publication":"PMID:35039873","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35039873","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Progressive Supranuclear Palsy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Progressive_Supranuclear_Palsy","name":"Progressive Supranuclear Palsy","kind":"Disorder","source_path":"kb/disorders/Progressive_Supranuclear_Palsy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Progressive_Supranuclear_Palsy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Progressive_Supranuclear_Palsy.html#dataset-geo-gse186921"}],"context_names":["Progressive Supranuclear Palsy"],"disease_names":["Progressive Supranuclear Palsy"],"disease_name":"Progressive Supranuclear Palsy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Progressive_Supranuclear_Palsy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Progressive_Supranuclear_Palsy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Progressive_Supranuclear_Palsy.html#dataset-geo-gse186921"]},{"id":"dataset:geo:gse186998","accession":"geo:GSE186998","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE186998","title":"Endothelial GNAQ p.R183Q activates phospholipase-Cbeta3, increases angiopoietin-2 and drives formation of enlarged blood vessels","alternate_titles":[],"description":"Introduction: Capillary malformation (CM) occurs sporadically and is associated with Sturge-Weber syndrome (SWS). The somatic mosaic mutation in GNAQ (c.548GàA, p.R183Q) is enriched in endothelial cells (EC) in skin CM and SWS brain CM. Our goal was to investigate how the mutant G-protein a-q subunit (Gaq) alters EC signaling and disrupts capillary morphogenesis. Approach and results: We used lentiviral constructs to express p.R183Q or wild-type GNAQ in normal human endothelial colony forming cells (EC-R183Q and EC-WT respectively). EC-R183Q constitutively activated phospholipase-C β3 (PLCβ3), a downstream effector of Gαq. Activated PLCβ3 was also detected in human CM tissue sections.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:34670408"],"publication_contexts":[{"context_id":"disorder:Sturge-Weber_Syndrome","publication":"PMID:34670408"}],"publication":"PMID:34670408","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34670408","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Sturge-Weber Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Sturge-Weber_Syndrome","name":"Sturge-Weber Syndrome","kind":"Disorder","source_path":"kb/disorders/Sturge-Weber_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sturge-Weber_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Sturge-Weber_Syndrome.html#dataset-geo-gse186998"}],"context_names":["Sturge-Weber Syndrome"],"disease_names":["Sturge-Weber Syndrome"],"disease_name":"Sturge-Weber Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Sturge-Weber_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sturge-Weber_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Sturge-Weber_Syndrome.html#dataset-geo-gse186998"]},{"id":"dataset:geo:gse187493","accession":"geo:GSE187493","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE187493","title":"Transcriptome analysis of skeletal muscle tissue from Hras G12V mutant mice","alternate_titles":[],"description":"Mouse bulk RNA-seq dataset profiling skeletal muscle from an activating Hras Costello syndrome model to define transcriptional programs associated with myopathy, hypotonia, and MAPK-driven rescue biology.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"house mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[{"id":"UBERON:0001134","label":"skeletal muscle tissue","display_label":"skeletal muscle tissue","url":"http://purl.obolibrary.org/obo/UBERON_0001134"}],"sample_type_labels":["skeletal muscle tissue"],"sample_counts":[6],"sample_count":6,"conditions":["HrasG12V Costello syndrome mouse model","wild-type skeletal muscle control"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:34553752"],"publication_contexts":[{"context_id":"disorder:Costello_Syndrome","publication":"PMID:34553752"}],"publication":"PMID:34553752","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34553752","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:34553752","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/34553752","reference_title":"MEK-inhibitor-mediated rescue of skeletal myopathy caused by activating Hras mutation in a Costello syndrome mouse model.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"To gain a better understanding of the mechanisms underlying hypotonia in CS, a mouse model with an activating HrasG12V allele was utilized.","explanation":"This study anchors the linked GEO RNA-seq dataset as a mechanistically relevant model-organism resource for Costello syndrome muscle pathology."}],"notes":[],"contexts":[{"id":"disorder:Costello_Syndrome","name":"Costello Syndrome","kind":"Disorder","source_path":"kb/disorders/Costello_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Costello_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Costello_Syndrome.html#dataset-geo-gse187493"}],"context_names":["Costello Syndrome"],"disease_names":["Costello Syndrome"],"disease_name":"Costello Syndrome","same_context_model_ids":["model:kb/disorders/Costello_Syndrome.yaml:Costello syndrome atrial-like cardiomyocyte model","model:kb/disorders/Costello_Syndrome.yaml:Costello syndrome patient fibroblast models"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Costello_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Costello_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Costello_Syndrome.html#dataset-geo-gse187493"]},{"id":"dataset:geo:gse188202","accession":"geo:GSE188202","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE188202","title":"Transcriptional evaluation of the ductus arteriosus at the single cell level uncovers a requirement for vimentin for complete closure","alternate_titles":[],"description":"Failure to close the ductus arteriosus immediately post-birth, patent ductus arteriosus (PDA), accounts for up to 10% of all congenital heart defects. Despite significant advances in PDA management options, including pharmacological treatment targeting the prostaglandin pathway, a proportion of patients fail to respond and must undergo surgical intervention. Thus, further refinement of the cellular and molecular mechanisms that govern vascular remodeling of this vessel is required.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:35443793"],"publication_contexts":[{"context_id":"disorder:Patent_Ductus_Arteriosus","publication":"PMID:35443793"}],"publication":"PMID:35443793","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35443793","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Patent Ductus Arteriosus (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Patent_Ductus_Arteriosus","name":"Patent Ductus Arteriosus","kind":"Disorder","source_path":"kb/disorders/Patent_Ductus_Arteriosus.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Patent_Ductus_Arteriosus.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Patent_Ductus_Arteriosus.html#dataset-geo-gse188202"}],"context_names":["Patent Ductus Arteriosus"],"disease_names":["Patent Ductus Arteriosus"],"disease_name":"Patent Ductus Arteriosus","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Patent_Ductus_Arteriosus.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Patent_Ductus_Arteriosus.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Patent_Ductus_Arteriosus.html#dataset-geo-gse188202"]},{"id":"dataset:geo:gse188238","accession":"geo:GSE188238","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE188238","title":"Cell cycle defects underlie childhood-onset cardiomyopathy associated with Noonan syndrome","alternate_titles":[],"description":"Bulk transcriptomic dataset integrating left ventricular myocardial tissue and patient-derived PTPN11N308S/+ iPSC-cardiomyocyte modeling to define mechanisms of Noonan syndrome-associated childhood cardiomyopathy.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[11],"sample_count":11,"conditions":["Noonan syndrome-associated cardiomyopathy","sarcomeric hypertrophic cardiomyopathy comparator","non-diseased cardiac control"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["GPL20301"],"platform":"GPL20301","publications":["PMID:34988410"],"publication_contexts":[{"context_id":"disorder:Noonan_Syndrome","publication":"PMID:34988410"}],"publication":"PMID:34988410","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34988410","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE188238","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE188238","reference_title":"Cell cycle defects underlie childhood-onset cardiomyopathy associated with Noonan syndrome","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"gene expression in left ventricular myocardial tissue from NS-CM, HCM and normal hearts","explanation":"Supports human myocardial tissue evidence for transcriptomic distinctions between Noonan cardiomyopathy and sarcomeric HCM."},{"reference":"GEO:GSE188238","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE188238","reference_title":"Cell cycle defects underlie childhood-onset cardiomyopathy associated with Noonan syndrome","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"complemented with disease modeling in cardiomyocytes differentiated from patient-derived PTPN11N308S/+ induced pluripotent stem cells","explanation":"Supports complementary in vitro iPSC-cardiomyocyte modeling of Noonan cardiomyopathy mechanisms."}],"notes":[],"contexts":[{"id":"disorder:Noonan_Syndrome","name":"Noonan Syndrome","kind":"Disorder","source_path":"kb/disorders/Noonan_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Noonan_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Noonan_Syndrome.html#dataset-geo-gse188238"}],"context_names":["Noonan Syndrome"],"disease_names":["Noonan Syndrome"],"disease_name":"Noonan Syndrome","same_context_model_ids":["model:kb/disorders/Noonan_Syndrome.yaml:Noonan syndrome cortical organoid model","model:kb/disorders/Noonan_Syndrome.yaml:Noonan syndrome iPSC-cardiomyocyte model"],"candidate_model_ids":["model:kb/disorders/Noonan_Syndrome.yaml:Noonan syndrome iPSC-cardiomyocyte model"],"association_basis":"Same publication as a NAM (candidate)","nam_disease_context":"Same publication as a NAM (candidate)","source_paths":["kb/disorders/Noonan_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Noonan_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Noonan_Syndrome.html#dataset-geo-gse188238"]},{"id":"dataset:geo:gse188514","accession":"geo:GSE188514","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE188514","title":"The N-terminal Region of Middle East Respiratory Syndrome Coronavirus Accessory Protein 8b is Essential for Enhanced Virulence of an Attenuated Murine Coronavirus","alternate_titles":[],"description":"Middle East respiratory syndrome coronavirus (MERS-CoV) is a beta coronavirus that emerged in 2012, causing severe pneumonia and renal failure. MERS-CoV encodes five accessory proteins. Some of them have been shown to interfere with host antiviral immune response. However, the roles of protein 8b in innate immunity and viral virulence was rarely studied. Here, we introduced individual MERS-CoV accessory protein genes into the genome of an attenuated murine coronavirus (Mouse hepatitis virus, MHV), respectively and found accessory protein 8b could enhance viral replication in vivo and in vitro, and increase the lethality of infected mice.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[10],"sample_count":10,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:34817197"],"publication_contexts":[{"context_id":"disorder:Middle_East_Respiratory_Syndrome","publication":"PMID:34817197"}],"publication":"PMID:34817197","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34817197","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Middle East Respiratory Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Middle_East_Respiratory_Syndrome","name":"Middle East Respiratory Syndrome","kind":"Disorder","source_path":"kb/disorders/Middle_East_Respiratory_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Middle_East_Respiratory_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Middle_East_Respiratory_Syndrome.html#dataset-geo-gse188514"}],"context_names":["Middle East Respiratory Syndrome"],"disease_names":["Middle East Respiratory Syndrome"],"disease_name":"Middle East Respiratory Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Middle_East_Respiratory_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Middle_East_Respiratory_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Middle_East_Respiratory_Syndrome.html#dataset-geo-gse188514"]},{"id":"dataset:geo:gse188555","accession":"geo:GSE188555","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE188555","title":"CLINICOPATHOLOGIC AND MOLECULAR ANALYSIS OF A BCOR-CCNB3+ UNDIFFERENTIATED SARCOMA OF THE KIDNEY REVEALS SIGNIFICANT EPI-GENETIC ALTERATION","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["MULTI_OMICS"],"data_type_labels":["Multi Omics"],"data_type_label":"Multi Omics","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:34819304"],"publication_contexts":[{"context_id":"disorder:Kidney_Sarcoma","publication":"PMID:34819304"}],"publication":"PMID:34819304","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34819304","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["A SuperSeries combining mutation, expression, DNA methylation and miRNA profiling of a single BCOR-CCNB3 fusion undifferentiated sarcoma arising in the kidney. Relevance was checked rather than assumed: this is a primary renal mesenchymal malignancy and so falls under this root entry, though the histiotype is not one of the six modeled in has_subtypes. It is a single case, so it describes one tumour rather than the class. Candidates scoring higher on name match in the same search were rejected on relevance - they profile clear cell sarcoma of the kidney and rhabdoid tumour of the kidney, both of which this entry explicitly excludes."],"contexts":[{"id":"disorder:Kidney_Sarcoma","name":"Kidney Sarcoma","kind":"Disorder","source_path":"kb/disorders/Kidney_Sarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Kidney_Sarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Kidney_Sarcoma.html#dataset-geo-gse188555"}],"context_names":["Kidney Sarcoma"],"disease_names":["Kidney Sarcoma"],"disease_name":"Kidney Sarcoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Kidney_Sarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Kidney_Sarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Kidney_Sarcoma.html#dataset-geo-gse188555"]},{"id":"dataset:geo:gse188793","accession":"geo:GSE188793","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE188793","title":"Microgravity on the International Space Station promotes survival and proliferation of human stem cell cardiomyocytes","alternate_titles":[],"description":"RNA sequencing from 3D hiPSC-derived cardiac progenitors cultured 3 weeks on the ISS. Microgravity cultures showed 3-fold larger sphere sizes, 20-fold higher nuclei counts, and upregulation of proliferation and contraction-associated genes. Demonstrates microgravity effects on cardiomyocyte growth and differentiation pathways relevant to cardiac hypertrophy.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0000948","label":"heart","display_label":"heart","url":"http://purl.obolibrary.org/obo/UBERON_0000948"}],"sample_type_labels":["heart"],"sample_counts":[],"sample_count":null,"conditions":["spaceflight microgravity","1G control on ISS"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:36084640"],"publication_contexts":[{"context_id":"disorder:Hypertrophic_Cardiomyopathy","publication":"PMID:36084640"}],"publication":"PMID:36084640","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36084640","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:36084640","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/36084640","reference_title":"Space microgravity improves proliferation of human iPSC-derived cardiomyocytes.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Compared with 1G cultures, the microgravity cultures had 3-fold larger sphere sizes, 20-fold higher counts of nuclei, and increased expression of proliferation markers. Highly enriched cardiomyocytes generated in space microgravity showed improved Ca2+ handling and increased expression of contraction-associated genes.","explanation":"Microgravity-induced cardiomyocyte proliferation and hypertrophic growth parallels pathological cardiomyocyte growth in HCM. The upregulation of proliferation and contraction genes in space provides a model for studying hypertrophic signaling pathways."}],"notes":[],"contexts":[{"id":"disorder:Hypertrophic_Cardiomyopathy","name":"Hypertrophic Cardiomyopathy","kind":"Disorder","source_path":"kb/disorders/Hypertrophic_Cardiomyopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hypertrophic_Cardiomyopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy.html#dataset-geo-gse188793"}],"context_names":["Hypertrophic Cardiomyopathy"],"disease_names":["Hypertrophic Cardiomyopathy"],"disease_name":"Hypertrophic Cardiomyopathy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hypertrophic_Cardiomyopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hypertrophic_Cardiomyopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy.html#dataset-geo-gse188793"]},{"id":"dataset:geo:gse189420","accession":"geo:GSE189420","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE189420","title":"TRIM71R595H/R595H mutations and TRIM71-KO in mESC lead to similar transcriptomic changes, which indicate a poised state toward neural differentiation","alternate_titles":[],"description":"Transcriptomic consequences of TRIM71 hypomorphic and null alleles in mouse embryonic stem cells. TRIM71 is one of the neural-stem-cell-fate genes curated on the dysgenesis hypothesis arm of this entry.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"house mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[20],"sample_count":20,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:32669","label":"TRIM71","display_label":"TRIM71","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/32669"}],"genes":["TRIM71"],"platforms":[],"platform":null,"publications":["PMID:35379995"],"publication_contexts":[{"context_id":"disorder:Congenital_Hydrocephalus","publication":"PMID:35379995"}],"publication":"PMID:35379995","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35379995","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Discovered with just discover-datasets (DIRECT, name match) and resolved with just verify-datasets. Relevance triaged manually: TRIM71 is curated in this entry's genetic section, so this is a gene-and-mechanism match rather than a gene-symbol-only hit."],"contexts":[{"id":"disorder:Congenital_Hydrocephalus","name":"Congenital Hydrocephalus","kind":"Disorder","source_path":"kb/disorders/Congenital_Hydrocephalus.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Congenital_Hydrocephalus.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Congenital_Hydrocephalus.html#dataset-geo-gse189420"}],"context_names":["Congenital Hydrocephalus"],"disease_names":["Congenital Hydrocephalus"],"disease_name":"Congenital Hydrocephalus","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Congenital_Hydrocephalus.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Congenital_Hydrocephalus.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Congenital_Hydrocephalus.html#dataset-geo-gse189420"]},{"id":"dataset:geo:gse189782","accession":"geo:GSE189782","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE189782","title":"A single cell transcriptional roadmap of human pacemaker cell differentiation","alternate_titles":[],"description":"Single-cell RNA sequencing and trajectory inference over human induced pluripotent stem cells differentiating into sinoatrial-node-like cardiomyocytes, resolving the head, tail and transitional subtypes and the WNT and TGF-beta signalling decisions that separate them. It is the developmental counterpart of the atlas above and the transcriptional map of the platform used by the hiPSC pacemaker-cardiomyocyte model in this entry.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:36217819"],"publication_contexts":[{"context_id":"disorder:Sick_Sinus_Syndrome_2_Autosomal_Dominant","publication":"PMID:36217819"}],"publication":"PMID:36217819","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36217819","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:36217819","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/36217819","reference_title":"A single cell transcriptional roadmap of human pacemaker cell differentiation.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Here, we performed single cell RNA sequencing (scRNA-seq) and trajectory inference on human induced pluripotent stem cells (hiPSCs) differentiating to SAN-like cardiomyocytes (SANCMs) to construct a roadmap of transcriptional changes and lineage decisions.","explanation":"Describes the assay and material behind this accession and ties it to the hiPSC pacemaker-cardiomyocyte platform recorded under experimental_models."}],"notes":["Wild-type differentiation series, no disease genotypes. Verified with just verify-datasets."],"contexts":[{"id":"disorder:Sick_Sinus_Syndrome_2_Autosomal_Dominant","name":"Sick Sinus Syndrome 2, Autosomal Dominant","kind":"Disorder","source_path":"kb/disorders/Sick_Sinus_Syndrome_2_Autosomal_Dominant.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sick_Sinus_Syndrome_2_Autosomal_Dominant.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Sick_Sinus_Syndrome_2,_Autosomal_Dominant.html#dataset-geo-gse189782"}],"context_names":["Sick Sinus Syndrome 2, Autosomal Dominant"],"disease_names":["Sick Sinus Syndrome 2, Autosomal Dominant"],"disease_name":"Sick Sinus Syndrome 2, Autosomal Dominant","same_context_model_ids":["model:kb/disorders/Sick_Sinus_Syndrome_2_Autosomal_Dominant.yaml:hiPSC-derived pacemaker cardiomyocytes as a human I_f measurement platform","model:kb/disorders/Sick_Sinus_Syndrome_2_Autosomal_Dominant.yaml:Patient-derived hiPSC lines carrying a heterozygous and a homozygous HCN4 variant (UKMi009-A, UKMi011-A)"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Sick_Sinus_Syndrome_2_Autosomal_Dominant.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sick_Sinus_Syndrome_2_Autosomal_Dominant.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Sick_Sinus_Syndrome_2,_Autosomal_Dominant.html#dataset-geo-gse189782"]},{"id":"dataset:geo:gse190335","accession":"geo:GSE190335","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE190335","title":"Expression data for Sweet Syndrome patient and Healthy Controls","alternate_titles":[],"description":"Acute febrile neutrophilic dermatosis (Sweet syndrome) is a potentially fatal multiorgan inflammatory disease characterized by fever, leukocytosis, and rash with a neutrophilic infiltrate. Disease pathophysiology remains elusive. Corticosteroids and steroid sparing agents remain mainstays of treatment, but refractory cases pose a clinical challenge. Transcriptomic profiling of a refractory Sweet syndrome patient will improve our understanding of pathophysiology of the disease and, ultimately wiil help us to find a guided therapy.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[23],"sample_count":23,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:36355435"],"publication_contexts":[{"context_id":"disorder:Sweet_Syndrome","publication":"PMID:36355435"}],"publication":"PMID:36355435","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36355435","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Sweet Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Sweet_Syndrome","name":"Sweet Syndrome","kind":"Disorder","source_path":"kb/disorders/Sweet_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sweet_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Sweet_Syndrome.html#dataset-geo-gse190335"}],"context_names":["Sweet Syndrome"],"disease_names":["Sweet Syndrome"],"disease_name":"Sweet Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Sweet_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sweet_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Sweet_Syndrome.html#dataset-geo-gse190335"]},{"id":"dataset:geo:gse190348","accession":"geo:GSE190348","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE190348","title":"Dementia with Lewy bodies post-mortem brains reveal differentially methylated CpG sites with biomarker potential","alternate_titles":[],"description":"Dementia with Lewy bodies (DLB) is a common form of dementia with known genetic and environmental interactions. However, the underlying epigenetic mechanisms which reflect these gene-environment interactions are poorly studied. Herein, we measured genome-wide DNA methylation profiles of post-mortem brain tissue (Broadmann area 7) from 15 pathologically confirmed DLB brains and compared them with 16 cognitively normal controls using Illumina MethylationEPIC arrays. We identified 17 significantly differentially methylated CpGs (DMCs) and 17 differentially methylated regions (DMRs) between the groups. The DMCs are mainly located at the CpG islands, promoter and first exon regions.","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[31],"sample_count":31,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:36418427"],"publication_contexts":[{"context_id":"disorder:Dementia_with_Lewy_Bodies","publication":"PMID:36418427"}],"publication":"PMID:36418427","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36418427","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Dementia with Lewy Bodies (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Dementia_with_Lewy_Bodies","name":"Dementia with Lewy Bodies","kind":"Disorder","source_path":"kb/disorders/Dementia_with_Lewy_Bodies.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dementia_with_Lewy_Bodies.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Dementia_with_Lewy_Bodies.html#dataset-geo-gse190348"}],"context_names":["Dementia with Lewy Bodies"],"disease_names":["Dementia with Lewy Bodies"],"disease_name":"Dementia with Lewy Bodies","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Dementia_with_Lewy_Bodies.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dementia_with_Lewy_Bodies.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Dementia_with_Lewy_Bodies.html#dataset-geo-gse190348"]},{"id":"dataset:geo:gse190620","accession":"geo:GSE190620","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE190620","title":"The application of second-generation sequencing in congenital pulmonary airway malformations","alternate_titles":[],"description":"Objective: To investigate the differential expression of genes in whole transcripts of congenital pulmonary airway malformation (CPAM) using second-generation sequencing (also known as next-generation sequencing, NGS) technology. Methods: Children with CPAM were strictly screened after setting the criteria, and grouped by taking CPAM parietal tissue and CPAM lesion tissue respectively, and RNA-Seq libraries were established separately using second-generation sequencing technology, followed by differential expression analysis and GO (gene ontology) functional enrichment analysis, KEGG pathway analysis and GSEA (Gene Set Enrichment Analysis) analysis.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[9],"sample_count":9,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:36443638"],"publication_contexts":[{"context_id":"disorder:Congenital_Pulmonary_Airway_Malformation","publication":"PMID:36443638"}],"publication":"PMID:36443638","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36443638","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Congenital Pulmonary Airway Malformation (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Congenital_Pulmonary_Airway_Malformation","name":"Congenital Pulmonary Airway Malformation","kind":"Disorder","source_path":"kb/disorders/Congenital_Pulmonary_Airway_Malformation.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Congenital_Pulmonary_Airway_Malformation.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Congenital_Pulmonary_Airway_Malformation.html#dataset-geo-gse190620"}],"context_names":["Congenital Pulmonary Airway Malformation"],"disease_names":["Congenital Pulmonary Airway Malformation"],"disease_name":"Congenital Pulmonary Airway Malformation","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Congenital_Pulmonary_Airway_Malformation.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Congenital_Pulmonary_Airway_Malformation.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Congenital_Pulmonary_Airway_Malformation.html#dataset-geo-gse190620"]},{"id":"dataset:geo:gse190760","accession":"geo:GSE190760","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE190760","title":"Single-Cell RNA sequencing reveals prophylactic Prednisone blunts cellular immunity in hemophilia B gene therapy","alternate_titles":[],"description":"Blood single-cell RNA sequencing from seven BBM-H901 gene-therapy participants at four time points (28 longitudinal samples). The study relates immune-cell profiles and prednisone exposure to FIX response. These are repeated blood samples, not 28 independent patients or patient joint tissue.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[28],"sample_count":28,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:35598604"],"publication_contexts":[{"context_id":"disorder:Hemophilia_B","publication":"PMID:35598604"}],"publication":"PMID:35598604","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35598604","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["GEO metadata verified with just verify-datasets on 2026-09-04; evidence is in references_cache/GEO_GSE190760.md. The linked phase 1 trial treated ten participants, whereas this transcriptomic subset contains seven. No raw-data reanalysis was performed. Without a randomized steroid comparison, immune associations do not isolate prophylactic prednisone efficacy."],"contexts":[{"id":"disorder:Hemophilia_B","name":"Hemophilia B","kind":"Disorder","source_path":"kb/disorders/Hemophilia_B.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hemophilia_B.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hemophilia_B.html#dataset-geo-gse190760"}],"context_names":["Hemophilia B"],"disease_names":["Hemophilia B"],"disease_name":"Hemophilia B","same_context_model_ids":["model:kb/disorders/Hemophilia_B.yaml:Leyden F9 promoter transactivation assays","model:kb/disorders/Hemophilia_B.yaml:Purified and plasma FIX-Padua cofactor-dependence assays"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Hemophilia_B.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hemophilia_B.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hemophilia_B.html#dataset-geo-gse190760"]},{"id":"dataset:geo:gse190786","accession":"geo:GSE190786","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE190786","title":"Transcriptome profiles of monocytes of Periodontal Ehlers–Danlos Syndrome patients","alternate_titles":[],"description":"RNA sequencing of patient-derived monocytes from 2 pEDS patients and 3 normal controls, identifying differentially expressed genes related to periodontal host defense, inflammatory response, skin disease, and vascular development.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:35571048"],"publication_contexts":[{"context_id":"disorder:Periodontal_Ehlers-Danlos_Syndrome","publication":"PMID:35571048"}],"publication":"PMID:35571048","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35571048","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE190786","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE190786","reference_title":null,"supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"our study performed transcriptome profiling by RNA sequencing of patient-derived monocytes from 2 pEDS patients and 3 normal controls","explanation":"GEO record describes the cohort and assay underlying this dataset."}],"notes":[],"contexts":[{"id":"disorder:Periodontal_Ehlers-Danlos_Syndrome","name":"Periodontal Ehlers-Danlos Syndrome","kind":"Disorder","source_path":"kb/disorders/Periodontal_Ehlers-Danlos_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Periodontal_Ehlers-Danlos_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Periodontal_Ehlers-Danlos_Syndrome.html#dataset-geo-gse190786"}],"context_names":["Periodontal Ehlers-Danlos Syndrome"],"disease_names":["Periodontal Ehlers-Danlos Syndrome"],"disease_name":"Periodontal Ehlers-Danlos Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Periodontal_Ehlers-Danlos_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Periodontal_Ehlers-Danlos_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Periodontal_Ehlers-Danlos_Syndrome.html#dataset-geo-gse190786"]},{"id":"dataset:geo:gse191041","accession":"geo:GSE191041","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE191041","title":"Cell function and identity revealed by comparative scRNA-seq analysis in human nasal, bronchial and epididymis epithelia. [scRNA-Seq]","alternate_titles":[],"description":"Single-cell RNA-seq characterization of human nasal epithelial cell populations including basal, secretory, goblet, and ciliated cells. Provides a reference atlas of the cell types present in normal nasal epithelium, relevant to understanding the cellular composition lost following turbinate resection in ENS.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"CL:2000094","label":"nasal cavity respiratory epithelium epithelial cell of viscerocranial mucosa","display_label":"nasal cavity respiratory epithelium epithelial cell","url":"http://purl.obolibrary.org/obo/CL_2000094"}],"sample_type_labels":["nasal cavity respiratory epithelium epithelial cell of viscerocranial mucosa"],"sample_counts":[7],"sample_count":7,"conditions":["normal human nasal epithelium","normal human bronchial epithelium"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:35597096"],"publication_contexts":[{"context_id":"disorder:Empty_Nose_Syndrome","publication":"PMID:35597096"}],"publication":"PMID:35597096","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35597096","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["No ENS-specific omics datasets exist. This reference atlas of normal human nasal epithelial cell types is relevant for understanding the cellular populations disrupted by turbinate surgery."],"contexts":[{"id":"disorder:Empty_Nose_Syndrome","name":"Empty Nose Syndrome","kind":"Disorder","source_path":"kb/disorders/Empty_Nose_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Empty_Nose_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Empty_Nose_Syndrome.html#dataset-geo-gse191041"}],"context_names":["Empty Nose Syndrome"],"disease_names":["Empty Nose Syndrome"],"disease_name":"Empty Nose Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Empty_Nose_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Empty_Nose_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Empty_Nose_Syndrome.html#dataset-geo-gse191041"]},{"id":"dataset:geo:gse191082","accession":"geo:GSE191082","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE191082","title":"Specific methylation marks in promoter regions are associated to the pathogenic process of Chronic Chagas disease Cardiomyopathy by modifying transcription factor binding patterns [methylation]","alternate_titles":[],"description":"Chagas disease, caused by Trypanosoma cruzi, is an endemic parasitical disease of Latin America, affecting 7 million people. Although most patients are asymptomatic, 30% develop complications, including Chronic Chagasic Cardiomyopathy (CCC), which ranges from moderate to severe stages depending on the cardiac ejection fraction. The pathogenic process remains poorly understood, although genetic and epigenetic factors have already been proposed. Based on bulk RNA-seq and EPIC methylation data, we investigated the genetic and epigenetic deregulations present in the moderate and severe stages of CCC.","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[158],"sample_count":158,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:36072583"],"publication_contexts":[{"context_id":"disorder:Chagas_Disease","publication":"PMID:36072583"}],"publication":"PMID:36072583","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36072583","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Chagas disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Chagas_Disease","name":"Chagas disease","kind":"Disorder","source_path":"kb/disorders/Chagas_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chagas_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chagas_disease.html#dataset-geo-gse191082"}],"context_names":["Chagas disease"],"disease_names":["Chagas disease"],"disease_name":"Chagas disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chagas_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chagas_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chagas_disease.html#dataset-geo-gse191082"]},{"id":"dataset:geo:gse192971","accession":"geo:GSE192971","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE192971","title":"Regulatory role of energy metabolism in skeletal development","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:36711926"],"publication_contexts":[{"context_id":"disorder:Spondyloepiphyseal_Dysplasia_Nishimura_Type","publication":"PMID:36711926"}],"publication":"PMID:36711926","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36711926","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["RNA-seq from Ldha and Acly conditional-knockout chondrocytes, the surrogate models used to test the metabolic branch. Relevant to this disease as the evidence base for the acetyl-CoA account rather than as a measurement of the miR-140 genotype."],"contexts":[{"id":"disorder:Spondyloepiphyseal_Dysplasia_Nishimura_Type","name":"Spondyloepiphyseal Dysplasia, Nishimura Type","kind":"Disorder","source_path":"kb/disorders/Spondyloepiphyseal_Dysplasia_Nishimura_Type.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Spondyloepiphyseal_Dysplasia_Nishimura_Type.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Spondyloepiphyseal_Dysplasia,_Nishimura_Type.html#dataset-geo-gse192971"}],"context_names":["Spondyloepiphyseal Dysplasia, Nishimura Type"],"disease_names":["Spondyloepiphyseal Dysplasia, Nishimura Type"],"disease_name":"Spondyloepiphyseal Dysplasia, Nishimura Type","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Spondyloepiphyseal_Dysplasia_Nishimura_Type.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Spondyloepiphyseal_Dysplasia_Nishimura_Type.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Spondyloepiphyseal_Dysplasia,_Nishimura_Type.html#dataset-geo-gse192971"]},{"id":"dataset:geo:gse193398","accession":"geo:GSE193398","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE193398","title":"Comparative RNA sequencing identifies superior cytocidal mechanisms of imatinib over rapamycin in Pulmonary Lymphangioleiomyomatosis (LAM) Tumor Cells","alternate_titles":[],"description":"We report results of RNA sequencing analysis of serum starved pulmonary LAM tumor cells comparatively treated for 24hrs at 37C and 5% CO2 with rapamycin (0.05uM and 1uM) and tyrosine kinase inhibitor (TKI) imatinib (1uM, 5uM, and 10uM). Experiments were done in duplicates per drug concentration. This study was performed to investigate the biological mechanisms underlying superior cytocidal capabilities of the TKI over FDA-approved rapamycin by inhibiting receptor tyrosine kinases on mesenchymal tumorigenic cells in Tuberous Sclerosis and Lymphangioleiomyomatosis (LAM) diseases.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37127876"],"publication_contexts":[{"context_id":"disorder:Lymphangioleiomyomatosis","publication":"PMID:37127876"}],"publication":"PMID:37127876","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37127876","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Lymphangioleiomyomatosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Lymphangioleiomyomatosis","name":"Lymphangioleiomyomatosis","kind":"Disorder","source_path":"kb/disorders/Lymphangioleiomyomatosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Lymphangioleiomyomatosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Lymphangioleiomyomatosis.html#dataset-geo-gse193398"}],"context_names":["Lymphangioleiomyomatosis"],"disease_names":["Lymphangioleiomyomatosis"],"disease_name":"Lymphangioleiomyomatosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Lymphangioleiomyomatosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Lymphangioleiomyomatosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Lymphangioleiomyomatosis.html#dataset-geo-gse193398"]},{"id":"dataset:geo:gse193782","accession":"geo:GSE193782","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE193782","title":"ScRNA-seq Expression of APOC2 and IFI27 Identifies Four Alveolar Macrophage Superclusters in Cystic Fibrosis and Healthy BALF","alternate_titles":[],"description":"Single-cell RNA sequencing dataset of bronchoalveolar lavage cells from healthy controls and uninflamed cystic fibrosis subjects used to define alveolar macrophage superclusters and immune-cell heterogeneity.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0002048","label":"lung","display_label":"lung (bronchoalveolar lavage cells)","url":"http://purl.obolibrary.org/obo/UBERON_0002048"}],"sample_type_labels":["lung"],"sample_counts":[7],"sample_count":7,"conditions":["cystic fibrosis","healthy control"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:35820705"],"publication_contexts":[{"context_id":"disorder:Cystic_Fibrosis","publication":"PMID:35820705"}],"publication":"PMID:35820705","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35820705","publication_status":"Publication recorded","findings":[{"statement":"BAL single-cell profiling identifies conserved alveolar macrophage superclusters across healthy and uninflamed CF subjects","evidence":[{"reference":"PMID:35820705","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/35820705","reference_title":"ScRNA-seq expression of IFI27 and APOC2 identifies four alveolar macrophage superclusters in healthy BALF.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"We performed single-cell RNA sequencing on 113,213 bronchoalveolar lavage cells from four healthy and three uninflamed cystic fibrosis subjects and identified two MARCKS+LGMN+IMs, FOLR2+SELENOP+ and SPP1+PLA2G7+ IMs, monocyte subtypes, DC1, DC2, migDCs, plasmacytoid DCs, lymphocytes, epithelial cells, and four AM superclusters (families) based on the gene expression of IFI27 and APOC2","explanation":"The study reports core BAL immune-cell architecture including four alveolar macrophage superclusters in CF-context samples."}]}],"findings_text":["BAL single-cell profiling identifies conserved alveolar macrophage superclusters across healthy and uninflamed CF subjects"],"evidence":[{"reference":"PMID:35820705","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/35820705","reference_title":"ScRNA-seq expression of IFI27 and APOC2 identifies four alveolar macrophage superclusters in healthy BALF.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"We performed single-cell RNA sequencing on 113,213 bronchoalveolar lavage cells from four healthy and three uninflamed cystic fibrosis subjects and identified two MARCKS+LGMN+IMs, FOLR2+SELENOP+ and SPP1+PLA2G7+ IMs, monocyte subtypes, DC1, DC2, migDCs, plasmacytoid DCs, lymphocytes, epithelial cells, and four AM superclusters (families) based on the gene expression of IFI27 and APOC2","explanation":"The study reports core BAL immune-cell architecture including four alveolar macrophage superclusters in CF-context samples."}],"notes":["Provides CF-relevant BAL immune-cell state reference for airway inflammation mechanisms."],"contexts":[{"id":"disorder:Cystic_Fibrosis","name":"Cystic Fibrosis","kind":"Disorder","source_path":"kb/disorders/Cystic_Fibrosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cystic_Fibrosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cystic_Fibrosis.html#dataset-geo-gse193782"}],"context_names":["Cystic Fibrosis"],"disease_names":["Cystic Fibrosis"],"disease_name":"Cystic Fibrosis","same_context_model_ids":["model:kb/disorders/Cystic_Fibrosis.yaml:CF airway-on-chip microphysiological model","model:kb/disorders/Cystic_Fibrosis.yaml:NuLi/CuFi airway epithelial cell-line model","model:kb/disorders/Cystic_Fibrosis.yaml:Patient-derived airway organoid theratyping model"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Cystic_Fibrosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cystic_Fibrosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cystic_Fibrosis.html#dataset-geo-gse193782"]},{"id":"dataset:geo:gse193879","accession":"geo:GSE193879","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE193879","title":"Epigenetic Profiling Linked to Multisystem Inflammatory Syndrome in Children (MIS-C): A Multicenter, Retrospective Study","alternate_titles":[],"description":"Background: Most children and adolescents infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop a mild coronavirus disease 2019 (COVID-19) that usually does not require medical intervention. However, a small proportion of pediatric patients develop a severe clinical condition, Multisystem Inflammatory Syndrome in Children (MIS-C). The involvement of epigenetics in the control of the immune response and viral activity prompted us to carry out an epigenomic study to uncover target loci regulated by DNA methylation that could be altered upon the appearance of MIS-C.","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[127],"sample_count":127,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:35770252"],"publication_contexts":[{"context_id":"disorder:Multisystem_Inflammatory_Syndrome_in_Children_MIS-C","publication":"PMID:35770252"}],"publication":"PMID:35770252","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35770252","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Multisystem Inflammatory Syndrome in Children (MIS-C) (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Multisystem_Inflammatory_Syndrome_in_Children_MIS-C","name":"Multisystem Inflammatory Syndrome in Children (MIS-C)","kind":"Disorder","source_path":"kb/disorders/Multisystem_Inflammatory_Syndrome_in_Children_MIS-C.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Multisystem_Inflammatory_Syndrome_in_Children_MIS-C.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Multisystem_Inflammatory_Syndrome_in_Children_MIS-C.html#dataset-geo-gse193879"}],"context_names":["Multisystem Inflammatory Syndrome in Children (MIS-C)"],"disease_names":["Multisystem Inflammatory Syndrome in Children (MIS-C)"],"disease_name":"Multisystem Inflammatory Syndrome in Children (MIS-C)","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Multisystem_Inflammatory_Syndrome_in_Children_MIS-C.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Multisystem_Inflammatory_Syndrome_in_Children_MIS-C.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Multisystem_Inflammatory_Syndrome_in_Children_MIS-C.html#dataset-geo-gse193879"]},{"id":"dataset:geo:gse195436","accession":"geo:GSE195436","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE195436","title":"Circulating miR-499a-5p is a potential biomarker of MYH7-associated hypertrophic cardiomyopathy","alternate_titles":[],"description":"Plasma small-RNA sequencing in hypertrophic cardiomyopathy patients and controls, with downstream qRT-PCR stratified by causal gene. The dataset behind this entry's genotype-specific miR-499a-5p biochemical record.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[15],"sample_count":15,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:35409153"],"publication_contexts":[{"context_id":"disorder:Hypertrophic_Cardiomyopathy_1","publication":"PMID:35409153"}],"publication":"PMID:35409153","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35409153","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["DIRECT relevance: human patient plasma, MYH7 named in the study title and the genotype used as the stratifying variable."],"contexts":[{"id":"disorder:Hypertrophic_Cardiomyopathy_1","name":"Hypertrophic Cardiomyopathy 1","kind":"Disorder","source_path":"kb/disorders/Hypertrophic_Cardiomyopathy_1.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hypertrophic_Cardiomyopathy_1.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_1.html#dataset-geo-gse195436"}],"context_names":["Hypertrophic Cardiomyopathy 1"],"disease_names":["Hypertrophic Cardiomyopathy 1"],"disease_name":"Hypertrophic Cardiomyopathy 1","same_context_model_ids":["model:kb/disorders/Hypertrophic_Cardiomyopathy_1.yaml:MYH7 G256E gene-edited hiPSC-cardiomyocyte multiscale platform","model:kb/disorders/Hypertrophic_Cardiomyopathy_1.yaml:MYH7 R403Q and TNNT2 R92Q hiPSC-cardiomyocyte engineered heart tissue","model:kb/disorders/Hypertrophic_Cardiomyopathy_1.yaml:MYH7 R403Q hiPSC-cardiomyocyte cardiac microtissue with wild-type fibroblasts"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Hypertrophic_Cardiomyopathy_1.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hypertrophic_Cardiomyopathy_1.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_1.html#dataset-geo-gse195436"]},{"id":"dataset:geo:gse195455","accession":"geo:GSE195455","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE195455","title":"MEG3 activates necroptosis in human neuron xenografts modeling Alzheimer's disease","alternate_titles":[],"description":"RNA-seq of human H9-derived neurons seven days after transduction with either a control virus or a MEG3 lentiviral vector, isolating the transcriptional consequence of MEG3 gain of function in human neurons.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"Homo sapiens","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37708272"],"publication_contexts":[{"context_id":"disorder:Alzheimer_Disease","publication":"PMID:37708272"}],"publication":"PMID:37708272","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37708272","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["The causal arm of the necroptosis model, and open access. Its value is as a reference signature: the programme MEG3 overexpression induces in human neurons can be scored against human Alzheimer neurons in the atlases above, which is the actual discriminating test. Note the parent SuperSeries geo:GSE195458 also contains xenograft bulk RNA-seq (geo:GSE195457); the study deposited no human post-mortem cohort of its own, so its claim that MEG3 is raised in patients is not backed by a deposited human dataset."],"contexts":[{"id":"disorder:Alzheimer_Disease","name":"Alzheimer Disease","kind":"Disorder","source_path":"kb/disorders/Alzheimer_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alzheimer_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Alzheimer_Disease.html#dataset-geo-gse195455"}],"context_names":["Alzheimer Disease"],"disease_names":["Alzheimer Disease"],"disease_name":"Alzheimer Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Alzheimer_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alzheimer_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Alzheimer_Disease.html#dataset-geo-gse195455"]},{"id":"dataset:geo:gse195695","accession":"geo:GSE195695","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE195695","title":"Inspecting VWF gene deep intronic region and in-depth study of the endothelial colony-forming cells to identify an underlying pathogenic molecular mechanism in a type 3 VWD patient","alternate_titles":[],"description":"A type 3 von Willebrand disease (VWD) index patient (IP) remains mutation-negative after completion of conventional diagnostic analysis, including multiplex ligation-dependent probe amplification and sequencing of the promotor, exons, and flanking intronic regions of VWF gene (VWF). In this study, we intended to elucidate causitive genetic defect through screening of the whole VWF (including complete intronic region), mRNA analysis, and study of the patient-derived endothelial colony-forming cells (ECFCs). The entire VWF was analyzed by next-generation sequencing (NGS) on an Illumina platform. The NGS revealed a novel variant in VWF intron 8 (997+118 T>G).","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:35328514"],"publication_contexts":[{"context_id":"disorder:Hereditary_von_Willebrand_Disease","publication":"PMID:35328514"}],"publication":"PMID:35328514","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35328514","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Hereditary von Willebrand Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Hereditary_von_Willebrand_Disease","name":"Hereditary von Willebrand Disease","kind":"Disorder","source_path":"kb/disorders/Hereditary_von_Willebrand_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hereditary_von_Willebrand_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hereditary_von_Willebrand_Disease.html#dataset-geo-gse195695"}],"context_names":["Hereditary von Willebrand Disease"],"disease_names":["Hereditary von Willebrand Disease"],"disease_name":"Hereditary von Willebrand Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hereditary_von_Willebrand_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hereditary_von_Willebrand_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hereditary_von_Willebrand_Disease.html#dataset-geo-gse195695"]},{"id":"dataset:geo:gse195791","accession":"geo:GSE195791","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE195791","title":"Transcriptional modifications between Treg from healthy donors (HD) and Treg from patients suffering from warm autoimmune hemolytic anemia (wAIHA)","alternate_titles":[],"description":"RNA sequencing of sorted circulating regulatory T cells in untreated warm AIHA and healthy controls. The publication reports four patients and four matched controls in the main transcriptomic comparison; the GEO sample_count is the repository record count. TCR and TNF pathway engagement was associated with reduced Treg suppression and reduced FOXP3 protein despite increased FOXP3 transcript levels; causality and post-translational mechanisms remain incompletely established.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[9],"sample_count":9,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37534543"],"publication_contexts":[{"context_id":"disorder:Autoimmune_Hemolytic_Anemia","publication":"PMID:37534543"}],"publication":"PMID:37534543","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37534543","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Autoimmune Hemolytic Anemia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Autoimmune_Hemolytic_Anemia","name":"Autoimmune Hemolytic Anemia","kind":"Disorder","source_path":"kb/disorders/Autoimmune_Hemolytic_Anemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autoimmune_Hemolytic_Anemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autoimmune_Hemolytic_Anemia.html#dataset-geo-gse195791"}],"context_names":["Autoimmune Hemolytic Anemia"],"disease_names":["Autoimmune Hemolytic Anemia"],"disease_name":"Autoimmune Hemolytic Anemia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Autoimmune_Hemolytic_Anemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autoimmune_Hemolytic_Anemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Autoimmune_Hemolytic_Anemia.html#dataset-geo-gse195791"]},{"id":"dataset:geo:gse195873","accession":"geo:GSE195873","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE195873","title":"Novel genetic variants of KHDC3L and other members of the subcortical maternal complex associated with Beckwith-Wiedemann syndrome or Pseudohypoparathyroidism 1B and multi-locus imprinting disturbances","alternate_titles":[],"description":"Beckwith–Wiedemann syndrome (BWS) and Pseudohypoparathyroidism type 1B (PHP1B) are imprinting disorders (ID) caused by deregulation of the imprinted gene clusters located at 11p15.5 and 20q13.32, respectively. In both of these diseases a subset of the patients is affected by multi-locus imprinting disturbances (MLID). In several families, MLID is associated with damaging variants of maternal-effect genes encoding protein components of the subcortical maternal complex (SCMC). However, frequency, penetrance and recurrence risks of these variants are still undefined.","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[18],"sample_count":18,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:35643636"],"publication_contexts":[{"context_id":"disorder:Pseudohypoparathyroidism","publication":"PMID:35643636"}],"publication":"PMID:35643636","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35643636","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Pseudohypoparathyroidism (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Pseudohypoparathyroidism","name":"Pseudohypoparathyroidism","kind":"Disorder","source_path":"kb/disorders/Pseudohypoparathyroidism.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pseudohypoparathyroidism.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pseudohypoparathyroidism.html#dataset-geo-gse195873"}],"context_names":["Pseudohypoparathyroidism"],"disease_names":["Pseudohypoparathyroidism"],"disease_name":"Pseudohypoparathyroidism","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Pseudohypoparathyroidism.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pseudohypoparathyroidism.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Pseudohypoparathyroidism.html#dataset-geo-gse195873"]},{"id":"dataset:geo:gse196051","accession":"geo:GSE196051","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE196051","title":"Recognition of copy-back defective interfering rabies virus genomes by RIG-I triggers efficient immune response against vaccine strains","alternate_titles":[],"description":"Using next-generation sequencing (NGS) combined with bioinformatics tools, we characterized two major 5’copy-back defective interfering (5’cb DI) genomes generated during SAD replication. Furthermore, we identified a specific interaction of 5’cb DI genomes and RIG-I that correlated with a high stimulation of the type I IFN signaling","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[36],"sample_count":36,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:38461968"],"publication_contexts":[{"context_id":"disorder:Rabies","publication":"PMID:38461968"}],"publication":"PMID:38461968","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38461968","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Rabies (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Rabies","name":"Rabies","kind":"Disorder","source_path":"kb/disorders/Rabies.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rabies.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Rabies.html#dataset-geo-gse196051"}],"context_names":["Rabies"],"disease_names":["Rabies"],"disease_name":"Rabies","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Rabies.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rabies.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Rabies.html#dataset-geo-gse196051"]},{"id":"dataset:geo:gse196052","accession":"geo:GSE196052","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE196052","title":"Single-cell profiling of hematopoietic cells in VEXAS syndrome","alternate_titles":[],"description":"Background and methods: VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome has been recently recognized as an adult-onset autoinflammatory syndrome due to somatic mutations affecting Ubiquitin Like Modifier Activating Enzyme 1 (UBA1) gene. Following-up studies have been mostly limited to case reports; transcriptome of especially hematopoiesis in VEXAS syndrome has not been well characterized. Results: We performed whole transcriptome sequencing of single bone marrow cells (BMMNCs) and enriched Lineage-CD34+ hematopoietic stem and progenitor cells (HSPCs) from nine patients included in the original VEXAS cohort.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[56],"sample_count":56,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37586319"],"publication_contexts":[{"context_id":"disorder:VEXAS_Syndrome","publication":"PMID:37586319"}],"publication":"PMID:37586319","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37586319","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for VEXAS Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:VEXAS_Syndrome","name":"VEXAS Syndrome","kind":"Disorder","source_path":"kb/disorders/VEXAS_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/VEXAS_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/VEXAS_Syndrome.html#dataset-geo-gse196052"}],"context_names":["VEXAS Syndrome"],"disease_names":["VEXAS Syndrome"],"disease_name":"VEXAS Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/VEXAS_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/VEXAS_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/VEXAS_Syndrome.html#dataset-geo-gse196052"]},{"id":"dataset:geo:gse196454","accession":"geo:GSE196454","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE196454","title":"Early Postnatal Alterations in Follicular Stress Response and Survival in a Mouse Model of Classic Galactosemia","alternate_titles":[],"description":"Primary ovarian insufficiency (POI) is characterized by accelerated loss of primordial follicles, which results in ovarian failure and concomitant menopause before age 40. 1-3% of females in the general population are diagnosed with POI and 80% of females with the inherited disease Classic Galactosemia (CG) will develop POI. CG is caused by mutations in the GALT gene encoding the enzyme galactose-1-phosphate uridylyltransferase. While dietary restriction of galactose is lifesaving in the neonatal period, the development of severe complications including POI is not mitigated. Additionally, the pattern of follicle loss have not been completely characterized.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Galactosemia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Galactosemia","name":"Galactosemia","kind":"Disorder","source_path":"kb/disorders/Galactosemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Galactosemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Galactosemia.html#dataset-geo-gse196454"}],"context_names":["Galactosemia"],"disease_names":["Galactosemia"],"disease_name":"Galactosemia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Galactosemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Galactosemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Galactosemia.html#dataset-geo-gse196454"]},{"id":"dataset:geo:gse196711","accession":"geo:GSE196711","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE196711","title":"Immune profiling of premalignant lesions in patients with Peutz-Jeghers Syndrome","alternate_titles":[],"description":"RNA sequencing was performed in a total of 26 colorectal tissues from 26 unrelated patients including PJS polyps (n=6), familial adenomatous polyposis (FAP) polyps (n=9), paracancerous colonic mucosae (ConA) (n=9) as well as non-PJS and non-FAP sporadic polyps (ConB) (n=5)","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[29],"sample_count":29,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39174496"],"publication_contexts":[{"context_id":"disorder:Peutz_Jeghers_Syndrome","publication":"PMID:39174496"}],"publication":"PMID:39174496","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39174496","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Peutz-Jeghers syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Peutz_Jeghers_Syndrome","name":"Peutz-Jeghers syndrome","kind":"Disorder","source_path":"kb/disorders/Peutz_Jeghers_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Peutz_Jeghers_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Peutz-Jeghers_syndrome.html#dataset-geo-gse196711"}],"context_names":["Peutz-Jeghers syndrome"],"disease_names":["Peutz-Jeghers syndrome"],"disease_name":"Peutz-Jeghers syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Peutz_Jeghers_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Peutz_Jeghers_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Peutz-Jeghers_syndrome.html#dataset-geo-gse196711"]},{"id":"dataset:geo:gse197105","accession":"geo:GSE197105","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE197105","title":"RNA sequencing of isolated brain endothelial cells from Smad4, Alk1, or Eng endothelial cell-specific knock-out mutants, respective wildtypes (WTs), and Angiopoietin-2 inhibition transcriptional changes.","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[39],"sample_count":39,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:3349","label":"ENG","display_label":"ENG","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/3349"}],"genes":["ENG"],"platforms":[],"platform":null,"publications":["PMID:37288572"],"publication_contexts":[{"context_id":"disorder:Hereditary_Hemorrhagic_Telangiectasia_Type_1","publication":"PMID:37288572"},{"context_id":"disorder:Hereditary_Hemorrhagic_Telangiectasia_Type_2","publication":"PMID:37288572"}],"publication":"PMID:37288572","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37288572","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Included for the Eng endothelial-cell-specific knockout arm, which is the HHT1-relevant portion; the Smad4 and Alk1 arms of the same series model JP-HHT and HHT2 respectively and are not evidence for this entry. Relevance triage matters here: a dataset search on \"hereditary hemorrhagic telangiectasia\" returns mostly Alk1- and Smad4-based series that resolve perfectly but concern the other molecular forms, and this was the only candidate in that search naming Eng. Note also that this is an endothelial conditional-knockout mouse, not the germline heterozygous state of human HHT1, so it speaks to endoglin's endothelial requirement rather than to haploinsufficiency.","Includes an Alk1 endothelial knockout arm alongside Eng and Smad4, so it is directly usable for the HHT1-versus-HHT2 contrast this entry curates. Only the Alk1 arm is HHT2; the Eng and Smad4 arms belong to other entities."],"contexts":[{"id":"disorder:Hereditary_Hemorrhagic_Telangiectasia_Type_1","name":"Hereditary Hemorrhagic Telangiectasia Type 1","kind":"Disorder","source_path":"kb/disorders/Hereditary_Hemorrhagic_Telangiectasia_Type_1.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hereditary_Hemorrhagic_Telangiectasia_Type_1.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hereditary_Hemorrhagic_Telangiectasia_Type_1.html#dataset-geo-gse197105"},{"id":"disorder:Hereditary_Hemorrhagic_Telangiectasia_Type_2","name":"Hereditary Hemorrhagic Telangiectasia Type 2","kind":"Disorder","source_path":"kb/disorders/Hereditary_Hemorrhagic_Telangiectasia_Type_2.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hereditary_Hemorrhagic_Telangiectasia_Type_2.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hereditary_Hemorrhagic_Telangiectasia_Type_2.html#dataset-geo-gse197105"}],"context_names":["Hereditary Hemorrhagic Telangiectasia Type 1","Hereditary Hemorrhagic Telangiectasia Type 2"],"disease_names":["Hereditary Hemorrhagic Telangiectasia Type 1","Hereditary Hemorrhagic Telangiectasia Type 2"],"disease_name":"Hereditary Hemorrhagic Telangiectasia Type 1","same_context_model_ids":["model:kb/disorders/Hereditary_Hemorrhagic_Telangiectasia_Type_2.yaml:LUMCi029-A-3 isogenic hiPSC line carrying ACVRL1 c.143G>A (p.Gly48Glu)"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Hereditary_Hemorrhagic_Telangiectasia_Type_1.yaml","kb/disorders/Hereditary_Hemorrhagic_Telangiectasia_Type_2.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hereditary_Hemorrhagic_Telangiectasia_Type_1.yaml","https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hereditary_Hemorrhagic_Telangiectasia_Type_2.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hereditary_Hemorrhagic_Telangiectasia_Type_1.html#dataset-geo-gse197105","https://dismech.monarchinitiative.org/pages/disorders/Hereditary_Hemorrhagic_Telangiectasia_Type_2.html#dataset-geo-gse197105"]},{"id":"dataset:geo:gse197289","accession":"geo:GSE197289","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE197289","title":"Human and mouse trigeminal ganglia cell atlas implicates multiple cell types in migraine","alternate_titles":[],"description":"The sensitization of trigeminal ganglion neurons contributes to primary headache disorders such as migraine, but the specific neuronal and non-neuronal trigeminal subtypes involved remain unclear. We thus developed a cell atlas in which human and mouse trigeminal ganglia are transcriptionally and epigenomically profiled at single-cell resolution. These data describe evolutionarily conserved and human-specific gene expression patterns within each trigeminal ganglion cell type, as well as the transcription factors and gene regulatory elements that contribute to cell-type-specific gene expression.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[36],"sample_count":36,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:35349784"],"publication_contexts":[{"context_id":"disorder:Migraine","publication":"PMID:35349784"}],"publication":"PMID:35349784","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35349784","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Migraine (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. GEO reports both Homo sapiens and Mus musculus; structured organism is omitted because Dataset.organism is single-valued."],"contexts":[{"id":"disorder:Migraine","name":"Migraine","kind":"Disorder","source_path":"kb/disorders/Migraine.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Migraine.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Migraine.html#dataset-geo-gse197289"}],"context_names":["Migraine"],"disease_names":["Migraine"],"disease_name":"Migraine","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Migraine.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Migraine.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Migraine.html#dataset-geo-gse197289"]},{"id":"dataset:geo:gse197345","accession":"geo:GSE197345","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE197345","title":"Gene Expression Analysis of Laser Captired Purkinje Cells from the Post-Mortem Essential Tremor Cerebellum","alternate_titles":[],"description":"RNA-seq evaluation of enriched Purkinje cells from the post-mortem human cerebellum. Purkinje cells were removed via laser capture microdissection and pooled for RNA-extraction and sequencing. 24 ET patients and 16 controls healthy age matched were compared.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[40],"sample_count":40,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:36242761"],"publication_contexts":[{"context_id":"disorder:Essential_Tremor","publication":"PMID:36242761"}],"publication":"PMID:36242761","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36242761","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Essential Tremor (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Essential_Tremor","name":"Essential Tremor","kind":"Disorder","source_path":"kb/disorders/Essential_Tremor.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Essential_Tremor.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Essential_Tremor.html#dataset-geo-gse197345"}],"context_names":["Essential Tremor"],"disease_names":["Essential Tremor"],"disease_name":"Essential Tremor","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Essential_Tremor.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Essential_Tremor.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Essential_Tremor.html#dataset-geo-gse197345"]},{"id":"dataset:geo:gse197406","accession":"geo:GSE197406","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE197406","title":"Expression data from Wilson disease patients liver","alternate_titles":[],"description":"Microarray expression profiling of liver tissue from Wilson disease patients and controls.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0002107","label":"liver","display_label":"liver","url":"http://purl.obolibrary.org/obo/UBERON_0002107"}],"sample_type_labels":["liver"],"sample_counts":[15],"sample_count":15,"conditions":["Wilson disease","control liver tissue"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Includes 7 Wilson disease and 8 control liver samples."],"contexts":[{"id":"disorder:Wilsons_Disease","name":"Wilson Disease","kind":"Disorder","source_path":"kb/disorders/Wilsons_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Wilsons_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Wilson_Disease.html#dataset-geo-gse197406"}],"context_names":["Wilson Disease"],"disease_names":["Wilson Disease"],"disease_name":"Wilson Disease","same_context_model_ids":["model:kb/disorders/Wilsons_Disease.yaml:ATP7B H1069Q homozygous patient iPSC-derived hepatocyte-like cells","model:kb/disorders/Wilsons_Disease.yaml:ATP7B R778L patient iPSC-derived hepatocyte-like cells","model:kb/disorders/Wilsons_Disease.yaml:Wilson disease patient liver organoids with prime-edited ATP7B"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Wilsons_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Wilsons_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Wilson_Disease.html#dataset-geo-gse197406"]},{"id":"dataset:geo:gse197461","accession":"geo:GSE197461","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE197461","title":"Decipher heterogeneity of cervical squamous cell carcinoma and adenocarcinoma with different HPV status: combining scRNA and TCR-seq with 3D organoid","alternate_titles":[],"description":"Although adenocarcinoma of the cervix (ADC) exhibits a more malignant phenotype and poorer prognosis than squamous cell carcinoma (SCC), they are treated identically. This clinical dilemma calls for deeper investigation into differences between SCC and ADC. We studied 3 human papillomavirus (HPV)-positive SCC, 3 HPV-associated (HPVA) and 2 non-HPV-associated (NHPVA) ADC samples with single-cell RNA and T cell receptor sequencing plus 3D organoid verification. Notably, we revealed the malignant origin of epithelial cells characterized by stemness and poor differentiation and the potential mechanism of HPVA and NHPVA oncogenesis, deciphering differences between SCC and ADC.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[16],"sample_count":16,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37794698"],"publication_contexts":[{"context_id":"disorder:Cervical_Squamous_Cell_Carcinoma","publication":"PMID:37794698"}],"publication":"PMID:37794698","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37794698","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Cervical Squamous Cell Carcinoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Cervical_Squamous_Cell_Carcinoma","name":"Cervical Squamous Cell Carcinoma","kind":"Disorder","source_path":"kb/disorders/Cervical_Squamous_Cell_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cervical_Squamous_Cell_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cervical_Squamous_Cell_Carcinoma.html#dataset-geo-gse197461"}],"context_names":["Cervical Squamous Cell Carcinoma"],"disease_names":["Cervical Squamous Cell Carcinoma"],"disease_name":"Cervical Squamous Cell Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cervical_Squamous_Cell_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cervical_Squamous_Cell_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cervical_Squamous_Cell_Carcinoma.html#dataset-geo-gse197461"]},{"id":"dataset:geo:gse197981","accession":"geo:GSE197981","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE197981","title":"Innate type 2 immunity controls hair follicle commensalism by Demodex mites [2019]","alternate_titles":[],"description":"Mouse hair-follicle bulk RNA-seq from a study showing that ILC2-derived IL-13 restrains Demodex outgrowth; loss of this checkpoint drives inflammatory follicular programs and barrier loss. The study links its mouse findings to human rhinophymatous rosacea. Aligns with the Demodex Folliculorum Proliferation node.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":["Demodex-colonized mouse hair follicles","ILC2/IL-13-deficient Demodex-colonized hair follicles"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:36044899"],"publication_contexts":[{"context_id":"disorder:Rosacea","publication":"PMID:36044899"}],"publication":"PMID:36044899","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36044899","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE197981","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE197981","reference_title":"Innate type 2 immunity controls hair follicle commensalism by Demodex mites [2019]","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"Humans with rhinophymatous acne rosacea, a nasal inflammatory condition associated with a high burden of Demodex, had increased HF inflammatory cells with decreased type 2 cytokines, consistent with the inverse relationship seen in mice.","explanation":"GEO summary ties the mouse Demodex-commensalism transcriptome to the high mite burden of human phymatous rosacea, supporting the Demodex proliferation mechanism in this entry."}],"notes":["Two small (n=4) sibling sub-series from the same study, GSE198657 and GSE197982, exist in GEO; only the primary series is recorded here."],"contexts":[{"id":"disorder:Rosacea","name":"Rosacea","kind":"Disorder","source_path":"kb/disorders/Rosacea.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rosacea.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Rosacea.html#dataset-geo-gse197981"}],"context_names":["Rosacea"],"disease_names":["Rosacea"],"disease_name":"Rosacea","same_context_model_ids":["model:kb/disorders/Rosacea.yaml:HaCaT keratinocytes under simulated rosacea conditions","model:kb/disorders/Rosacea.yaml:Paired lesional and non-lesional papulopustular rosacea skin explants","model:kb/disorders/Rosacea.yaml:SZ95 sebocyte and live Demodex mite co-culture"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Rosacea.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rosacea.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Rosacea.html#dataset-geo-gse197981"]},{"id":"dataset:geo:gse198150","accession":"geo:GSE198150","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE198150","title":"The protease DDI2 regulates NRF1-metallothionein pathway in response to Cadmium toxicity in the liver","alternate_titles":[],"description":"RNA-seq profiling of liver tissue from liver-specific Ddi2 knockout and wild-type mice, investigating how the protease DDI2 regulates the NRF1-metallothionein pathway in response to cadmium toxicity. Identifies DDI2-mediated metallothionein activation as a protective mechanism against cadmium-induced hepatotoxicity.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[{"id":"UBERON:0002107","label":"liver","display_label":"liver","url":"http://purl.obolibrary.org/obo/UBERON_0002107"}],"sample_type_labels":["liver"],"sample_counts":[4],"sample_count":4,"conditions":["Ddi2 liver-specific knockout","wild-type control"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["Illumina HiSeq 2500"],"platform":"Illumina HiSeq 2500","publications":["PMID:36248746"],"publication_contexts":[{"context_id":"disorder:Cadmium_Poisoning","publication":"PMID:36248746"}],"publication":"PMID:36248746","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36248746","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["2 replicates per condition (WT vs Ddi2-KO). Demonstrates that DDI2 cleaves and activates NRF1 to drive metallothionein expression in response to cadmium, linking proteasome homeostasis to heavy metal detoxification."],"contexts":[{"id":"disorder:Cadmium_Poisoning","name":"Cadmium Poisoning","kind":"Disorder","source_path":"kb/disorders/Cadmium_Poisoning.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cadmium_Poisoning.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cadmium_Poisoning.html#dataset-geo-gse198150"}],"context_names":["Cadmium Poisoning"],"disease_names":["Cadmium Poisoning"],"disease_name":"Cadmium Poisoning","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cadmium_Poisoning.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cadmium_Poisoning.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cadmium_Poisoning.html#dataset-geo-gse198150"]},{"id":"dataset:geo:gse198258","accession":"geo:GSE198258","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE198258","title":"Bulk RNAseq analysis of hypertrophic cardiomyopathy (HCM) hiPSC-derived cardiomyocytes (hiPSC-CMs) and the isogenic control","alternate_titles":[],"description":"Day-15 bulk RNA-seq of HCM hiPSC-derived cardiomyocytes against their isogenic control, from the study of myosin heavy chain converter-domain mutations and early extracellular-matrix dynamics. Relevant to this entry's EGFR paracrine fibrosis arm because it profiles matrix changes at an early disease stage.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[4],"sample_count":4,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:35784482"],"publication_contexts":[{"context_id":"disorder:Hypertrophic_Cardiomyopathy_1","publication":"PMID:35784482"}],"publication":"PMID:35784482","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35784482","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["DIRECT relevance established from the linked publication rather than the GEO summary, which does not name the gene: the study is of myosin heavy chain converter-domain mutations, which are MYH7 alleles."],"contexts":[{"id":"disorder:Hypertrophic_Cardiomyopathy_1","name":"Hypertrophic Cardiomyopathy 1","kind":"Disorder","source_path":"kb/disorders/Hypertrophic_Cardiomyopathy_1.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hypertrophic_Cardiomyopathy_1.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_1.html#dataset-geo-gse198258"}],"context_names":["Hypertrophic Cardiomyopathy 1"],"disease_names":["Hypertrophic Cardiomyopathy 1"],"disease_name":"Hypertrophic Cardiomyopathy 1","same_context_model_ids":["model:kb/disorders/Hypertrophic_Cardiomyopathy_1.yaml:MYH7 G256E gene-edited hiPSC-cardiomyocyte multiscale platform","model:kb/disorders/Hypertrophic_Cardiomyopathy_1.yaml:MYH7 R403Q and TNNT2 R92Q hiPSC-cardiomyocyte engineered heart tissue","model:kb/disorders/Hypertrophic_Cardiomyopathy_1.yaml:MYH7 R403Q hiPSC-cardiomyocyte cardiac microtissue with wild-type fibroblasts"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Hypertrophic_Cardiomyopathy_1.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hypertrophic_Cardiomyopathy_1.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_1.html#dataset-geo-gse198258"]},{"id":"dataset:geo:gse198609","accession":"geo:GSE198609","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE198609","title":"Genomewide expression profiling from peripheral blood of multibacillary leprosy and Erythema Nodosum Leprosum (ENL) before and after thalidomide treatment.","alternate_titles":[],"description":"Acute inflammatory episodes are common in leprosy and complicate the course of the disease. Among these episodes, Erythema Nodosum Leprosum (ENL) is more common in multibacillary patients and can cause more systemic symptoms like fever, myalgia, edema, and pain. Today, ENL is managed with thalidomide and corticosteroids, yet the exact mechanisms behind ENL remain elusive and with few pharmacological options available. In this experiment, RNA was sequenced and gene expression was measured from the blood of multibacillary patients with and without ENL in a mixed design, comparing ENL to MB and ENL before and after thalidomide treatment for 7 days.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[37],"sample_count":37,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:35733868"],"publication_contexts":[{"context_id":"disorder:Leprosy","publication":"PMID:35733868"}],"publication":"PMID:35733868","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35733868","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Leprosy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Leprosy","name":"Leprosy","kind":"Disorder","source_path":"kb/disorders/Leprosy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Leprosy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Leprosy.html#dataset-geo-gse198609"}],"context_names":["Leprosy"],"disease_names":["Leprosy"],"disease_name":"Leprosy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Leprosy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Leprosy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Leprosy.html#dataset-geo-gse198609"]},{"id":"dataset:geo:gse199715","accession":"geo:GSE199715","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE199715","title":"Transcriptional profiling of multiple system atrophy cerebellar tissue highlights differences between the parkinsonian and cerebellar sub-types of the disease [cohort 2]","alternate_titles":[],"description":"Multiple system atrophy (MSA) is a rare adult-onset neurodegenerative disease of unknown cause, with no effective therapeutic options, and no cure. Limited work to date has attempted to characterize the transcriptional changes associated with the disease, which presents as either predominating parkinsonian (MSA-P) or cerebellar (MSC-C) symptoms. We report here the results of RNA expression profiling of cerebellar white matter (CWM) tissue from two independent cohorts of MSA patients (n = 66) and healthy controls (HC; n = 66). RNA samples from bulk brain tissue and from oligodendrocytes obtained by laser capture microdissection (LCM) were sequenced.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[94],"sample_count":94,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:32493431"],"publication_contexts":[{"context_id":"disorder:Multiple_System_Atrophy","publication":"PMID:32493431"}],"publication":"PMID:32493431","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32493431","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Multiple System Atrophy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Multiple_System_Atrophy","name":"Multiple System Atrophy","kind":"Disorder","source_path":"kb/disorders/Multiple_System_Atrophy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Multiple_System_Atrophy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Multiple_System_Atrophy.html#dataset-geo-gse199715"}],"context_names":["Multiple System Atrophy"],"disease_names":["Multiple System Atrophy"],"disease_name":"Multiple System Atrophy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Multiple_System_Atrophy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Multiple_System_Atrophy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Multiple_System_Atrophy.html#dataset-geo-gse199715"]},{"id":"dataset:geo:gse19982","accession":"geo:GSE19982","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE19982","title":"Gene expression discriminates chromophobe renal cell carcinoma and oncocytoma","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[30],"sample_count":30,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:20462447"],"publication_contexts":[{"context_id":"disorder:Chromophobe_Renal_Cell_Carcinoma","publication":"PMID:20462447"}],"publication":"PMID:20462447","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/20462447","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["GEO series matched because chromophobe renal cell carcinoma is named in the dataset's own title. Expression-based separation of chRCC from its principal benign mimic, oncocytoma - the diagnostic problem curated on the eosinophilic subtype and the CD117/CK7 immunoprofile finding. Relevance confirmed manually; retrieved 2026-08-15."],"contexts":[{"id":"disorder:Chromophobe_Renal_Cell_Carcinoma","name":"Chromophobe Renal Cell Carcinoma","kind":"Disorder","source_path":"kb/disorders/Chromophobe_Renal_Cell_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chromophobe_Renal_Cell_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chromophobe_Renal_Cell_Carcinoma.html#dataset-geo-gse19982"}],"context_names":["Chromophobe Renal Cell Carcinoma"],"disease_names":["Chromophobe Renal Cell Carcinoma"],"disease_name":"Chromophobe Renal Cell Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chromophobe_Renal_Cell_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chromophobe_Renal_Cell_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chromophobe_Renal_Cell_Carcinoma.html#dataset-geo-gse19982"]},{"id":"dataset:geo:gse199925","accession":"geo:GSE199925","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE199925","title":"Desmosomal protein degradation as underlying causes of arrhythmogenic cardiomyopathy [PKP2 c.1755delA/WT and WT]","alternate_titles":[],"description":"Arrhythmogenic cardiomyopathy (ACM) is an inherited progressive cardiomyopathy. The pathophysiological events are well understood, yet the underlying molecular mechanisms remain undefined. Here we use patient originated hiPSC-derived cardiomyocytes bearing a pathogenic PKP2 mutation (PKP2 c.2013delC/WT), a corresponding knock-in mouse model carrying the equivalent murine mutation (Pkp2 c.1755delA/WT), and human explanted ACM hearts, to identify disease driving mechanisms. Pkp2 c.1755delA/WT mice over time displayed signs of ACM as observed by cardiac dysfunction and pathological remodeling.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[8],"sample_count":8,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:36947592"],"publication_contexts":[{"context_id":"disorder:PKP2_Cardiomyopathy","publication":"PMID:36947592"}],"publication":"PMID:36947592","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36947592","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for PKP2 Cardiomyopathy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:PKP2_Cardiomyopathy","name":"PKP2_Cardiomyopathy","kind":"Disorder","source_path":"kb/disorders/PKP2_Cardiomyopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/PKP2_Cardiomyopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/PKP2_Cardiomyopathy.html#dataset-geo-gse199925"}],"context_names":["PKP2_Cardiomyopathy"],"disease_names":["PKP2_Cardiomyopathy"],"disease_name":"PKP2_Cardiomyopathy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/PKP2_Cardiomyopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/PKP2_Cardiomyopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/PKP2_Cardiomyopathy.html#dataset-geo-gse199925"]},{"id":"dataset:geo:gse199978","accession":"geo:GSE199978","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE199978","title":"A novel somatic mutation in GNAQ in Sturge-Weber Syndrome provides insight into disease pathogenesis","alternate_titles":[],"description":"Sturge-Weber syndrome (SWS) is a sporadic, congenital, neuro-cutaneous disorder characterized by a mosaic, capillary malformation. SWS and isolated capillary malformations are caused by a somatic activating mutation in GNAQ encoding the G protein subunit alpha-q protein. The missense mutation R183Q is the sole GNAQ mutation identified thus far in affected tissues of 90% of SWS patients. In this study, we sequenced skin biopsies of affected capillary malformations from 9 patients. We identified the R183Q mutation in nearly all samples, but one sample exhibited a Q209R mutation.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[15],"sample_count":15,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:35635655"],"publication_contexts":[{"context_id":"disorder:Sturge-Weber_Syndrome","publication":"PMID:35635655"}],"publication":"PMID:35635655","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35635655","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Sturge-Weber Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Sturge-Weber_Syndrome","name":"Sturge-Weber Syndrome","kind":"Disorder","source_path":"kb/disorders/Sturge-Weber_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sturge-Weber_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Sturge-Weber_Syndrome.html#dataset-geo-gse199978"}],"context_names":["Sturge-Weber Syndrome"],"disease_names":["Sturge-Weber Syndrome"],"disease_name":"Sturge-Weber Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Sturge-Weber_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sturge-Weber_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Sturge-Weber_Syndrome.html#dataset-geo-gse199978"]},{"id":"dataset:geo:gse199991","accession":"geo:GSE199991","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE199991","title":"Dental caries as a risk factor for bacterial blood stream infection (BSI) in children undergoing hematopoietic cell transplantation (HCT)","alternate_titles":[],"description":"Background. Hematopoietic cell transplantation (HCT) is a potentially curative therapy for a wide range of pediatric malignant and nonmalignant diseases. However, complications, including blood stream infection (BSI) remain a major cause of morbidity and mortality. While certain bacteria that are abundant in the oral microbiome, such as S. mitis, can cause BSI, the role of the oral microbial community in the etiology of BSI is not well understood. The finding that the use of xylitol wipes, which specifically targets the cariogenic bacteria S. mutans is associated with reduced BSI in pediatric patients, lead us to investigate dental caries as a risk factor for BSI. Methods.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[8],"sample_count":8,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Dental Caries (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Dental_Caries","name":"Dental Caries","kind":"Disorder","source_path":"kb/disorders/Dental_Caries.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dental_Caries.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Dental_Caries.html#dataset-geo-gse199991"}],"context_names":["Dental Caries"],"disease_names":["Dental Caries"],"disease_name":"Dental Caries","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Dental_Caries.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dental_Caries.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Dental_Caries.html#dataset-geo-gse199991"]},{"id":"dataset:geo:gse200075","accession":"geo:GSE200075","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE200075","title":"A human autoimmune organoid model reveals IL-7 function in celiac disease","alternate_titles":[],"description":"In vitro models of autoimmunity are constrained by an inability to culture affected epithelium alongside the complex tissue-resident immune microenvironment. Celiac disease (CeD) is an autoimmune disease where dietary gluten-derived peptides bind the MHC- II molecules HLA-DQ2 or -DQ8 to initiate immune-mediated duodenal mucosal injury. Here, we generated air-liquid interface (ALI) duodenal organoids from endoscopic biopsies that preserve epithelium alongside native mesenchyme and tissue-resident immune cells as a unit without requiring reconstitution. The ALI organoid immune diversity spanned T, B, plasma, NK and myeloid cells with extensive T and B cell receptor repertoires.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[30],"sample_count":30,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39048815"],"publication_contexts":[{"context_id":"disorder:Celiac_Disease","publication":"PMID:39048815"}],"publication":"PMID:39048815","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39048815","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Celiac Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Celiac_Disease","name":"Celiac Disease","kind":"Disorder","source_path":"kb/disorders/Celiac_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Celiac_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Celiac_Disease.html#dataset-geo-gse200075"}],"context_names":["Celiac Disease"],"disease_names":["Celiac Disease"],"disease_name":"Celiac Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Celiac_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Celiac_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Celiac_Disease.html#dataset-geo-gse200075"]},{"id":"dataset:geo:gse200252","accession":"geo:GSE200252","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE200252","title":"Loss of Mitochondrial Fatty Acid Beta-Oxidation Protein Short Chain Enoyl-CoA Hydratase Disrupts Oxidative Phosphorylation Protein Complex Stability and Function","alternate_titles":[],"description":"Bulk RNA-seq of ECHS1-null human cells and patient fibroblasts showing secondary disruption of the TCA cycle, mitophagy, nucleotide synthesis, and OXPHOS complexes I and IV — evidence for the secondary mitochondrial/OXPHOS destabilization underlying the Leigh-like phenotype.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:35962613"],"publication_contexts":[{"context_id":"disorder:ECHS1_Deficiency","publication":"PMID:35962613"}],"publication":"PMID:35962613","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35962613","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Organism: human (CRISPR-edited cells and patient fibroblasts). NCBI GEO."],"contexts":[{"id":"disorder:ECHS1_Deficiency","name":"ECHS1 Deficiency","kind":"Disorder","source_path":"kb/disorders/ECHS1_Deficiency.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/ECHS1_Deficiency.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/ECHS1_Deficiency.html#dataset-geo-gse200252"}],"context_names":["ECHS1 Deficiency"],"disease_names":["ECHS1 Deficiency"],"disease_name":"ECHS1 Deficiency","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/ECHS1_Deficiency.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/ECHS1_Deficiency.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/ECHS1_Deficiency.html#dataset-geo-gse200252"]},{"id":"dataset:geo:gse200642","accession":"geo:GSE200642","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE200642","title":"Integrative single cell and spatial transcriptomic analysis reveal reciprocal microglia-plasma cell crosstalk in the mouse brain during chronic Trypanosoma brucei infection","alternate_titles":[],"description":"Human African trypanosomiasis, or sleeping sickness, is caused by the protozoan parasite Trypanosoma brucei and induces profound reactivity of glial cells and neuroinflammation when the parasites colonise the central nervous system. However, the transcriptional and functional responses of the brain to chronic T. brucei infection remain poorly understood. By integrating single cell and spatial transcriptomics of the mouse brain, we identified that glial responses triggered by infection are readily detected in the proximity to the circumventricular organs, including the lateral and 3rd ventricle. This coincides with the spatial localisation of both slender and stumpy forms of T. brucei.","alternate_descriptions":[],"data_types":["SPATIAL_TRANSCRIPTOMICS"],"data_type_labels":["Spatially resolved transcriptomics"],"data_type_label":"Spatially resolved transcriptomics","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[9],"sample_count":9,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:36180478"],"publication_contexts":[{"context_id":"disorder:Human_African_Trypanosomiasis","publication":"PMID:36180478"}],"publication":"PMID:36180478","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36180478","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Human African trypanosomiasis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Human_African_Trypanosomiasis","name":"Human African trypanosomiasis","kind":"Disorder","source_path":"kb/disorders/Human_African_Trypanosomiasis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Human_African_Trypanosomiasis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Human_African_trypanosomiasis.html#dataset-geo-gse200642"}],"context_names":["Human African trypanosomiasis"],"disease_names":["Human African trypanosomiasis"],"disease_name":"Human African trypanosomiasis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Human_African_Trypanosomiasis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Human_African_Trypanosomiasis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Human_African_trypanosomiasis.html#dataset-geo-gse200642"]},{"id":"dataset:geo:gse200674","accession":"geo:GSE200674","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE200674","title":"Modelling of pigmentation disorders associated with MITF mutation in Waaredenburg Syndrome revealed an impaired melanogenesis pathway in iPS-derived melanocytes","alternate_titles":[],"description":"Waardenburg Syndrome (WS) is a rare genetic disorder that leads to congenital hearing loss and pigmentation defects. MITF is one of its pathogenic genes. While studied extensively in animal models, its pathogenic mechanism still poorly described in humans due to the challenges in accessing embryonic tissues. In recent years, patient-derived human induced pluripotent stem cells(iPSCs) technology offers a promising approach for modeling human melanocyte development and hereditary disease. In this work, we make use of iPSCs derived from one WS patient carrying a heterozygous mutation in MITF gene.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[18],"sample_count":18,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37559350"],"publication_contexts":[{"context_id":"disorder:MITF_Waardenburg_Tietz_Spectrum","publication":"PMID:37559350"}],"publication":"PMID:37559350","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37559350","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for MITF Waardenburg-Tietz Spectrum (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:MITF_Waardenburg_Tietz_Spectrum","name":"MITF Waardenburg-Tietz Spectrum","kind":"Disorder","source_path":"kb/disorders/MITF_Waardenburg_Tietz_Spectrum.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MITF_Waardenburg_Tietz_Spectrum.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/MITF_Waardenburg-Tietz_Spectrum.html#dataset-geo-gse200674"}],"context_names":["MITF Waardenburg-Tietz Spectrum"],"disease_names":["MITF Waardenburg-Tietz Spectrum"],"disease_name":"MITF Waardenburg-Tietz Spectrum","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/MITF_Waardenburg_Tietz_Spectrum.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MITF_Waardenburg_Tietz_Spectrum.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/MITF_Waardenburg-Tietz_Spectrum.html#dataset-geo-gse200674"]},{"id":"dataset:geo:gse200809","accession":"geo:GSE200809","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE200809","title":"The human liver circadian transcriptome and its carcinogenic perturbation by hepatitis C virus infection (RNA-Seq I)","alternate_titles":[],"description":"Chronic liver disease and cancer are global health challenges. The role of the circadian clock (CC) as a regulator of physiology and disease is well established in animal models. However, in human liver the identity of circadian genes and their epigenetic regulation is unknown. Here, we unraveled the circadian transcriptome and epigenome of human hepatocytes using a human liver chimeric mouse model. We identified genes coding for transcription factors, chromatin modifiers, and critical enzymes which are expressed rhythmically in human hepatocytes, and which differ from the mouse liver circadian transcriptome.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39209804"],"publication_contexts":[{"context_id":"disorder:Hepatitis_C","publication":"PMID:39209804"}],"publication":"PMID:39209804","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39209804","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Hepatitis C (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Hepatitis_C","name":"Hepatitis C","kind":"Disorder","source_path":"kb/disorders/Hepatitis_C.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatitis_C.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hepatitis_C.html#dataset-geo-gse200809"}],"context_names":["Hepatitis C"],"disease_names":["Hepatitis C"],"disease_name":"Hepatitis C","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hepatitis_C.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatitis_C.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hepatitis_C.html#dataset-geo-gse200809"]},{"id":"dataset:geo:gse200907","accession":"geo:GSE200907","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE200907","title":"A non-synonymous SNP in SIRT6 predicts neurological severity in Friedreich ataxia","alternate_titles":[],"description":"Whole-transcriptome profiling of FRDA patients stratified by SIRT6 rs352493 genotype, supporting the modifier analysis of neurological severity.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[20],"sample_count":20,"conditions":["Friedreich ataxia, S46 SIRT6 variant","Friedreich ataxia, N46 SIRT6 variant"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:36133907"],"publication_contexts":[{"context_id":"disorder:Friedreich_Ataxia","publication":"PMID:36133907"}],"publication":"PMID:36133907","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36133907","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE200907","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE200907","reference_title":"A non-synonymous SNP in SIRT6 predicts neurological severity in Friedreich ataxia","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"S46 patients showed whole transcriptome differences compared to N46 patients, indicative of compensatory mechanisms against whole transcriptome changes seen in FRDA.","explanation":"The GEO summary describes the genotype-stratified patient transcriptome comparison this series holds."}],"notes":["Supports a genetic modifier of neurological severity acting alongside GAA repeat length, rather than a primary disease mechanism."],"contexts":[{"id":"disorder:Friedreich_Ataxia","name":"Friedreich Ataxia","kind":"Disorder","source_path":"kb/disorders/Friedreich_Ataxia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Friedreich_Ataxia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Friedreich_Ataxia.html#dataset-geo-gse200907"}],"context_names":["Friedreich Ataxia"],"disease_names":["Friedreich Ataxia"],"disease_name":"Friedreich Ataxia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Friedreich_Ataxia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Friedreich_Ataxia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Friedreich_Ataxia.html#dataset-geo-gse200907"]},{"id":"dataset:geo:gse201185","accession":"geo:GSE201185","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE201185","title":"Hit-and-run silencing of endogenous DUX4 by targeting DNA hypomethylation on D4Z4 repeats in facioscapulohumeral muscular dystrophy","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["MULTI_OMICS"],"data_type_labels":["Multi Omics"],"data_type_label":"Multi Omics","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[11],"sample_count":11,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Facioscapulohumeral Muscular Dystrophy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Facioscapulohumeral_Muscular_Dystrophy","name":"Facioscapulohumeral Muscular Dystrophy","kind":"Disorder","source_path":"kb/disorders/Facioscapulohumeral_Muscular_Dystrophy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Facioscapulohumeral_Muscular_Dystrophy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Facioscapulohumeral_Muscular_Dystrophy.html#dataset-geo-gse201185"}],"context_names":["Facioscapulohumeral Muscular Dystrophy"],"disease_names":["Facioscapulohumeral Muscular Dystrophy"],"disease_name":"Facioscapulohumeral Muscular Dystrophy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Facioscapulohumeral_Muscular_Dystrophy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Facioscapulohumeral_Muscular_Dystrophy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Facioscapulohumeral_Muscular_Dystrophy.html#dataset-geo-gse201185"]},{"id":"dataset:geo:gse201752","accession":"geo:GSE201752","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE201752","title":"Methylome and transcriptome profiling of giant cell arteritis monocytes reveals novel pathways involved in disease pathogenesis and molecular response to glucocorticoids [array]","alternate_titles":[],"description":"Giant cell arteritis (GCA) is a complex systemic vasculitis mediated by the interplay between both genetic and epigenetic factors. Monocytes are crucial players of the inflammation occurring in GCA. Therefore, characterization of the monocyte methylome and transcriptome in GCA would be helpful to better understand disease pathogenesis. We performed an integrated epigenome- and transcriptome-wide association study in CD14+ monocytes from 82 patients with GCA, cross-sectionally classified into three different clinical status (active, in remission with or without glucocorticoid (GC)-treatment), and 31 healthy controls.","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[113],"sample_count":113,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:35705375"],"publication_contexts":[{"context_id":"disorder:Giant_Cell_Arteritis","publication":"PMID:35705375"}],"publication":"PMID:35705375","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35705375","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Giant Cell Arteritis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Giant_Cell_Arteritis","name":"Giant Cell Arteritis","kind":"Disorder","source_path":"kb/disorders/Giant_Cell_Arteritis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Giant_Cell_Arteritis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Giant_Cell_Arteritis.html#dataset-geo-gse201752"}],"context_names":["Giant Cell Arteritis"],"disease_names":["Giant Cell Arteritis"],"disease_name":"Giant Cell Arteritis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Giant_Cell_Arteritis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Giant_Cell_Arteritis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Giant_Cell_Arteritis.html#dataset-geo-gse201752"]},{"id":"dataset:geo:gse201755","accession":"geo:GSE201755","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE201755","title":"Base Editing Correction of a Hypertrophic Cardiomyopathy-Causing MYH7 Mutation in Human Cardiomyocytes and Humanized Mice","alternate_titles":[],"description":"Transcriptomes from the adenine base-editing correction of MYH7 R403Q in patient-derived iPSC-cardiomyocytes and a humanized mouse model. The dataset behind the preclinical gene-editing treatment record in this entry.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"house mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[3],"sample_count":3,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:36797478"],"publication_contexts":[{"context_id":"disorder:Hypertrophic_Cardiomyopathy_1","publication":"PMID:36797478"}],"publication":"PMID:36797478","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36797478","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["DIRECT relevance: the archetypal CMH1 allele R403Q, named in the GEO series summary (the title says only \"a Hypertrophic Cardiomyopathy-Causing MYH7 Mutation\"). The organism is bound to Mus musculus because GEO records the series under that taxon; the study itself spans both patient-derived iPSC-cardiomyocytes and humanized mice, and the committed cache does not resolve which samples this accession holds. Read the accession before using it as a human dataset."],"contexts":[{"id":"disorder:Hypertrophic_Cardiomyopathy_1","name":"Hypertrophic Cardiomyopathy 1","kind":"Disorder","source_path":"kb/disorders/Hypertrophic_Cardiomyopathy_1.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hypertrophic_Cardiomyopathy_1.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_1.html#dataset-geo-gse201755"}],"context_names":["Hypertrophic Cardiomyopathy 1"],"disease_names":["Hypertrophic Cardiomyopathy 1"],"disease_name":"Hypertrophic Cardiomyopathy 1","same_context_model_ids":["model:kb/disorders/Hypertrophic_Cardiomyopathy_1.yaml:MYH7 G256E gene-edited hiPSC-cardiomyocyte multiscale platform","model:kb/disorders/Hypertrophic_Cardiomyopathy_1.yaml:MYH7 R403Q and TNNT2 R92Q hiPSC-cardiomyocyte engineered heart tissue","model:kb/disorders/Hypertrophic_Cardiomyopathy_1.yaml:MYH7 R403Q hiPSC-cardiomyocyte cardiac microtissue with wild-type fibroblasts"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Hypertrophic_Cardiomyopathy_1.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hypertrophic_Cardiomyopathy_1.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy_1.html#dataset-geo-gse201755"]},{"id":"dataset:geo:gse202179","accession":"geo:GSE202179","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE202179","title":"Antisense Oligonucleotide Rescue of CGG Expansion-Dependent FMR1 Mis-Splicing in Fragile X Syndrome Restores FMRP","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["MULTI_OMICS"],"data_type_labels":["Multi Omics"],"data_type_label":"Multi Omics","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[57],"sample_count":57,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37364131"],"publication_contexts":[{"context_id":"disorder:Fragile_X_Syndrome","publication":"PMID:37364131"}],"publication":"PMID:37364131","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37364131","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Fragile X Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Fragile_X_Syndrome","name":"Fragile X Syndrome","kind":"Disorder","source_path":"kb/disorders/Fragile_X_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fragile_X_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Fragile_X_Syndrome.html#dataset-geo-gse202179"}],"context_names":["Fragile X Syndrome"],"disease_names":["Fragile X Syndrome"],"disease_name":"Fragile X Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Fragile_X_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fragile_X_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Fragile_X_Syndrome.html#dataset-geo-gse202179"]},{"id":"dataset:geo:gse202617","accession":"geo:GSE202617","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE202617","title":"Gene expression of CD4+CD8+ Tfh cells in lesions of IgG4-related disease and CD4+CD8+ Tfh in tonsil.","alternate_titles":[],"description":"To further know features of CD4+CD8+ Double positive (DP)-Tfh cells in respective lymphoid tissues, we subsequently investigated transcriptomes of DP-Tfh cells in submandibular gland lesions of IgG4-RD in comparison to those of DP-Tfh cells in tonsils. Results showed that DP-Tfh cells of IgG4-RD lesions were more apt to present CTL-related genes such as Eomes and granzymes than DP-Tfh cells in tonsils. It was also noted that the level of CD70 in DP-Tfh cells of IgG4-RD lesions was higher than that of tonsillar DP-Tfh cells. Genes related to Tfh cell function were seemed to be presented in DP-Tfh cells of tonsils compared to DP-Tfh cells of IgG4-RD lesions.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[8],"sample_count":8,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:36091071"],"publication_contexts":[{"context_id":"disorder:IgG4-Related_Disease","publication":"PMID:36091071"}],"publication":"PMID:36091071","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36091071","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for IgG4-Related Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:IgG4-Related_Disease","name":"IgG4-Related Disease","kind":"Disorder","source_path":"kb/disorders/IgG4-Related_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/IgG4-Related_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/IgG4-Related_Disease.html#dataset-geo-gse202617"}],"context_names":["IgG4-Related Disease"],"disease_names":["IgG4-Related Disease"],"disease_name":"IgG4-Related Disease","same_context_model_ids":["model:kb/disorders/IgG4-Related_Disease.yaml:Anti-IL-1RA functional cell assays","model:kb/disorders/IgG4-Related_Disease.yaml:Human cholangiocyte protective-barrier assays","model:kb/disorders/IgG4-Related_Disease.yaml:Patient B-cell and fibroblast coculture","model:kb/disorders/IgG4-Related_Disease.yaml:Patient Tfh and B-cell coculture"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/IgG4-Related_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/IgG4-Related_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/IgG4-Related_Disease.html#dataset-geo-gse202617"]},{"id":"dataset:geo:gse202747","accession":"geo:GSE202747","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE202747","title":"Non-random distribution of mitochondrial m.3243A>G heteroplasmy in human retina and its impact on cellular phenotype","alternate_titles":[],"description":"Single-cell RNA-seq, mitochondrial single-cell ATAC-seq, and multimodal single-cell sequencing of retina and choroid from a MELAS donor eye and healthy controls, measuring per-cell m.3243A>G heteroplasmy alongside transcriptome and chromatin state. SuperSeries; the scRNA, scATAC, and multiome SubSeries are GSE202735, GSE202746, and GSE202886 and should not be curated separately.","alternate_descriptions":[],"data_types":["MULTI_OMICS"],"data_type_labels":["Multi Omics"],"data_type_label":"Multi Omics","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[36],"sample_count":36,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37289546"],"publication_contexts":[{"context_id":"disorder:MELAS_Syndrome","publication":"PMID:37289546"}],"publication":"PMID:37289546","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37289546","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:37289546","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/37289546","reference_title":"Multimodal single-cell analysis of nonrandom heteroplasmy distribution in human retinal mitochondrial disease.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"All neuroectoderm-derived neural cells exhibited a high percentage of the mutant variant. However, a subset of mesoderm-derived lineage, namely the vasculature of the choroid, was near homoplasmic for the WT allele.","explanation":"Shows heteroplasmy partitions non-randomly by cell lineage within one tissue, which is a candidate explanation for organ-level phenotype variation that bulk heteroplasmy cannot capture."}],"notes":["The most directly informative public dataset for the genotype-phenotype gap, because it measures heteroplasmy inside a tissue at single-cell resolution rather than in an accessible surrogate. Also bears on the stroke-like-episode mechanism controversy: in this tissue the neuroectoderm-derived neural cells carried a high mutant fraction while the mesoderm-derived choroidal vasculature was near-homoplasmic wild-type, which is the opposite of what a primarily vascular pathogenesis would predict. One donor eye, and retina is not cortex, so it is a lead rather than a settled answer."],"contexts":[{"id":"disorder:MELAS_Syndrome","name":"MELAS Syndrome","kind":"Disorder","source_path":"kb/disorders/MELAS_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MELAS_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/MELAS_Syndrome.html#dataset-geo-gse202747"}],"context_names":["MELAS Syndrome"],"disease_names":["MELAS Syndrome"],"disease_name":"MELAS Syndrome","same_context_model_ids":["model:kb/disorders/MELAS_Syndrome.yaml:m.3243A>G patient iPSC-derived neurons"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/MELAS_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MELAS_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/MELAS_Syndrome.html#dataset-geo-gse202747"]},{"id":"dataset:geo:gse202895","accession":"geo:GSE202895","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE202895","title":"Fragile X Syndrome Patient–Derived Neurons Developing in the Mouse Brain Show FMR1-Dependent Phenotypes","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[8],"sample_count":8,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:36372569"],"publication_contexts":[{"context_id":"disorder:Fragile_X_Syndrome","publication":"PMID:36372569"}],"publication":"PMID:36372569","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36372569","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Fragile X Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Fragile_X_Syndrome","name":"Fragile X Syndrome","kind":"Disorder","source_path":"kb/disorders/Fragile_X_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fragile_X_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Fragile_X_Syndrome.html#dataset-geo-gse202895"}],"context_names":["Fragile X Syndrome"],"disease_names":["Fragile X Syndrome"],"disease_name":"Fragile X Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Fragile_X_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fragile_X_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Fragile_X_Syndrome.html#dataset-geo-gse202895"]},{"id":"dataset:geo:gse202947","accession":"geo:GSE202947","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE202947","title":"Host inflammatory response is the major factor in the progression of Chlamydia psittaci pneumonia","alternate_titles":[],"description":"To clarify the host inflammatory response in psittacosis,we compared transcriptome data and concentrations of serum cytokines and chemokines in pneumonia and bronchitis cases.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[29],"sample_count":29,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:36119044"],"publication_contexts":[{"context_id":"disorder:Psittacosis","publication":"PMID:36119044"}],"publication":"PMID:36119044","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36119044","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Psittacosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Psittacosis","name":"Psittacosis","kind":"Disorder","source_path":"kb/disorders/Psittacosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Psittacosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Psittacosis.html#dataset-geo-gse202947"}],"context_names":["Psittacosis"],"disease_names":["Psittacosis"],"disease_name":"Psittacosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Psittacosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Psittacosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Psittacosis.html#dataset-geo-gse202947"]},{"id":"dataset:geo:gse203067","accession":"geo:GSE203067","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE203067","title":"Single-Cell Transcriptomic Analysis of Primary and Metastatic Tumor Ecosystems in Esophageal Squamous Cell Carcinoma","alternate_titles":[],"description":"We profiled the transcriptome of 85, 263 single cells from ESCC patients with lymph node metastasis (LNM) and clustered 7, 196 myeloid cells into 18 subclusters including nine for macrophage cells, one for neutrophils, two for monocytes, two for mast cells, one for tolerogenic dendritic cells, one for plasmacytoid dendritic cells and two for conventional dendritic cells. In this study, we not only provides a high-resolution landscape of the tumor, immune and stromal compartments in metastatic lymph node, but also highlights metastatic-specific patterns comparing with primary tumor.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[21],"sample_count":21,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:36709495"],"publication_contexts":[{"context_id":"disorder:Esophageal_Carcinoma","publication":"PMID:36709495"}],"publication":"PMID:36709495","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36709495","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Esophageal Carcinoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Esophageal_Carcinoma","name":"Esophageal Carcinoma","kind":"Disorder","source_path":"kb/disorders/Esophageal_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Esophageal_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Esophageal_Carcinoma.html#dataset-geo-gse203067"}],"context_names":["Esophageal Carcinoma"],"disease_names":["Esophageal Carcinoma"],"disease_name":"Esophageal Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Esophageal_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Esophageal_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Esophageal_Carcinoma.html#dataset-geo-gse203067"]},{"id":"dataset:geo:gse203126","accession":"geo:GSE203126","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE203126","title":"Chromosomal abnormalities and pregnancy outcomes for fetuses with gastrointestinal tract obstructions","alternate_titles":[],"description":"Fetal gastrointestinal tract obstructions (GITO) is the most frequently encountered gastrointestinal defects in prenatal. This study aimed to investigate the genetic disorders and pregnancy outcomes of fetal GITO. We reviewed data from 70 pregnancies who were referred for invasive prenatal testing due to fetal GITO. According to the levels of obstruction, they were classified into esophageal atresia/stenosis, duodenal atresia/stenosis, jejunal or ileal atresia/stenosis, and anal atresia. Traditional karyotyping was performed on all 70 pregnancies, and chromosomal microarray analysis (CMA) was performed on 32 of them in parallel.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[32],"sample_count":32,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:35783302"],"publication_contexts":[{"context_id":"disorder:Esophageal_Atresia","publication":"PMID:35783302"}],"publication":"PMID:35783302","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35783302","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Esophageal Atresia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Esophageal_Atresia","name":"Esophageal Atresia","kind":"Disorder","source_path":"kb/disorders/Esophageal_Atresia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Esophageal_Atresia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Esophageal_Atresia.html#dataset-geo-gse203126"}],"context_names":["Esophageal Atresia"],"disease_names":["Esophageal Atresia"],"disease_name":"Esophageal Atresia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Esophageal_Atresia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Esophageal_Atresia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Esophageal_Atresia.html#dataset-geo-gse203126"]},{"id":"dataset:geo:gse203432","accession":"geo:GSE203432","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE203432","title":"Exploring the microbiota pecularity in stool and biopsies of Eosinophilic Granulomatosis with Polyangiitis (EGPA) patients","alternate_titles":[],"description":"Human gut microbiome and mucosal immune-response dataset from EGPA, including stool profiling and intestinal biopsy-associated analyses.","alternate_descriptions":[],"data_types":["MULTI_OMICS"],"data_type_labels":["Multi Omics"],"data_type_label":"Multi Omics","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[45],"sample_count":45,"conditions":["eosinophilic granulomatosis with polyangiitis"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:35740247"],"publication_contexts":[{"context_id":"disorder:Eosinophilic_Granulomatosis_with_Polyangiitis","publication":"PMID:35740247"}],"publication":"PMID:35740247","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35740247","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:35740247","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/35740247","reference_title":"Gut Microbiota and Associated Mucosal Immune Response in Eosinophilic Granulomatosis with Polyangiitis (EGPA).","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"Here, we characterized the gut microbiota (GM) composition and the intestinal immune response in a cohort of EGPA patients.","explanation":"This supports GSE203432 as an EGPA-relevant public dataset centered on gut microbiota and mucosal immune features."}],"notes":[],"contexts":[{"id":"disorder:Eosinophilic_Granulomatosis_with_Polyangiitis","name":"Eosinophilic granulomatosis with polyangiitis","kind":"Disorder","source_path":"kb/disorders/Eosinophilic_Granulomatosis_with_Polyangiitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Eosinophilic_Granulomatosis_with_Polyangiitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Eosinophilic_granulomatosis_with_polyangiitis.html#dataset-geo-gse203432"}],"context_names":["Eosinophilic granulomatosis with polyangiitis"],"disease_names":["Eosinophilic granulomatosis with polyangiitis"],"disease_name":"Eosinophilic granulomatosis with polyangiitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Eosinophilic_Granulomatosis_with_Polyangiitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Eosinophilic_Granulomatosis_with_Polyangiitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Eosinophilic_granulomatosis_with_polyangiitis.html#dataset-geo-gse203432"]},{"id":"dataset:geo:gse203511","accession":"geo:GSE203511","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE203511","title":"Global gene expression changes in osteoblasts from fluoride-tolerant mice","alternate_titles":[],"description":"RNA-seq of MC3T3-E1 osteoblasts made fluoride-tolerant by gradient exposure. Note this profiles *resistance* rather than injury, so it bears on the disease by contrast; and it is a mouse cell line.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE203511","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE203511","reference_title":"Global gene expression changes in osteoblasts from fluoride-tolerant mice","supports":"SUPPORT","evidence_source":"OTHER","snippet":"Fluoride-tolerant MC3T3-E1 cells were developed by gradient fluoride exposure.","explanation":"The design, and the resistance framing that makes this a contrast resource rather than a model of the lesion. Graded OTHER as a repository record."}],"notes":[],"contexts":[{"id":"disorder:Skeletal_Fluorosis","name":"Skeletal Fluorosis","kind":"Disorder","source_path":"kb/disorders/Skeletal_Fluorosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Skeletal_Fluorosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Skeletal_Fluorosis.html#dataset-geo-gse203511"}],"context_names":["Skeletal Fluorosis"],"disease_names":["Skeletal Fluorosis"],"disease_name":"Skeletal Fluorosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Skeletal_Fluorosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Skeletal_Fluorosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Skeletal_Fluorosis.html#dataset-geo-gse203511"]},{"id":"dataset:geo:gse20376","accession":"geo:GSE20376","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE20376","title":"Gene expression and SNP profiling discriminates chromophobe renal cell carcinoma and oncocytoma","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[28],"sample_count":28,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["GEO series matched because chromophobe renal cell carcinoma is named in the dataset's own title. The SNP-profiling arm is the copy-number evidence underlying the characteristic monosomy pattern curated on the Recurrent Whole-Chromosome Loss node, and the paired oncocytoma samples are the comparator that makes the loss signature diagnostically useful. Relevance confirmed manually against the curated mechanism; retrieved 2026-08-15."],"contexts":[{"id":"disorder:Chromophobe_Renal_Cell_Carcinoma","name":"Chromophobe Renal Cell Carcinoma","kind":"Disorder","source_path":"kb/disorders/Chromophobe_Renal_Cell_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chromophobe_Renal_Cell_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chromophobe_Renal_Cell_Carcinoma.html#dataset-geo-gse20376"}],"context_names":["Chromophobe Renal Cell Carcinoma"],"disease_names":["Chromophobe Renal Cell Carcinoma"],"disease_name":"Chromophobe Renal Cell Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chromophobe_Renal_Cell_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chromophobe_Renal_Cell_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chromophobe_Renal_Cell_Carcinoma.html#dataset-geo-gse20376"]},{"id":"dataset:geo:gse204970","accession":"geo:GSE204970","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE204970","title":"MED12 Mutation Activates Tryptophan-Kynurenine-AHR pathway and Promotes Cell Growth in Human Uterine Leiomyoma.","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["MULTI_OMICS"],"data_type_labels":["Multi Omics"],"data_type_label":"Multi Omics","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[44],"sample_count":44,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37607000"],"publication_contexts":[{"context_id":"disorder:Uterine_Leiomyoma","publication":"PMID:37607000"}],"publication":"PMID:37607000","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37607000","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Uterine Leiomyoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Uterine_Leiomyoma","name":"Uterine Leiomyoma","kind":"Disorder","source_path":"kb/disorders/Uterine_Leiomyoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Uterine_Leiomyoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Uterine_Leiomyoma.html#dataset-geo-gse204970"}],"context_names":["Uterine Leiomyoma"],"disease_names":["Uterine Leiomyoma"],"disease_name":"Uterine Leiomyoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Uterine_Leiomyoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Uterine_Leiomyoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Uterine_Leiomyoma.html#dataset-geo-gse204970"]},{"id":"dataset:geo:gse205555","accession":"geo:GSE205555","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE205555","title":"Drug screening identifies tazarotene and bexarotene as therapeutic agents in Multiple Sulfatase Deficiency","alternate_titles":[],"description":"We analysed differences in gene expression upon treatment of MSD patient fibroblast lines with either tazarotene or adapalene and DMSO control (untreated condition)","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[62],"sample_count":62,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:36789546"],"publication_contexts":[{"context_id":"disorder:Multiple_Sulfatase_Deficiency","publication":"PMID:36789546"}],"publication":"PMID:36789546","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36789546","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Multiple Sulfatase Deficiency (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Multiple_Sulfatase_Deficiency","name":"Multiple Sulfatase Deficiency","kind":"Disorder","source_path":"kb/disorders/Multiple_Sulfatase_Deficiency.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Multiple_Sulfatase_Deficiency.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Multiple_Sulfatase_Deficiency.html#dataset-geo-gse205555"}],"context_names":["Multiple Sulfatase Deficiency"],"disease_names":["Multiple Sulfatase Deficiency"],"disease_name":"Multiple Sulfatase Deficiency","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Multiple_Sulfatase_Deficiency.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Multiple_Sulfatase_Deficiency.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Multiple_Sulfatase_Deficiency.html#dataset-geo-gse205555"]},{"id":"dataset:geo:gse205734","accession":"geo:GSE205734","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE205734","title":"Transcriptional and immune landscape of cardiac sarcoidosis","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["SPATIAL_TRANSCRIPTOMICS"],"data_type_labels":["Spatially resolved transcriptomics"],"data_type_label":"Spatially resolved transcriptomics","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[7],"sample_count":7,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:36111531"],"publication_contexts":[{"context_id":"disorder:Cardiac_Sarcoidosis","publication":"PMID:36111531"}],"publication":"PMID:36111531","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36111531","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Cardiac_Sarcoidosis (scripts/discover_datasets.py) and verified with just verify-datasets. Relevance triaged manually: cardiac sarcoidosis is named in the GEO series title and the material is human cardiac tissue, so this is a DIRECT match rather than a gene- or word-only hit. Title, sample count, and organism are GEO's own values. No evidence block: a bulk-generated dataset record carries provenance notes rather than a manufactured abstract quote."],"contexts":[{"id":"disorder:Cardiac_Sarcoidosis","name":"Cardiac Sarcoidosis","kind":"Disorder","source_path":"kb/disorders/Cardiac_Sarcoidosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cardiac_Sarcoidosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cardiac_Sarcoidosis.html#dataset-geo-gse205734"}],"context_names":["Cardiac Sarcoidosis"],"disease_names":["Cardiac Sarcoidosis"],"disease_name":"Cardiac Sarcoidosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cardiac_Sarcoidosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cardiac_Sarcoidosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cardiac_Sarcoidosis.html#dataset-geo-gse205734"]},{"id":"dataset:geo:gse205751","accession":"geo:GSE205751","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE205751","title":"Increased expression of LOC100506314 in T cells from patients with vitiligo and contributed to the pathogenesis of vitiligo","alternate_titles":[],"description":"The aim of this study was to investigate the differential expression of long non-coding RNAs (lncRNAs) in T cells from patients with vitiligo and their roles in the pathogenesis of vitiligo. The expression profiles of the RNA transcripts in T cells from three patients with vitiligo and three controls were conducted using microarray analysis. These aberrantly-expressed genes were further validated using T cells from 41 patients with vitiligo and 28 controls. The biologic function of the specific lncRNAs was investigated using transfection, RNA pull-down assay plus proteomic approach and Western blotting.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37731844"],"publication_contexts":[{"context_id":"disorder:Vitiligo","publication":"PMID:37731844"}],"publication":"PMID:37731844","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37731844","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Vitiligo (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Vitiligo","name":"Vitiligo","kind":"Disorder","source_path":"kb/disorders/Vitiligo.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Vitiligo.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Vitiligo.html#dataset-geo-gse205751"}],"context_names":["Vitiligo"],"disease_names":["Vitiligo"],"disease_name":"Vitiligo","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Vitiligo.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Vitiligo.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Vitiligo.html#dataset-geo-gse205751"]},{"id":"dataset:geo:gse205812","accession":"geo:GSE205812","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE205812","title":"RNA Sequencing and Bioinformatics Analysis of Differentially Expressed Genes in the Peripheral Serum of Ankylosing Spondylitis patients","alternate_titles":[],"description":"We randomly selected three serum samples each from an AS and a normal control (NC) group for high-throughput sequencing followed by using edgeR to find differentially expressed genes (DEGs). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome pathway analyses and gene set enrichment analysis (GSEA)were used to comprehensively analyze the possible functions and pathways involved with these DEGs. Protein–protein interaction (PPI) networks were constructed using the STRING database and Cytoscape. The modules and hub genes of these DEGs were identified using MCODE and CytoHubba plugins.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37254181"],"publication_contexts":[{"context_id":"disorder:Ankylosing_Spondylitis","publication":"PMID:37254181"}],"publication":"PMID:37254181","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37254181","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Ankylosing Spondylitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Ankylosing_Spondylitis","name":"Ankylosing Spondylitis","kind":"Disorder","source_path":"kb/disorders/Ankylosing_Spondylitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ankylosing_Spondylitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Ankylosing_Spondylitis.html#dataset-geo-gse205812"}],"context_names":["Ankylosing Spondylitis"],"disease_names":["Ankylosing Spondylitis"],"disease_name":"Ankylosing Spondylitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Ankylosing_Spondylitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ankylosing_Spondylitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Ankylosing_Spondylitis.html#dataset-geo-gse205812"]},{"id":"dataset:geo:gse205867","accession":"geo:GSE205867","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE205867","title":"transcriptional profiling of neutrophils in Behcet's Disease (BD).","alternate_titles":[],"description":"Behçet’s Disease (BD) is a chronic and systemic vasculitis with unknown etiology. Although BD is considered a condition linking both autoimmunity and autoinflammation, aberrant innate immunity has emerged in its significant pathogenetic role, among which neutrophils directly drive inflammation in BD. To investigate neutrophil aberrance in BD, we performed bulk RNA-sequencing on isolated peripheral neutrophils from 10 pairs of BD and sex- and age-matched healthy control (HCs).","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[20],"sample_count":20,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:36243348"],"publication_contexts":[{"context_id":"disorder:Behcets_Disease","publication":"PMID:36243348"}],"publication":"PMID:36243348","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36243348","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Behcet's Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Behcets_Disease","name":"Behcet's Disease","kind":"Disorder","source_path":"kb/disorders/Behcets_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Behcets_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Behcet's_Disease.html#dataset-geo-gse205867"}],"context_names":["Behcet's Disease"],"disease_names":["Behcet's Disease"],"disease_name":"Behcet's Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Behcets_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Behcets_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Behcet's_Disease.html#dataset-geo-gse205867"]},{"id":"dataset:geo:gse206448","accession":"geo:GSE206448","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE206448","title":"RNA-Seq analysis for giant cell tumour of the bone","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[10],"sample_count":10,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Bulk transcriptomes of human giant cell tumor of bone."],"contexts":[{"id":"disorder:Bone_Giant_Cell_Tumor","name":"Bone Giant Cell Tumor","kind":"Disorder","source_path":"kb/disorders/Bone_Giant_Cell_Tumor.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bone_Giant_Cell_Tumor.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Bone_Giant_Cell_Tumor.html#dataset-geo-gse206448"}],"context_names":["Bone Giant Cell Tumor"],"disease_names":["Bone Giant Cell Tumor"],"disease_name":"Bone Giant Cell Tumor","same_context_model_ids":["model:kb/disorders/Bone_Giant_Cell_Tumor.yaml:CRISPR-Cas9 H3.3 G34W-edited GCTB tumor-derived cells","model:kb/disorders/Bone_Giant_Cell_Tumor.yaml:Monocyte osteoclastogenesis co-culture with GCTB stromal cells","model:kb/disorders/Bone_Giant_Cell_Tumor.yaml:Patient-derived GCTB stromal cell culture"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Bone_Giant_Cell_Tumor.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bone_Giant_Cell_Tumor.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Bone_Giant_Cell_Tumor.html#dataset-geo-gse206448"]},{"id":"dataset:geo:gse206680","accession":"geo:GSE206680","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE206680","title":"RHINOVIRUS INFECTION OF THE AIRWAY EPITHELIUM ENHANCES MAST CELL IMMUNE RESPONSES VIA EPITHELIAL-DERIVED INTERFERONS","alternate_titles":[],"description":"Rationale: Mast cells (MCs) within the airway epithelium in asthma are closely related to airway dysfunction, but crosstalk between airway epithelial cells (AECs) and MCs in asthma remains incompletely understood. Human rhinovirus (HRV) infections are key triggers for asthma progression and AECs from individuals with asthma may have dysregulated anti-viral responses. Objectives: We utilize primary phenotyped AECs in an ex vivo coculture model system to examine crosstalk between AECs and MCs following epithelial HRV infection.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[123],"sample_count":123,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:36708815"],"publication_contexts":[{"context_id":"disorder:Rhinovirus_Infection","publication":"PMID:36708815"}],"publication":"PMID:36708815","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36708815","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Rhinovirus Infection (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Rhinovirus_Infection","name":"Rhinovirus Infection","kind":"Disorder","source_path":"kb/disorders/Rhinovirus_Infection.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rhinovirus_Infection.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Rhinovirus_Infection.html#dataset-geo-gse206680"}],"context_names":["Rhinovirus Infection"],"disease_names":["Rhinovirus Infection"],"disease_name":"Rhinovirus Infection","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Rhinovirus_Infection.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rhinovirus_Infection.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Rhinovirus_Infection.html#dataset-geo-gse206680"]},{"id":"dataset:geo:gse206719","accession":"geo:GSE206719","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE206719","title":"Multi-omic signatures of Chronic Beryllium Disease bronchoalveolar lavage cells relate to T cell function and innate immunity","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["MULTI_OMICS"],"data_type_labels":["Multi Omics"],"data_type_label":"Multi Omics","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[144],"sample_count":144,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:35972918"],"publication_contexts":[{"context_id":"disorder:Chronic_Beryllium_Disease","publication":"PMID:35972918"}],"publication":"PMID:35972918","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/35972918","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Chronic Beryllium Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Chronic_Beryllium_Disease","name":"Chronic Beryllium Disease","kind":"Disorder","source_path":"kb/disorders/Chronic_Beryllium_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Beryllium_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chronic_Beryllium_Disease.html#dataset-geo-gse206719"}],"context_names":["Chronic Beryllium Disease"],"disease_names":["Chronic Beryllium Disease"],"disease_name":"Chronic Beryllium Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chronic_Beryllium_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Beryllium_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chronic_Beryllium_Disease.html#dataset-geo-gse206719"]},{"id":"dataset:geo:gse207007","accession":"geo:GSE207007","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE207007","title":"RNA sequencing in POLG-iPSC derived brain cells","alternate_titles":[],"description":"Transcriptomic collection covering POLG patient-specific fibroblasts, iPSCs and differentiated neural cells. The Alpers organoid study deposited its bulk RNA-seq in this collection; the broader accession also includes other POLG genotypes and should not be treated as one homogeneous Alpers cohort.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:38385069"],"publication_contexts":[{"context_id":"disorder:Alpers-Huttenlocher_Syndrome","publication":"PMID:38385069"}],"publication":"PMID:38385069","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38385069","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE207007","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE207007","reference_title":"RNA sequencing in POLG-iPSC derived brain cells","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"including patient-specific fibroblasts, iPSCs and iPSCs-derived neural stem cells (NSCs), and astrocytes.","explanation":"Repository scope includes several cell types and broader POLG genotypes."}],"notes":["Verified through a generated per-record GEO cache. The organoid study used one successfully differentiated Alpers donor with two clones and unrelated controls; cell replicates do not increase the patient count."],"contexts":[{"id":"disorder:Alpers-Huttenlocher_Syndrome","name":"Alpers-Huttenlocher Syndrome","kind":"Disorder","source_path":"kb/disorders/Alpers-Huttenlocher_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alpers-Huttenlocher_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Alpers-Huttenlocher_Syndrome.html#dataset-geo-gse207007"}],"context_names":["Alpers-Huttenlocher Syndrome"],"disease_names":["Alpers-Huttenlocher Syndrome"],"disease_name":"Alpers-Huttenlocher Syndrome","same_context_model_ids":["model:kb/disorders/Alpers-Huttenlocher_Syndrome.yaml:A449T mouse embryonic fibroblast mtDNA recovery","model:kb/disorders/Alpers-Huttenlocher_Syndrome.yaml:Alpers cortical organoids with nicotinamide riboside","model:kb/disorders/Alpers-Huttenlocher_Syndrome.yaml:Alpers iPSC-derived neural stem cells","model:kb/disorders/Alpers-Huttenlocher_Syndrome.yaml:HeLa LONP1 and POLG2 knockdown","model:kb/disorders/Alpers-Huttenlocher_Syndrome.yaml:Reconstituted human and mouse polymerase gamma assays","model:kb/disorders/Alpers-Huttenlocher_Syndrome.yaml:Valproate exposure in primary muscle-cell cultures"],"candidate_model_ids":["model:kb/disorders/Alpers-Huttenlocher_Syndrome.yaml:Alpers cortical organoids with nicotinamide riboside","model:kb/disorders/Alpers-Huttenlocher_Syndrome.yaml:Alpers iPSC-derived neural stem cells"],"association_basis":"Same publication as a NAM (candidate)","nam_disease_context":"Same publication as a NAM (candidate)","source_paths":["kb/disorders/Alpers-Huttenlocher_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alpers-Huttenlocher_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Alpers-Huttenlocher_Syndrome.html#dataset-geo-gse207007"]},{"id":"dataset:geo:gse208171","accession":"geo:GSE208171","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE208171","title":"Loss of protein function of ZC4H2 gene causing severe phenotypes of female-restricted Wieacker Wolff Syndrome","alternate_titles":[],"description":"Background: Pathogenic variants of zinc finger C4H2-type containing (ZC4H2) on the X chromosome caused a group of genetic diseases called ZC4H2-associated rare disorders (ZARD), including Wieacker-Wolff Syndrome (WRWF) and Female-restricted Wieacker-Wolff Syndrome (WRWFFR). Patients displayed arthrogryposis multiplex congenita (AMC), central and peripheral nervous system involvement, as well as multiple dysmorphic features. The underlying mechanisms of the complex syndrome remain to be elucidated. Methods: Expression levels of ZC4H2 were knockdown in neural stem cells (NSCs) derived from induced pluripotent stem cells (iPSCs) by lentiviral-expressed shRNAs against ZC4H2.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Arthrogryposis Multiplex Congenita (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Arthrogryposis_Multiplex_Congenita","name":"Arthrogryposis Multiplex Congenita","kind":"Disorder","source_path":"kb/disorders/Arthrogryposis_Multiplex_Congenita.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Arthrogryposis_Multiplex_Congenita.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Arthrogryposis_Multiplex_Congenita.html#dataset-geo-gse208171"}],"context_names":["Arthrogryposis Multiplex Congenita"],"disease_names":["Arthrogryposis Multiplex Congenita"],"disease_name":"Arthrogryposis Multiplex Congenita","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Arthrogryposis_Multiplex_Congenita.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Arthrogryposis_Multiplex_Congenita.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Arthrogryposis_Multiplex_Congenita.html#dataset-geo-gse208171"]},{"id":"dataset:geo:gse208722","accession":"geo:GSE208722","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE208722","title":"Effect of MKRN3 deletion on gene expression in hypothalamic neurons derived from human induced pluripotent stem cells (hiPSCs)","alternate_titles":[],"description":"Makorin ring finger protein 3 (MKRN3) was identified as an inhibitor of puberty initiation with the report of loss-of-function mutations in association with central precocious puberty. To investigate the roles and mechanisms of action of MKRN3 within the human hypothalamus, we used hypothalamic neurons derived from human induced pluripotent stem cells (hiPSCs). MKRN3 deletion was introduced into hiPSCs using CRISPR interference (CRISPRi) technology. Three separated hypothalamic differentiation of MKRN3-wildtype hiPSCs (MKRN3-WT I, II and III) and MKRN3-deficient hiPSCs (MKRN3-KO I, II and III) were performed using an established hypothalamic neuron differentiation protocol.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37092553"],"publication_contexts":[{"context_id":"disorder:Central_Precocious_Puberty","publication":"PMID:37092553"}],"publication":"PMID:37092553","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37092553","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Central Precocious Puberty (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Central_Precocious_Puberty","name":"Central Precocious Puberty","kind":"Disorder","source_path":"kb/disorders/Central_Precocious_Puberty.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Central_Precocious_Puberty.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Central_Precocious_Puberty.html#dataset-geo-gse208722"}],"context_names":["Central Precocious Puberty"],"disease_names":["Central Precocious Puberty"],"disease_name":"Central Precocious Puberty","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Central_Precocious_Puberty.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Central_Precocious_Puberty.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Central_Precocious_Puberty.html#dataset-geo-gse208722"]},{"id":"dataset:geo:gse209838","accession":"geo:GSE209838","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE209838","title":"Plasma small-extracellular vesicles enriched in miR-122-5p promote disease aggressiveness in pediatric Anaplastic Large Cell Lymphoma","alternate_titles":[],"description":"Emerging evidence shows that small extracellular vesicles (S-EVs) play a critical role in cancer biology. However, the role of S-EVs in pediatric anaplastic large cell lymphoma (ALCL) is still largely unknown. Small RNA sequencing of plasma S-EVs revealed a peculiar microRNA profile in pediatric ALCL patients compared to healthy donors (HD). In particular, the liver-specific miR-122-5p was more abundant in ALCL plasma S-EVs compared to HD. Elevated levels of miR-122-5p correlated with advanced stage disease and impaired hepatic function in ALCL patients.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[50],"sample_count":50,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37014813"],"publication_contexts":[{"context_id":"disorder:Anaplastic_Large_Cell_Lymphoma","publication":"PMID:37014813"}],"publication":"PMID:37014813","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37014813","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Anaplastic Large Cell Lymphoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Anaplastic_Large_Cell_Lymphoma","name":"Anaplastic Large Cell Lymphoma","kind":"Disorder","source_path":"kb/disorders/Anaplastic_Large_Cell_Lymphoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Anaplastic_Large_Cell_Lymphoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Anaplastic_Large_Cell_Lymphoma.html#dataset-geo-gse209838"}],"context_names":["Anaplastic Large Cell Lymphoma"],"disease_names":["Anaplastic Large Cell Lymphoma"],"disease_name":"Anaplastic Large Cell Lymphoma","same_context_model_ids":["model:kb/disorders/Anaplastic_Large_Cell_Lymphoma.yaml:Dominant-Negative STAT3 in Karpas 299 and SU-DHL-1 Cells"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Anaplastic_Large_Cell_Lymphoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Anaplastic_Large_Cell_Lymphoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Anaplastic_Large_Cell_Lymphoma.html#dataset-geo-gse209838"]},{"id":"dataset:geo:gse21001","accession":"geo:GSE21001","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE21001","title":"Infection of MK2 cells with monkeypox virus","alternate_titles":[],"description":"Microarray analysis of MK2 (monkey kidney) cells infected with monkeypox virus at 3 and 7 hours post-infection to identify host genes essential for viral replication. Examines how orthopoxvirus alters host gene expression targeting immune responses.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9544","label":"Macaca mulatta","display_label":"rhesus macaque","url":"http://purl.obolibrary.org/obo/NCBITaxon_9544"}],"organism_labels":["Macaca mulatta"],"organism_label":"Macaca mulatta","sample_types":[{"id":"UBERON:0002113","label":"kidney","display_label":"kidney","url":"http://purl.obolibrary.org/obo/UBERON_0002113"}],"sample_type_labels":["kidney"],"sample_counts":[9],"sample_count":9,"conditions":["mock infected control","MPXV 3 hours post-infection","MPXV 7 hours post-infection"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["Affymetrix Rhesus Macaque Genome Array"],"platform":"Affymetrix Rhesus Macaque Genome Array","publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identifies host genes exploited for viral replication and humoral immune response targeting. Important for understanding early viral infection dynamics"],"contexts":[{"id":"disorder:Monkeypox","name":"Monkeypox","kind":"Disorder","source_path":"kb/disorders/Monkeypox.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Monkeypox.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Monkeypox.html#dataset-geo-gse21001"}],"context_names":["Monkeypox"],"disease_names":["Monkeypox"],"disease_name":"Monkeypox","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Monkeypox.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Monkeypox.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Monkeypox.html#dataset-geo-gse21001"]},{"id":"dataset:geo:gse210094","accession":"geo:GSE210094","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE210094","title":"The Role of FOXO4/NFAT2 Signaling Pathway in Dysfunction of Human Coronary Endothelial Cells and Inflammatory Infiltration of Vasculitis in Kawasaki Disease","alternate_titles":[],"description":"Aims: The Ca+/NFAT (Nuclear factor of activated T cells) signaling pathway activation is implicated in the pathogenesis of Kawasaki disease (KD); however, we lack detailed information regarding the regulatory network involved in the human coronary endothelial cell dysfunction and cardiovascular lesion development. Herein, we aimed to use mouse and endothelial cell models of KD vasculitis in vivo and in vitro to characterize the regulatory network of NFAT pathway in KD. Methods and Results: Among the NFAT gene family, NFAT2 showed the strongest transcriptional activity in peripheral blood mononuclear cells (PBMCs) from patients with KD.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[16],"sample_count":16,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:36700213"],"publication_contexts":[{"context_id":"disorder:Kawasaki_Disease","publication":"PMID:36700213"}],"publication":"PMID:36700213","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36700213","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Kawasaki Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Kawasaki_Disease","name":"Kawasaki Disease","kind":"Disorder","source_path":"kb/disorders/Kawasaki_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Kawasaki_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Kawasaki_Disease.html#dataset-geo-gse210094"}],"context_names":["Kawasaki Disease"],"disease_names":["Kawasaki Disease"],"disease_name":"Kawasaki Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Kawasaki_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Kawasaki_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Kawasaki_Disease.html#dataset-geo-gse210094"]},{"id":"dataset:geo:gse210484","accession":"geo:GSE210484","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE210484","title":"DNA methylation profiling of Arboleda-Tham syndrome in primary human fibroblasts","alternate_titles":[],"description":"Arboleda-Tham Syndrome is a rare disease caused by de novo mutations in the KAT6A gene. Epigenetic changes to the genome resulting from pathogenic mutations were investigated by DNAme profiling.","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[25],"sample_count":25,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:36064314"],"publication_contexts":[{"context_id":"disorder:Arboleda-Tham_Syndrome","publication":"PMID:36064314"}],"publication":"PMID:36064314","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36064314","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Arboleda-Tham Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Arboleda-Tham_Syndrome","name":"Arboleda-Tham Syndrome","kind":"Disorder","source_path":"kb/disorders/Arboleda-Tham_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Arboleda-Tham_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Arboleda-Tham_Syndrome.html#dataset-geo-gse210484"}],"context_names":["Arboleda-Tham Syndrome"],"disease_names":["Arboleda-Tham Syndrome"],"disease_name":"Arboleda-Tham Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Arboleda-Tham_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Arboleda-Tham_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Arboleda-Tham_Syndrome.html#dataset-geo-gse210484"]},{"id":"dataset:geo:gse210600","accession":"geo:GSE210600","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE210600","title":"Interleukin-17 drives sex-dependent weight loss and changes in feeding behaviour during Trypanosoma brucei infection","alternate_titles":[],"description":"African trypanosomes, the causative agents of Human and Animal African trypanosomiasis or sleeping sickness, reside in tissue niches proposed to be important for disease outcome and transmission. Here, we demonstrate that parasites in the inguinal white adipose tissue (iWAT) niche induce sexually dimorphic physiological and immunological responses. Following chronic Trypanosoma brucei infection, male mice experience weight loss, reduced adipose tissue mass and altered tissue function, as well as changes in feeding behaviour, whereas females do not.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[16],"sample_count":16,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37923768"],"publication_contexts":[{"context_id":"disorder:Human_African_Trypanosomiasis","publication":"PMID:37923768"}],"publication":"PMID:37923768","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37923768","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Human African trypanosomiasis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Human_African_Trypanosomiasis","name":"Human African trypanosomiasis","kind":"Disorder","source_path":"kb/disorders/Human_African_Trypanosomiasis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Human_African_Trypanosomiasis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Human_African_trypanosomiasis.html#dataset-geo-gse210600"}],"context_names":["Human African trypanosomiasis"],"disease_names":["Human African trypanosomiasis"],"disease_name":"Human African trypanosomiasis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Human_African_Trypanosomiasis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Human_African_Trypanosomiasis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Human_African_trypanosomiasis.html#dataset-geo-gse210600"]},{"id":"dataset:geo:gse211225","accession":"geo:GSE211225","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE211225","title":"Altered Cellular Pathways in the Blood of Patients With Guillain-Barre Syndrome","alternate_titles":[],"description":"Background and aims: Guillain-Barré syndrome (GBS) is a rare disorder, with a global incidence ranging from 1 to 2 individuals per 100,000 people/year. Infections and vaccines have been implicated as causes triggering GBS. The aim of the study was to identify host genes involved in the pathogenesis of GBS when Zika (ZIKV) and Chikungunya viruses (CHIKV) were introduced in Brazil. Methods: A case-control study of GBS was performed when ZIKV and CHIKV were introduced into a naïve population. GBS was studied during both acute and postacute phases. RNA sequencing was conducted using whole blood.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[22],"sample_count":22,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40099626"],"publication_contexts":[{"context_id":"disorder:Guillain_Barre_Syndrome","publication":"PMID:40099626"}],"publication":"PMID:40099626","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40099626","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Guillain-Barre Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Guillain_Barre_Syndrome","name":"Guillain-Barre Syndrome","kind":"Disorder","source_path":"kb/disorders/Guillain_Barre_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Guillain_Barre_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Guillain-Barre_Syndrome.html#dataset-geo-gse211225"}],"context_names":["Guillain-Barre Syndrome"],"disease_names":["Guillain-Barre Syndrome"],"disease_name":"Guillain-Barre Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Guillain_Barre_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Guillain_Barre_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Guillain-Barre_Syndrome.html#dataset-geo-gse211225"]},{"id":"dataset:geo:gse211990","accession":"geo:GSE211990","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE211990","title":"A kinase-independent function of cyclin-dependent kinase 6 promotes outer radial glia expansion and neocortical folding","alternate_titles":[],"description":"Mouse cortical RNA-sequencing resource used to study CDK6-dependent outer-radial-glia expansion and neocortical folding.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[19],"sample_count":19,"conditions":["Cdk6-deficient experimental cortex","Matched control cortex"],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:1777","label":"CDK6","display_label":"CDK6","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/1777"}],"genes":["CDK6"],"platforms":[],"platform":null,"publications":["PMID:36095192"],"publication_contexts":[{"context_id":"disorder:Autosomal_Recessive_Primary_Microcephaly","publication":"PMID:36095192"}],"publication":"PMID:36095192","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36095192","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:36095192","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/36095192","reference_title":"A kinase-independent function of cyclin-dependent kinase 6 promotes outer radial glia expansion and neocortical folding.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"CDK6 loss selectively decreased oRGs and abolished neocortical folding.","explanation":"The associated publication supports the CDK6 cortical model and its key phenotype."}],"notes":[],"contexts":[{"id":"disorder:Autosomal_Recessive_Primary_Microcephaly","name":"Autosomal Recessive Primary Microcephaly","kind":"Disorder","source_path":"kb/disorders/Autosomal_Recessive_Primary_Microcephaly.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autosomal_Recessive_Primary_Microcephaly.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Recessive_Primary_Microcephaly.html#dataset-geo-gse211990"}],"context_names":["Autosomal Recessive Primary Microcephaly"],"disease_names":["Autosomal Recessive Primary Microcephaly"],"disease_name":"Autosomal Recessive Primary Microcephaly","same_context_model_ids":["model:kb/disorders/Autosomal_Recessive_Primary_Microcephaly.yaml:CDK5RAP2 patient-derived high-quantity brain organoids","model:kb/disorders/Autosomal_Recessive_Primary_Microcephaly.yaml:CETN3-knockout human cerebral organoids","model:kb/disorders/Autosomal_Recessive_Primary_Microcephaly.yaml:CIT kinase-dead and frameshift human forebrain organoids","model:kb/disorders/Autosomal_Recessive_Primary_Microcephaly.yaml:WDR62 patient-derived neural progenitor and cerebral organoid models"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Autosomal_Recessive_Primary_Microcephaly.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autosomal_Recessive_Primary_Microcephaly.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Recessive_Primary_Microcephaly.html#dataset-geo-gse211990"]},{"id":"dataset:geo:gse212105","accession":"geo:GSE212105","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE212105","title":"Coxsackievirus A10 impairs nail regeneration and induces onychomadesis by mimicking DKK1 to attenuate Wnt signaling","alternate_titles":[],"description":"Transcriptomic study of CV-A10-induced nail matrix damage in a mouse model, elucidating the mechanism of post-HFMD onychomadesis.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:38836810","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38836810","reference_title":"Coxsackievirus A10 impairs nail regeneration and induces onychomadesis by mimicking DKK1 to attenuate Wnt signaling.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"Here, we found that CV-A10 infection in mice could suppress Wnt/β-catenin signaling by restraining LDL receptor-related protein 6 (LRP6) phosphorylation and β-catenin accumulation and lead to onychomadesis.","explanation":"Supports this dataset as a mouse transcriptomic/modeling resource for CV-A10-associated onychomadesis after HFMD."}],"notes":[],"contexts":[{"id":"disorder:Hand_Foot_and_Mouth_Disease","name":"Hand Foot and Mouth Disease","kind":"Disorder","source_path":"kb/disorders/Hand_Foot_and_Mouth_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hand_Foot_and_Mouth_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hand_Foot_and_Mouth_Disease.html#dataset-geo-gse212105"}],"context_names":["Hand Foot and Mouth Disease"],"disease_names":["Hand Foot and Mouth Disease"],"disease_name":"Hand Foot and Mouth Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hand_Foot_and_Mouth_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hand_Foot_and_Mouth_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hand_Foot_and_Mouth_Disease.html#dataset-geo-gse212105"]},{"id":"dataset:geo:gse212296","accession":"geo:GSE212296","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE212296","title":"Genome-wide analysis of copy number variation in humans with cleft lip and/or cleft palate identifies COBLL1, RIC1, and ARHGEF38 as clefting genes","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[1108],"sample_count":1108,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:36493769"],"publication_contexts":[{"context_id":"disorder:Cleft_Lip_Palate","publication":"PMID:36493769"}],"publication":"PMID:36493769","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36493769","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Cleft Lip/Palate (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Cleft_Lip_Palate","name":"Cleft Lip/Palate","kind":"Disorder","source_path":"kb/disorders/Cleft_Lip_Palate.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cleft_Lip_Palate.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cleft_Lip_Palate.html#dataset-geo-gse212296"}],"context_names":["Cleft Lip/Palate"],"disease_names":["Cleft Lip/Palate"],"disease_name":"Cleft Lip/Palate","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cleft_Lip_Palate.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cleft_Lip_Palate.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cleft_Lip_Palate.html#dataset-geo-gse212296"]},{"id":"dataset:geo:gse212610","accession":"geo:GSE212610","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE212610","title":"Integrated genomic, transcriptomic and metabolomic analysis reveals MDH2 mutation-induced metabolic disorder in recurrent focal segmental glomerulosclerosis","alternate_titles":[],"description":"Focal segmental glomerulosclerosis (FSGS) has an over 30% risk of recurrence after kidney transplantation (Ktx) and is associated with an extremely high risk of graft loss. However, mechanisms remain largely unclear. Thus, this study identifies novel genes related to the recurrence of FSGS (rFSGS). Whole genome-wide sequencing and next-generation RNA sequencing were used to identify the candidate mutant genes associated with rFSGS in peripheral blood mononuclear cells (PBMCs) from patients with biopsy-confirmed rFSGS after KTx.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[9],"sample_count":9,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:36159820"],"publication_contexts":[{"context_id":"disorder:Focal_Segmental_Glomerulosclerosis","publication":"PMID:36159820"}],"publication":"PMID:36159820","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36159820","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Focal Segmental Glomerulosclerosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Focal_Segmental_Glomerulosclerosis","name":"Focal Segmental Glomerulosclerosis","kind":"Disorder","source_path":"kb/disorders/Focal_Segmental_Glomerulosclerosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Focal_Segmental_Glomerulosclerosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Focal_Segmental_Glomerulosclerosis.html#dataset-geo-gse212610"}],"context_names":["Focal Segmental Glomerulosclerosis"],"disease_names":["Focal Segmental Glomerulosclerosis"],"disease_name":"Focal Segmental Glomerulosclerosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Focal_Segmental_Glomerulosclerosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Focal_Segmental_Glomerulosclerosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Focal_Segmental_Glomerulosclerosis.html#dataset-geo-gse212610"]},{"id":"dataset:geo:gse212983","accession":"geo:GSE212983","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE212983","title":"Hippocampus-specific loss of intellectual disability-related gene Brpf1 impaired spatial and contextual learning","alternate_titles":[],"description":"RNA-seq of hippocampal CA1 tissue from postnatal CaMKIIa-Cre Brpf1 conditional knockout and control mice.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"Mus musculus","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[8],"sample_count":8,"conditions":["Control hippocampal CA1 tissue","CaMKIIa-Cre Brpf1 conditional knockout hippocampal CA1 tissue"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["Illumina NovaSeq 6000 (GPL24247)"],"platform":"Illumina NovaSeq 6000 (GPL24247)","publications":["PMID:37862219"],"publication_contexts":[{"context_id":"disorder:BRPF1-Related_Intellectual_Disability","publication":"PMID:37862219"}],"publication":"PMID:37862219","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37862219","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Four samples per group from two-month-old males. Bulk tissue and nominal DEG thresholds limit cell-specific and causal interpretation."],"contexts":[{"id":"disorder:BRPF1-Related_Intellectual_Disability","name":"BRPF1-Related Intellectual Disability","kind":"Disorder","source_path":"kb/disorders/BRPF1-Related_Intellectual_Disability.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/BRPF1-Related_Intellectual_Disability.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/BRPF1-Related_Intellectual_Disability.html#dataset-geo-gse212983"}],"context_names":["BRPF1-Related Intellectual Disability"],"disease_names":["BRPF1-Related Intellectual Disability"],"disease_name":"BRPF1-Related Intellectual Disability","same_context_model_ids":["model:kb/disorders/BRPF1-Related_Intellectual_Disability.yaml:BRPF1 Pro370Ser patient-derived lymphoblastoid cells","model:kb/disorders/BRPF1-Related_Intellectual_Disability.yaml:Brpf1-knockdown mouse hippocampal neuron cultures","model:kb/disorders/BRPF1-Related_Intellectual_Disability.yaml:Brpf1-knockdown mouse MGE-derived interneuron cultures","model:kb/disorders/BRPF1-Related_Intellectual_Disability.yaml:Brpf1-null fetal-liver and neonatal marrow colony cultures","model:kb/disorders/BRPF1-Related_Intellectual_Disability.yaml:BRPF1-null human H1 embryonic stem cells with inducible rescue","model:kb/disorders/BRPF1-Related_Intellectual_Disability.yaml:Emx1-lineage Brpf1 conditional cortical neuron cultures","model:kb/disorders/BRPF1-Related_Intellectual_Disability.yaml:Inducible Brpf1-null mouse embryonic fibroblasts"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/BRPF1-Related_Intellectual_Disability.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/BRPF1-Related_Intellectual_Disability.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/BRPF1-Related_Intellectual_Disability.html#dataset-geo-gse212983"]},{"id":"dataset:geo:gse213030","accession":"geo:GSE213030","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE213030","title":"Tumor necrosis factor activation variability in minimal change disease and focal segmental glomerulosclerosis: a model for precision nephrology","alternate_titles":[],"description":"Reporter genes for TNF activation have not been studied in nephrotic syndrome cases at the single nuclear RNA-seq level. Use of archived kidney biopsy material that was fragmented into individual nuclei and assayed for presence of genes involved in TNF activation in patients predicted to have high or low expression of these genes.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[10],"sample_count":10,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:36442540"],"publication_contexts":[{"context_id":"disorder:Focal_Segmental_Glomerulosclerosis","publication":"PMID:36442540"}],"publication":"PMID:36442540","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36442540","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Focal Segmental Glomerulosclerosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Focal_Segmental_Glomerulosclerosis","name":"Focal Segmental Glomerulosclerosis","kind":"Disorder","source_path":"kb/disorders/Focal_Segmental_Glomerulosclerosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Focal_Segmental_Glomerulosclerosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Focal_Segmental_Glomerulosclerosis.html#dataset-geo-gse213030"}],"context_names":["Focal Segmental Glomerulosclerosis"],"disease_names":["Focal Segmental Glomerulosclerosis"],"disease_name":"Focal Segmental Glomerulosclerosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Focal_Segmental_Glomerulosclerosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Focal_Segmental_Glomerulosclerosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Focal_Segmental_Glomerulosclerosis.html#dataset-geo-gse213030"]},{"id":"dataset:geo:gse213332","accession":"geo:GSE213332","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE213332","title":"Timecourse CAGE analysis of Madurella mycetomatis grain development in Galleria mellonella","alternate_titles":[],"description":"Mycetoma is a neglected, chronic granulomatous infection of the subcutaneous tissue, most often caused by the fungal pathogen Madurella mycetomatis. Characteristic of the infection is the formation of grains. However, knowledge of the function and formation of the grain is limited. To map the processes leading to M. mycetomatis grain formation, we used a Galleria mellonella larvae infection model and time-course transcriptomic profiling. In the infected G. mellonella 88.0% of the RNA sequence reads mapped to G. mellonella, only 0.01% mapped to M. mycetomatis. Differential Gene Expression analysis revealed that 3.498 G. mellonella and 137 M.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[15],"sample_count":15,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40562743"],"publication_contexts":[{"context_id":"disorder:Mycetoma","publication":"PMID:40562743"}],"publication":"PMID:40562743","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40562743","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Mycetoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Mycetoma","name":"Mycetoma","kind":"Disorder","source_path":"kb/disorders/Mycetoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mycetoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Mycetoma.html#dataset-geo-gse213332"}],"context_names":["Mycetoma"],"disease_names":["Mycetoma"],"disease_name":"Mycetoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Mycetoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mycetoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Mycetoma.html#dataset-geo-gse213332"]},{"id":"dataset:geo:gse213364","accession":"geo:GSE213364","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE213364","title":"Molecular and spatial heterogeneity of microglia in Rasmussen encephalitis","alternate_titles":[],"description":"Rasmussen encephalitis (RE) is a rare childhood neurological disease characterized by progressive unilateral loss of function, hemispheric atrophy and drug-resistant epilepsy. Affected brain tissue shows signs of infiltrating cytotoxic T-cells, microglial activation, and neuronal death, implicating an inflammatory disease process. Recent studies have identified molecular correlates of inflammation in RE, but cell-type-specific mechanisms remain unclear. We used single-nucleus RNA-sequencing (snRNA-seq) to assess gene expression across multiple cell types in brain tissue resected from two children with RE.","alternate_descriptions":[],"data_types":["MULTI_OMICS"],"data_type_labels":["Multi Omics"],"data_type_label":"Multi Omics","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:36411471"],"publication_contexts":[{"context_id":"disorder:Rasmussen_Encephalitis","publication":"PMID:36411471"}],"publication":"PMID:36411471","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36411471","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Rasmussen Encephalitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Rasmussen_Encephalitis","name":"Rasmussen Encephalitis","kind":"Disorder","source_path":"kb/disorders/Rasmussen_Encephalitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rasmussen_Encephalitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Rasmussen_Encephalitis.html#dataset-geo-gse213364"}],"context_names":["Rasmussen Encephalitis"],"disease_names":["Rasmussen Encephalitis"],"disease_name":"Rasmussen Encephalitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Rasmussen_Encephalitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rasmussen_Encephalitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Rasmussen_Encephalitis.html#dataset-geo-gse213364"]},{"id":"dataset:geo:gse213589","accession":"geo:GSE213589","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE213589","title":"Transcriptomic alterations of thallium-exposed zebrafish embryos","alternate_titles":[],"description":"Bulk RNA-seq toxicogenomic dataset profiling wild-type zebrafish embryos exposed to graded thallium concentrations during early development, useful for studying developmental and stress-response programs perturbed by thallium.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:7955","label":"Danio rerio","display_label":"zebrafish","url":"http://purl.obolibrary.org/obo/NCBITaxon_7955"}],"organism_labels":["Danio rerio"],"organism_label":"Danio rerio","sample_types":[],"sample_type_labels":[],"sample_counts":[10],"sample_count":10,"conditions":["wild-type zebrafish embryos exposed to 0 ppb thallium","wild-type zebrafish embryos exposed to 200 ppb thallium","wild-type zebrafish embryos exposed to 800 ppb thallium"],"exposure_terms":[{"id":"ECTO:9001312","label":"exposure to thallium","display_label":"exposure to thallium","url":"http://purl.obolibrary.org/obo/ECTO_9001312"}],"exposures":["exposure to thallium"],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:36403832"],"publication_contexts":[{"context_id":"disorder:Thallium_Poisoning","publication":"PMID:36403832"}],"publication":"PMID:36403832","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36403832","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE213589","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE213589","reference_title":"Transcriptomic alterations of thallium-exposed zebrafish embryos","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"Thallium (Tl) is a trace metal element used in the electronics, semiconductor and electro-optical industries. With the development of high-tech industries, thallium severely pollutes the aquatic environment. The purpose of this study was to evaluate the cardiotoxicity and developmental toxicity of Tl by using vertebrate model zebrafish embryos. RNA-seq was performed on wild type zebrafish embryos exposed to 0, 200, and 800 ppb Tl from 6 to 48 hpf. The transcriptomic profile revealed molecular understanding regarding the cardiovascular and developmental toxicity of Tl, providing valuable information for risk assessment of the emerging contaminant thallium.","explanation":"Supports this GEO series as a model-organism bulk RNA-seq resource directly profiling transcriptomic responses to graded thallium exposure."}],"notes":["Dataset record: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE213589. Useful as a mechanistic toxicogenomic resource rather than a human clinical cohort."],"contexts":[{"id":"disorder:Thallium_Poisoning","name":"Thallium Poisoning","kind":"Disorder","source_path":"kb/disorders/Thallium_Poisoning.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Thallium_Poisoning.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Thallium_Poisoning.html#dataset-geo-gse213589"}],"context_names":["Thallium Poisoning"],"disease_names":["Thallium Poisoning"],"disease_name":"Thallium Poisoning","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Thallium_Poisoning.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Thallium_Poisoning.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Thallium_Poisoning.html#dataset-geo-gse213589"]},{"id":"dataset:geo:gse213695","accession":"geo:GSE213695","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE213695","title":"BRPF1 co-occupies with H3K4me3 and H3K23ac in human ESCs essential to pluripotency","alternate_titles":[],"description":"SuperSeries containing transcriptomic, chromatin accessibility and occupancy profiling of engineered H1 embryonic stem cells.","alternate_descriptions":[],"data_types":["MULTI_OMICS_PERTURBATION"],"data_type_labels":["Multi Omics Perturbation"],"data_type_label":"Multi Omics Perturbation","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"Homo sapiens","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[18],"sample_count":18,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["Illumina NovaSeq 6000 (GPL24676; GEO record)"],"platform":"Illumina NovaSeq 6000 (GPL24676; GEO record)","publications":["PMID:36711238"],"publication_contexts":[{"context_id":"disorder:BRPF1-Related_Intellectual_Disability","publication":"PMID:36711238"}],"publication":"PMID:36711238","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36711238","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["The total counts deposited samples across assays, not independent patients or eighteen biological donors. The study also deposits data under HRA001928. Complete engineered loss, differentiation state and assay-specific controls must be considered when using the data. GEO assigns platform GPL24676 (NovaSeq 6000), while the paper methods describe NextSeq 500 sequencing; this source discrepancy should be checked before platform-specific reanalysis. SubSeries are GSE213690, GSE213692 and GSE213694."],"contexts":[{"id":"disorder:BRPF1-Related_Intellectual_Disability","name":"BRPF1-Related Intellectual Disability","kind":"Disorder","source_path":"kb/disorders/BRPF1-Related_Intellectual_Disability.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/BRPF1-Related_Intellectual_Disability.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/BRPF1-Related_Intellectual_Disability.html#dataset-geo-gse213695"}],"context_names":["BRPF1-Related Intellectual Disability"],"disease_names":["BRPF1-Related Intellectual Disability"],"disease_name":"BRPF1-Related Intellectual Disability","same_context_model_ids":["model:kb/disorders/BRPF1-Related_Intellectual_Disability.yaml:BRPF1 Pro370Ser patient-derived lymphoblastoid cells","model:kb/disorders/BRPF1-Related_Intellectual_Disability.yaml:Brpf1-knockdown mouse hippocampal neuron cultures","model:kb/disorders/BRPF1-Related_Intellectual_Disability.yaml:Brpf1-knockdown mouse MGE-derived interneuron cultures","model:kb/disorders/BRPF1-Related_Intellectual_Disability.yaml:Brpf1-null fetal-liver and neonatal marrow colony cultures","model:kb/disorders/BRPF1-Related_Intellectual_Disability.yaml:BRPF1-null human H1 embryonic stem cells with inducible rescue","model:kb/disorders/BRPF1-Related_Intellectual_Disability.yaml:Emx1-lineage Brpf1 conditional cortical neuron cultures","model:kb/disorders/BRPF1-Related_Intellectual_Disability.yaml:Inducible Brpf1-null mouse embryonic fibroblasts"],"candidate_model_ids":["model:kb/disorders/BRPF1-Related_Intellectual_Disability.yaml:BRPF1-null human H1 embryonic stem cells with inducible rescue"],"association_basis":"Same publication as a NAM (candidate)","nam_disease_context":"Same publication as a NAM (candidate)","source_paths":["kb/disorders/BRPF1-Related_Intellectual_Disability.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/BRPF1-Related_Intellectual_Disability.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/BRPF1-Related_Intellectual_Disability.html#dataset-geo-gse213695"]},{"id":"dataset:geo:gse213798","accession":"geo:GSE213798","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE213798","title":"Aberrant cortical layer development of brain organoids developed from Noonan syndrome-iPSCs","alternate_titles":[],"description":"Human induced pluripotent stem cell-derived cortical organoid transcriptomic resource profiling neurodevelopmental abnormalities in Noonan syndrome and matched isogenic corrected controls across developmental time points.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[9],"sample_count":9,"conditions":["Noonan syndrome iPSC-derived cortical organoids","isogenic corrected control cortical organoids"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["GPL24676"],"platform":"GPL24676","publications":["GEO:GSE213798"],"publication_contexts":[{"context_id":"disorder:Noonan_Syndrome","publication":"GEO:GSE213798"}],"publication":"GEO:GSE213798","publication_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE213798","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE213798","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE213798","reference_title":"Aberrant cortical layer development of brain organoids developed from Noonan syndrome-iPSCs","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"single-cell transcriptomic analysis represented increment of EN population and overexpression of cortical layer markers in NS-COs.","explanation":"Provides disease-relevant human neurodevelopmental transcriptomic evidence for cortical-layer and neuronal-connectivity abnormalities in Noonan syndrome."}],"notes":[],"contexts":[{"id":"disorder:Noonan_Syndrome","name":"Noonan Syndrome","kind":"Disorder","source_path":"kb/disorders/Noonan_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Noonan_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Noonan_Syndrome.html#dataset-geo-gse213798"}],"context_names":["Noonan Syndrome"],"disease_names":["Noonan Syndrome"],"disease_name":"Noonan Syndrome","same_context_model_ids":["model:kb/disorders/Noonan_Syndrome.yaml:Noonan syndrome cortical organoid model","model:kb/disorders/Noonan_Syndrome.yaml:Noonan syndrome iPSC-cardiomyocyte model"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Noonan_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Noonan_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Noonan_Syndrome.html#dataset-geo-gse213798"]},{"id":"dataset:geo:gse213907","accession":"geo:GSE213907","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE213907","title":"EXPLORING GENE EXPRESSION PROFILES IN PRIMARY CENTRAL NERVOUS SYSTEM VASCULITIS","alternate_titles":[],"description":"Bulk RNA sequencing of brain specimens from primary CNS vasculitis and controls, associated with Salvarani et al. (PMID:36264136).","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[17],"sample_count":17,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["The 17 specimens comprise four granulomatous vasculitis cases, five lymphocytic vasculitis cases, four amyloid-beta-related angiitis cases, and four controls. Pathway and immune-cell deconvolution analyses are exploratory; the dataset is not a functional perturbation experiment."],"contexts":[{"id":"disorder:CNS_Vasculitis","name":"CNS Vasculitis","kind":"Disorder","source_path":"kb/disorders/CNS_Vasculitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/CNS_Vasculitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/CNS_Vasculitis.html#dataset-geo-gse213907"}],"context_names":["CNS Vasculitis"],"disease_names":["CNS Vasculitis"],"disease_name":"CNS Vasculitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/CNS_Vasculitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/CNS_Vasculitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/CNS_Vasculitis.html#dataset-geo-gse213907"]},{"id":"dataset:geo:gse214745","accession":"geo:GSE214745","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE214745","title":"Transcriptomic insights into the role of the spleen in a mouse model of Wiskott-Aldrich Syndrome","alternate_titles":[],"description":"Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency characterized by microthrombocytopenia, eczema, recurrent infections, and increased incidence of autoimmune disorders and malignancies. WAS is caused by mutations in the was gene, which is expressed exclusively in hematopoietic cells, and the spleen plays an important role in hematopoiesis and red blood cell clearance. However, to date, detailed comparative analyses of the spleen between WASp-deficient (WAS-KO) mice and WT mice, particularly at the transcriptomic level, have not been reported. Here, we investigated the differences in the transcriptomes of spleen tissues of 10-week-old WAS-KO mice.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:36605531"],"publication_contexts":[{"context_id":"disorder:Wiskott_Aldrich_Syndrome","publication":"PMID:36605531"}],"publication":"PMID:36605531","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36605531","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Wiskott-Aldrich syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Wiskott_Aldrich_Syndrome","name":"Wiskott-Aldrich syndrome","kind":"Disorder","source_path":"kb/disorders/Wiskott_Aldrich_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Wiskott_Aldrich_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Wiskott-Aldrich_syndrome.html#dataset-geo-gse214745"}],"context_names":["Wiskott-Aldrich syndrome"],"disease_names":["Wiskott-Aldrich syndrome"],"disease_name":"Wiskott-Aldrich syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Wiskott_Aldrich_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Wiskott_Aldrich_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Wiskott-Aldrich_syndrome.html#dataset-geo-gse214745"]},{"id":"dataset:geo:gse215304","accession":"geo:GSE215304","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE215304","title":"Alpha kinase 3 signaling at the M-band maintains sarcomere integrity and proteostasis in striated muscle","alternate_titles":[],"description":"Transcriptomic profiling accompanying the study that localized ALPK3 to the sarcomeric M-band and defined the ALPK3-dependent phosphoproteome, using human pluripotent stem cell-derived cardiomyocytes carrying cardiomyopathic ALPK3 mutations.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[16],"sample_count":16,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39196058"],"publication_contexts":[{"context_id":"disorder:ALPK3-Related_Hypertrophic_Cardiomyopathy","publication":"PMID:39196058"}],"publication":"PMID:39196058","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39196058","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["ALPK3-mutant human cardiomyocyte RNA sequencing accompanying PMID:39196058; interpretation is specific to the edited cellular system rather than a patient myocardial cohort."],"contexts":[{"id":"disorder:ALPK3-Related_Hypertrophic_Cardiomyopathy","name":"ALPK3-Related Hypertrophic Cardiomyopathy","kind":"Disorder","source_path":"kb/disorders/ALPK3-Related_Hypertrophic_Cardiomyopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/ALPK3-Related_Hypertrophic_Cardiomyopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/ALPK3-Related_Hypertrophic_Cardiomyopathy.html#dataset-geo-gse215304"}],"context_names":["ALPK3-Related Hypertrophic Cardiomyopathy"],"disease_names":["ALPK3-Related Hypertrophic Cardiomyopathy"],"disease_name":"ALPK3-Related Hypertrophic Cardiomyopathy","same_context_model_ids":["model:kb/disorders/ALPK3-Related_Hypertrophic_Cardiomyopathy.yaml:ALPK3-deficient human cardiac organoids","model:kb/disorders/ALPK3-Related_Hypertrophic_Cardiomyopathy.yaml:ALPK3-null human stem cell-derived cardiomyocytes","model:kb/disorders/ALPK3-Related_Hypertrophic_Cardiomyopathy.yaml:Isogenic ALPK3 iPSC-derived cardiomyocytes for M-band proteomics"],"candidate_model_ids":["model:kb/disorders/ALPK3-Related_Hypertrophic_Cardiomyopathy.yaml:ALPK3-deficient human cardiac organoids"],"association_basis":"Same publication as a NAM (candidate)","nam_disease_context":"Same publication as a NAM (candidate)","source_paths":["kb/disorders/ALPK3-Related_Hypertrophic_Cardiomyopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/ALPK3-Related_Hypertrophic_Cardiomyopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/ALPK3-Related_Hypertrophic_Cardiomyopathy.html#dataset-geo-gse215304"]},{"id":"dataset:geo:gse215362","accession":"geo:GSE215362","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE215362","title":"Dual developmental effects of ARX poly-alanine mutations in human cortical excitatory and inhibitory neurons","alternate_titles":[],"description":"Infantile spasms (IS), a severe childhood epilepsy with an incidence of 1.6–4.5 per 10,000 live births, often lead to lifelong intellectual disability. Up to 5% of affected males carry mutations in the Aristaless-related homeobox (ARX) gene. The lack of human-specific models for developmental epilepsy limits progress, making organoids a promising alternative. We use human cortical (CO) and ganglionic eminence organoids (GEO) to model poly-alanine expansion (PAE) mutations in ARX. PAE mutations increase cortical progenitor proliferation and accelerate early cortical development.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[24],"sample_count":24,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41422506"],"publication_contexts":[{"context_id":"disorder:Infantile_Spasms","publication":"PMID:41422506"}],"publication":"PMID:41422506","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41422506","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Infantile Spasms (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Infantile_Spasms","name":"Infantile Spasms","kind":"Disorder","source_path":"kb/disorders/Infantile_Spasms.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Infantile_Spasms.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Infantile_Spasms.html#dataset-geo-gse215362"}],"context_names":["Infantile Spasms"],"disease_names":["Infantile Spasms"],"disease_name":"Infantile Spasms","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Infantile_Spasms.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Infantile_Spasms.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Infantile_Spasms.html#dataset-geo-gse215362"]},{"id":"dataset:geo:gse215457","accession":"geo:GSE215457","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE215457","title":"Inhibition of DYRK1B suppresses inflammation in allergic contact dermatitis model and Th1/Th17 immune response","alternate_titles":[],"description":"Transcriptomic dataset associated with DYRK1B inhibition experiments used to interrogate T-cell inflammatory programs relevant to allergic contact dermatitis and Th1/Th17 polarization.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"Homo sapiens","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE215457","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE215457","reference_title":"Inhibition of DYRK1B suppresses inflammation in allergic contact dermatitis model and Th1/Th17 immune response","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"To investigate the inhibition effect of DYRK1B kinase function on human naïve CD4+ T cell differetionation which stimulated under Treg polarizing condition for 24 hours.","explanation":"This GEO record supports a human T-cell transcriptomic dataset tied to mechanistic allergic contact dermatitis work on inflammatory T-cell polarization."}],"notes":["Dataset record: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE215457"],"contexts":[{"id":"disorder:Contact_Dermatitis","name":"Contact Dermatitis","kind":"Disorder","source_path":"kb/disorders/Contact_Dermatitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Contact_Dermatitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Contact_Dermatitis.html#dataset-geo-gse215457"}],"context_names":["Contact Dermatitis"],"disease_names":["Contact Dermatitis"],"disease_name":"Contact Dermatitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Contact_Dermatitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Contact_Dermatitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Contact_Dermatitis.html#dataset-geo-gse215457"]},{"id":"dataset:geo:gse215834","accession":"geo:GSE215834","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE215834","title":"Altered lipid homeostasis underlies selective neurodegeneration in SNX14 deficiency.","alternate_titles":[],"description":"Mouse cerebral-cortex and cerebellar bulk RNA sequencing in the viable constitutive Snx14 exon-14 frameshift study, spanning predegenerative and late ages. GEO SuperSeries combines the one-month and one-year experiments. This is model-organism tissue, not SCAR20 patient material.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:38625743"],"publication_contexts":[{"context_id":"disorder:Autosomal_Recessive_Spinocerebellar_Ataxia_20","publication":"PMID:38625743"}],"publication":"PMID:38625743","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38625743","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:38625743","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38625743","reference_title":"Altered lipid homeostasis is associated with cerebellar neurodegeneration in SNX14 deficiency.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"RNA-Seq data were deposited in GEO under the accession no. GSE215834.","explanation":"The primary study identifies the public transcriptomic dataset."}],"notes":["The same paper provides lipidomics in Supplemental Data 3; those measurements should not be described as RNA-seq data."],"contexts":[{"id":"disorder:Autosomal_Recessive_Spinocerebellar_Ataxia_20","name":"Autosomal Recessive Spinocerebellar Ataxia 20","kind":"Disorder","source_path":"kb/disorders/Autosomal_Recessive_Spinocerebellar_Ataxia_20.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autosomal_Recessive_Spinocerebellar_Ataxia_20.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Recessive_Spinocerebellar_Ataxia_20.html#dataset-geo-gse215834"}],"context_names":["Autosomal Recessive Spinocerebellar Ataxia 20"],"disease_names":["Autosomal Recessive Spinocerebellar Ataxia 20"],"disease_name":"Autosomal Recessive Spinocerebellar Ataxia 20","same_context_model_ids":["model:kb/disorders/Autosomal_Recessive_Spinocerebellar_Ataxia_20.yaml:Acute Snx14 knockdown in mouse cortical pyramidal neurons","model:kb/disorders/Autosomal_Recessive_Spinocerebellar_Ataxia_20.yaml:Conditional Snx14 mouse primary neuronal cultures","model:kb/disorders/Autosomal_Recessive_Spinocerebellar_Ataxia_20.yaml:Oleate-stimulated Snx14 exon-14 knockout cerebellar cultures","model:kb/disorders/Autosomal_Recessive_Spinocerebellar_Ataxia_20.yaml:Patient RNA assays for SNX14 splice variants","model:kb/disorders/Autosomal_Recessive_Spinocerebellar_Ataxia_20.yaml:Patient-derived neural progenitors","model:kb/disorders/Autosomal_Recessive_Spinocerebellar_Ataxia_20.yaml:SCAR20 patient dermal fibroblasts","model:kb/disorders/Autosomal_Recessive_Spinocerebellar_Ataxia_20.yaml:SNX14-depleted HEK293T spastin-turnover assays","model:kb/disorders/Autosomal_Recessive_Spinocerebellar_Ataxia_20.yaml:SNX14-knockout U2OS lipid and SCD1 rescue system"],"candidate_model_ids":["model:kb/disorders/Autosomal_Recessive_Spinocerebellar_Ataxia_20.yaml:Oleate-stimulated Snx14 exon-14 knockout cerebellar cultures"],"association_basis":"Same publication as a NAM (candidate)","nam_disease_context":"Same publication as a NAM (candidate)","source_paths":["kb/disorders/Autosomal_Recessive_Spinocerebellar_Ataxia_20.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autosomal_Recessive_Spinocerebellar_Ataxia_20.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Recessive_Spinocerebellar_Ataxia_20.html#dataset-geo-gse215834"]},{"id":"dataset:geo:gse21592","accession":"geo:GSE21592","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE21592","title":"Genome-wide gene expression profiling of human narcolepsy","alternate_titles":[],"description":"Study objectives: The objectives of this study was perform the global gene expression profiling aimed at identifying differentially expressed genes in the circulating lympho-monocytes of NRLCP patients affected by Narcolepsy with Cataplexy (NRLCP). Based on the tight association to the HLA-DQB1*0602 haplotype in caucasians, it could be hypotesized an immunological dysregulation underlying the pathogenesis of the disease. Design: 10 NRLCP patients with 10 healthy controls were compared. Total RNA isolated from blood specimens was analyzed using microarray technology followed by statistical data analysis to detect genome-wide differential gene expression between patients and controls.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[20],"sample_count":20,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:22783726"],"publication_contexts":[{"context_id":"disorder:Narcolepsy","publication":"PMID:22783726"}],"publication":"PMID:22783726","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/22783726","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Narcolepsy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Narcolepsy","name":"Narcolepsy","kind":"Disorder","source_path":"kb/disorders/Narcolepsy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Narcolepsy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Narcolepsy.html#dataset-geo-gse21592"}],"context_names":["Narcolepsy"],"disease_names":["Narcolepsy"],"disease_name":"Narcolepsy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Narcolepsy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Narcolepsy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Narcolepsy.html#dataset-geo-gse21592"]},{"id":"dataset:geo:gse216064","accession":"geo:GSE216064","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE216064","title":"scRNA-seq for analyzing the characteristics of PBMC in patients with autoimmune hepatitis","alternate_titles":[],"description":"Human peripheral-blood single-cell RNA-sequencing dataset comparing pooled PBMCs from four AIH patients with pooled PBMCs from four healthy controls.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"Homo sapiens","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"CL:0000842","label":"mononuclear leukocyte","display_label":"peripheral blood mononuclear cell","url":"http://purl.obolibrary.org/obo/CL_0000842"}],"sample_type_labels":["mononuclear leukocyte"],"sample_counts":[2],"sample_count":2,"conditions":["pooled PBMCs from four autoimmune hepatitis patients","pooled PBMCs from four healthy controls"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["10x Genomics Chromium 3' gene expression v2"],"platform":"10x Genomics Chromium 3' gene expression v2","publications":["PMID:38340154"],"publication_contexts":[{"context_id":"disorder:Autoimmune_Hepatitis","publication":"PMID:38340154"}],"publication":"PMID:38340154","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38340154","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE216064","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE216064","reference_title":"scRNA-seq for analyzing the characteristics of PBMC in patients with autoimmune hepatitis","supports":"SUPPORT","evidence_source":"OTHER","snippet":"This present study was designed to analyze the characteristics of AIH peripheral blood mononuclear cells (PBMCs) through single-cell RNA sequencing (scRNA-seq, 10x Genomics Gene Expression 3' Chromium V 2.0) and to explore the potential molecular mechanism of AIH.","explanation":"GEO metadata directly supports the disease, sample type, and assay."},{"reference":"PMID:38340154","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38340154","reference_title":"Characteristics of peripheral blood mononuclear cells and potential related molecular mechanisms in patients with autoimmune hepatitis: a single-cell RNA sequencing analysis.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"We generated 3690 and 3511 single-cell transcriptomes of PBMCs pooled from 4 healthy controls (HCs) and 4 AIH patients, respectively, by scRNA-seq.","explanation":"The publication defines the donor pools and cell-transcriptome counts."}],"notes":["GEO contains two pooled assay libraries, not eight independent libraries. The eight biological donors were pooled into one AIH and one control library, preventing donor-level estimation and leaving liver-tissue causality unresolved. The publication reports 3,511 AIH and 3,690 control cell transcriptomes."],"contexts":[{"id":"disorder:Autoimmune_Hepatitis","name":"Autoimmune Hepatitis","kind":"Disorder","source_path":"kb/disorders/Autoimmune_Hepatitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autoimmune_Hepatitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autoimmune_Hepatitis.html#dataset-geo-gse216064"}],"context_names":["Autoimmune Hepatitis"],"disease_names":["Autoimmune Hepatitis"],"disease_name":"Autoimmune Hepatitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Autoimmune_Hepatitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autoimmune_Hepatitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Autoimmune_Hepatitis.html#dataset-geo-gse216064"]},{"id":"dataset:geo:gse216841","accession":"geo:GSE216841","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE216841","title":"Idiopathic membranous nephropathy and minimal change disease (MCD) transcriptome","alternate_titles":[],"description":"Introduction: Minimal change disease (MCD) is a major cause of nephrotic syndrome. With a substantial number of patients requiring long-term immunosuppression leading to significant morbidity, the study aim was to determine MCD glomerular transcriptome to serve as a basis for biomarker discovery and novel drug target identification. Animal work showed podocyte injury induced by IL-7/IL-7R signaling (Zhai S, BBRC, 2018). Methods: Renal biopsies from adult patients representing the following groups were selected from the Norwegian Kidney Biopsy Registry: MCD (n=14), as well as normal tissue (n=8) and primary membranous nephropathy (MN; n=12) as the two reference groups.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[34],"sample_count":34,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:36672735"],"publication_contexts":[{"context_id":"disorder:Membranous_Nephropathy","publication":"PMID:36672735"},{"context_id":"disorder:Minimal_Change_Disease","publication":"PMID:36672735"}],"publication":"PMID:36672735","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36672735","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Membranous nephropathy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values.","Identified by GEO DataSets index search for Minimal Change Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Membranous_Nephropathy","name":"Membranous nephropathy","kind":"Disorder","source_path":"kb/disorders/Membranous_Nephropathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Membranous_Nephropathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Membranous_nephropathy.html#dataset-geo-gse216841"},{"id":"disorder:Minimal_Change_Disease","name":"Minimal Change Disease","kind":"Disorder","source_path":"kb/disorders/Minimal_Change_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Minimal_Change_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Minimal_Change_Disease.html#dataset-geo-gse216841"}],"context_names":["Membranous nephropathy","Minimal Change Disease"],"disease_names":["Membranous nephropathy","Minimal Change Disease"],"disease_name":"Membranous nephropathy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Membranous_Nephropathy.yaml","kb/disorders/Minimal_Change_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Membranous_Nephropathy.yaml","https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Minimal_Change_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Membranous_nephropathy.html#dataset-geo-gse216841","https://dismech.monarchinitiative.org/pages/disorders/Minimal_Change_Disease.html#dataset-geo-gse216841"]},{"id":"dataset:geo:gse216985","accession":"geo:GSE216985","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE216985","title":"A unique Mitochondrial Quality Control (MQC) mechanism reverses the phagosome maturation arrest caused by Mycobacterium tuberculosis","alternate_titles":[],"description":"Phagosome maturation arrest (PMA) imposed by Mycobacterium tuberculosis (Mtb) is among the classic tools that helps Mtb evade macrophage anti-bacterial response. Here we report a unique crosstalk between mitochondrial quality control (MQC) pathways and the phagosome maturation pathway, which unblocks the PMA and results in the efficient killing of Mtb. Depletion of p62/SQSTM1, a major autophagy adaptor, in human macrophages enhances Mtb killing. However, depletion of p62/SQSTM1 does not impact mitochondrial quality, despite an apparent block in mitophagy flux. Interestingly, in p62KD cells, MQC is ensured via TOM20+-mitochondria-derived vesicles (MDVs).","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[36],"sample_count":36,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Tuberculosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Tuberculosis","name":"Tuberculosis","kind":"Disorder","source_path":"kb/disorders/Tuberculosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Tuberculosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Tuberculosis.html#dataset-geo-gse216985"}],"context_names":["Tuberculosis"],"disease_names":["Tuberculosis"],"disease_name":"Tuberculosis","same_context_model_ids":["model:kb/disorders/Tuberculosis.yaml:Autologous iPSC-derived alveolus-on-chip (iLoC) Mtb infection model"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Tuberculosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Tuberculosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Tuberculosis.html#dataset-geo-gse216985"]},{"id":"dataset:geo:gse217001","accession":"geo:GSE217001","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE217001","title":"Variable phenotypes and penetrance between and within different zebrafish transition zone mutants","alternate_titles":[],"description":"Transcriptomic profiling of zebrafish transition zone mutants used to model ciliopathy phenotypes relevant to Joubert syndrome.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:7955","label":"Danio rerio","display_label":"zebrafish","url":"http://purl.obolibrary.org/obo/NCBITaxon_7955"}],"organism_labels":["Danio rerio"],"organism_label":"Danio rerio","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":["Joubert syndrome","zebrafish transition zone mutants"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["GEO"],"platform":"GEO","publications":["PMID:36533556"],"publication_contexts":[{"context_id":"disorder:Joubert_syndrome","publication":"PMID:36533556"}],"publication":"PMID:36533556","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36533556","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE217001","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE217001","reference_title":"Variable phenotypes and penetrance between and within different zebrafish transition zone mutants","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"Meckel Syndrome, Nephronophthisis, Joubert Syndrome, and Bardet-Biedl Syndrome have mutations in proteins that localize to the ciliary transition zone (TZ).","explanation":"This GEO series centers on transition zone mutants relevant to Joubert syndrome and other ciliopathies."}],"notes":[],"contexts":[{"id":"disorder:Joubert_syndrome","name":"Joubert syndrome","kind":"Disorder","source_path":"kb/disorders/Joubert_syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Joubert_syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Joubert_syndrome.html#dataset-geo-gse217001"}],"context_names":["Joubert syndrome"],"disease_names":["Joubert syndrome"],"disease_name":"Joubert syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Joubert_syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Joubert_syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Joubert_syndrome.html#dataset-geo-gse217001"]},{"id":"dataset:geo:gse217426","accession":"geo:GSE217426","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE217426","title":"Expression signature characteristic of Anaplastic Large Cell Lymphoma (ALCL) patients","alternate_titles":[],"description":"RNA extracted from tumor biopsies of 44 patients affected by ALCL was analyzed on the nCounter system using a custom panel called VF_150921 (Nanostring Technologies).","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[44],"sample_count":44,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37381763"],"publication_contexts":[{"context_id":"disorder:Anaplastic_Large_Cell_Lymphoma","publication":"PMID:37381763"}],"publication":"PMID:37381763","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37381763","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Anaplastic Large Cell Lymphoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Anaplastic_Large_Cell_Lymphoma","name":"Anaplastic Large Cell Lymphoma","kind":"Disorder","source_path":"kb/disorders/Anaplastic_Large_Cell_Lymphoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Anaplastic_Large_Cell_Lymphoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Anaplastic_Large_Cell_Lymphoma.html#dataset-geo-gse217426"}],"context_names":["Anaplastic Large Cell Lymphoma"],"disease_names":["Anaplastic Large Cell Lymphoma"],"disease_name":"Anaplastic Large Cell Lymphoma","same_context_model_ids":["model:kb/disorders/Anaplastic_Large_Cell_Lymphoma.yaml:Dominant-Negative STAT3 in Karpas 299 and SU-DHL-1 Cells"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Anaplastic_Large_Cell_Lymphoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Anaplastic_Large_Cell_Lymphoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Anaplastic_Large_Cell_Lymphoma.html#dataset-geo-gse217426"]},{"id":"dataset:geo:gse217516","accession":"geo:GSE217516","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE217516","title":"Single-cell RNA-sequencing of bronchoalveolar lavage cells from humans with bronchiectasis","alternate_titles":[],"description":"Bronchiectasis is a lung disease characterized by irreversible dilation of the large airways (bronchodilatation), which often causes recurrent airway infection and non-resolving inflammation. In this study, we performed single-cell RNA-sequencing (scRNA-seq) to determine the heterogeneity of immune cells in the airways of bronchiectasis patients.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41774079"],"publication_contexts":[{"context_id":"disorder:Bronchiectasis","publication":"PMID:41774079"}],"publication":"PMID:41774079","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41774079","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Bronchiectasis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Bronchiectasis","name":"Bronchiectasis","kind":"Disorder","source_path":"kb/disorders/Bronchiectasis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bronchiectasis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Bronchiectasis.html#dataset-geo-gse217516"}],"context_names":["Bronchiectasis"],"disease_names":["Bronchiectasis"],"disease_name":"Bronchiectasis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Bronchiectasis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bronchiectasis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Bronchiectasis.html#dataset-geo-gse217516"]},{"id":"dataset:geo:gse217667","accession":"geo:GSE217667","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE217667","title":"Molecular correlates of vaccine-induced protection against typhoid fever","alternate_titles":[],"description":"Blood bulk RNA-seq from adult human volunteers in a controlled human infection model after ViPS or ViTCV vaccination and S. Typhi challenge.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[521],"sample_count":521,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37402153"],"publication_contexts":[{"context_id":"disorder:Typhoid_Fever","publication":"PMID:37402153"}],"publication":"PMID:37402153","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37402153","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Typhoid Fever; accession and metadata verified against NCBI E-utilities on 2026-09-25. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Typhoid_Fever","name":"Typhoid Fever","kind":"Disorder","source_path":"kb/disorders/Typhoid_Fever.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Typhoid_Fever.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Typhoid_Fever.html#dataset-geo-gse217667"}],"context_names":["Typhoid Fever"],"disease_names":["Typhoid Fever"],"disease_name":"Typhoid Fever","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Typhoid_Fever.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Typhoid_Fever.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Typhoid_Fever.html#dataset-geo-gse217667"]},{"id":"dataset:geo:gse218012","accession":"geo:GSE218012","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE218012","title":"Whole-transcriptome analysis of dermal fibroblasts from patients with hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorders supports their categorization as a single clinical entity with a contribution of inflammatory pathways","alternate_titles":[],"description":"Hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD) are clinically overlapping connective tissue disorders of unknown etiology and without any validated diagnostic biomarker and specific therapies. Herein, we in-depth characterized the cellular phenotype and gene expression profile of hEDS and HSD dermal fibroblasts by immunofluorescence, amplicon-based RNA-seq, and qPCR. We demonstrated that both cell types show a common cellular trait, i.e., generalized extracellular matrix (ECM) disarray, myofibroblast differentiation, and dysregulated gene expression.","alternate_descriptions":["Amplicon-based RNA-seq of cultured dermal fibroblasts from 20 hEDS patients, 20 HSD patients, and 40 healthy donors. The largest public hEDS omics resource, and the only one powered to test whether a transcriptional boundary separates hEDS from HSD. Note that sample_count (200) is the GEO GSM sample count and is distinct from the 80 donors; the GEO series lists biological and technical replicates per donor as separate samples."],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"CL:0002620","label":"skin fibroblast","display_label":"skin fibroblast","url":"http://purl.obolibrary.org/obo/CL_0002620"}],"sample_type_labels":["skin fibroblast"],"sample_counts":[200],"sample_count":200,"conditions":["Hypermobile Ehlers-Danlos syndrome","Hypermobility spectrum disorder","Healthy donor control"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["GPL23934 Ion Torrent S5 (Homo sapiens)"],"platform":"GPL23934 Ion Torrent S5 (Homo sapiens)","publications":["PMID:36552803"],"publication_contexts":[{"context_id":"disorder:Ehlers-Danlos_Syndrome","publication":"PMID:36552803"},{"context_id":"disorder:Hypermobile_Ehlers-Danlos_Syndrome","publication":"PMID:36552803"}],"publication":"PMID:36552803","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36552803","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:36552803","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/36552803","reference_title":"RNA-Seq of Dermal Fibroblasts from Patients with Hypermobile Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorders Supports Their Categorization as a Single Entity with Involvement of Extracellular Matrix Degrading and Proinflammatory Pathomechanisms.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We demonstrated that both cell types show a common cellular trait, i.e., generalized extracellular matrix (ECM) disarray, myofibroblast differentiation, and dysregulated gene expression.","explanation":"The associated publication reports that hEDS and HSD fibroblasts share the ECM-disarray and myofibroblast phenotype, which is the claim this dataset is cited to support."}],"notes":["Identified by GEO DataSets index search for Ehlers-Danlos Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Ehlers-Danlos_Syndrome","name":"Ehlers-Danlos Syndrome","kind":"Disorder","source_path":"kb/disorders/Ehlers-Danlos_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ehlers-Danlos_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Ehlers-Danlos_Syndrome.html#dataset-geo-gse218012"},{"id":"disorder:Hypermobile_Ehlers-Danlos_Syndrome","name":"Hypermobile Ehlers-Danlos Syndrome","kind":"Disorder","source_path":"kb/disorders/Hypermobile_Ehlers-Danlos_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hypermobile_Ehlers-Danlos_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hypermobile_Ehlers-Danlos_Syndrome.html#dataset-geo-gse218012"}],"context_names":["Ehlers-Danlos Syndrome","Hypermobile Ehlers-Danlos Syndrome"],"disease_names":["Ehlers-Danlos Syndrome","Hypermobile Ehlers-Danlos Syndrome"],"disease_name":"Ehlers-Danlos Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Ehlers-Danlos_Syndrome.yaml","kb/disorders/Hypermobile_Ehlers-Danlos_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ehlers-Danlos_Syndrome.yaml","https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hypermobile_Ehlers-Danlos_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Ehlers-Danlos_Syndrome.html#dataset-geo-gse218012","https://dismech.monarchinitiative.org/pages/disorders/Hypermobile_Ehlers-Danlos_Syndrome.html#dataset-geo-gse218012"]},{"id":"dataset:geo:gse218549","accession":"geo:GSE218549","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE218549","title":"DNA-Methylation Analysis as a Tool for Thymoma Classification","alternate_titles":[],"description":"Thymomas are malignant thymic epithelial tumors that are difficult to diagnose due to their rarity and complex diagnostic criteria. They represent a morphologically heterogeneous class of tumors mainly defined by “organo-typical” architectural features and cellular composition. The diagnosis of thymoma is burdened with a high inter-observer variability and with the problem that some type-specific morphological alterations are rather a continuum than clear-cut. Methylation pattern-based classification may help to increase diagnostic precision, particularly in borderline cases.","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[122],"sample_count":122,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:36497358"],"publication_contexts":[{"context_id":"disorder:Thymoma","publication":"PMID:36497358"}],"publication":"PMID:36497358","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36497358","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Thymoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Thymoma","name":"Thymoma","kind":"Disorder","source_path":"kb/disorders/Thymoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Thymoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Thymoma.html#dataset-geo-gse218549"}],"context_names":["Thymoma"],"disease_names":["Thymoma"],"disease_name":"Thymoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Thymoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Thymoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Thymoma.html#dataset-geo-gse218549"]},{"id":"dataset:geo:gse218974","accession":"geo:GSE218974","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE218974","title":"Single-cell profiling of alveolar rhabdomyosarcoma reveals RAS pathway inhibitors as cell-fate hijackers with therapeutic relevance","alternate_titles":[],"description":"scRNA-seq of patient-derived aRMS and eRMS primary cultures plus RH4/RH30 cell lines (~53,000 cells total). Identifies a PAX3::FOXO1-stabilized \"myogenin+ cycling progenitor\" cell state that persists across individual tumors. PAX3::FOXO1 shRNA knockdown releases the differentiation block and shifts cells toward a myogenin-high differentiated state. Companion CyTOF mass cytometry and a 244-compound phenotypic drug screen (MYOscopy imaging) identify MEK inhibitor (trametinib) + RAF inhibitor (dabrafenib) as cell-fate hijackers that redirect aRMS toward differentiation. Survival analysis shows the progenitor/MuSC-like transcriptional signature correlates with inferior patient outcomes.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0001134","label":"skeletal muscle tissue","display_label":"skeletal muscle tissue","url":"http://purl.obolibrary.org/obo/UBERON_0001134"}],"sample_type_labels":["skeletal muscle tissue"],"sample_counts":[7],"sample_count":7,"conditions":["alveolar rhabdomyosarcoma (aRMS) patient-derived cultures","embryonal rhabdomyosarcoma (eRMS)","PAX3::FOXO1 shRNA knockdown"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["10x Genomics Chromium; Illumina NovaSeq 6000"],"platform":"10x Genomics Chromium; Illumina NovaSeq 6000","publications":["PMID:36753540"],"publication_contexts":[{"context_id":"disorder:Alveolar_Rhabdomyosarcoma","publication":"PMID:36753540"}],"publication":"PMID:36753540","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36753540","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:36753540","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/36753540","reference_title":"Single-cell profiling of alveolar rhabdomyosarcoma reveals RAS pathway inhibitors as cell-fate hijackers with therapeutic relevance.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Here, we combined single-cell RNA sequencing, mass cytometry, and high-content imaging to resolve intratumoral heterogeneity of patient-derived primary RMS cultures.","explanation":"Supports the patient-derived single-cell culture dataset and its multimodal profiling design."}],"notes":["GEO series GSE218974 (7 samples, ~53,000 cells). Companion CyTOF data and 244-compound drug screen (MYOscopy) data are not deposited to GEO but are described in PMID:36753540. Most ARMS-focused scRNA-seq dataset; directly interrogates the PAX3::FOXO1 cell-fate lock with perturbation experiments."],"contexts":[{"id":"disorder:Alveolar_Rhabdomyosarcoma","name":"Alveolar Rhabdomyosarcoma","kind":"Disorder","source_path":"kb/disorders/Alveolar_Rhabdomyosarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alveolar_Rhabdomyosarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Alveolar_Rhabdomyosarcoma.html#dataset-geo-gse218974"}],"context_names":["Alveolar Rhabdomyosarcoma"],"disease_names":["Alveolar Rhabdomyosarcoma"],"disease_name":"Alveolar Rhabdomyosarcoma","same_context_model_ids":["model:kb/disorders/Alveolar_Rhabdomyosarcoma.yaml:Fusion-positive RMS cancer-associated fibroblast coculture","model:kb/disorders/Alveolar_Rhabdomyosarcoma.yaml:Patient-derived ARMS single-cell culture model"],"candidate_model_ids":["model:kb/disorders/Alveolar_Rhabdomyosarcoma.yaml:Patient-derived ARMS single-cell culture model"],"association_basis":"Same publication as a NAM (candidate)","nam_disease_context":"Same publication as a NAM (candidate)","source_paths":["kb/disorders/Alveolar_Rhabdomyosarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alveolar_Rhabdomyosarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Alveolar_Rhabdomyosarcoma.html#dataset-geo-gse218974"]},{"id":"dataset:geo:gse219036","accession":"geo:GSE219036","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE219036","title":"Virological characterization of the 2022 outbreak-causing monkeypox virus using human keratinocytes and colon organoids","alternate_titles":[],"description":"RNA-seq comparing 2022 outbreak strain to endemic MPXV clades (I, IIa, IIb) in human keratinocytes and iPSC-derived colon organoids. Found MPXV replication more productive in keratinocytes and unique hypoxia-related gene expression triggered by 2022 outbreak strain.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"CL:0000312","label":"keratinocyte","display_label":"keratinocyte","url":"http://purl.obolibrary.org/obo/CL_0000312"}],"sample_type_labels":["keratinocyte"],"sample_counts":[24],"sample_count":24,"conditions":["mock infected","MPXV clade I infected","MPXV clade IIa infected","MPXV clade IIb (2022 outbreak) infected"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Key dataset for understanding 2022 outbreak strain virological properties and host cell damage mechanisms. Identifies distinct gene expression patterns between clades."],"contexts":[{"id":"disorder:Monkeypox","name":"Monkeypox","kind":"Disorder","source_path":"kb/disorders/Monkeypox.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Monkeypox.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Monkeypox.html#dataset-geo-gse219036"}],"context_names":["Monkeypox"],"disease_names":["Monkeypox"],"disease_name":"Monkeypox","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Monkeypox.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Monkeypox.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Monkeypox.html#dataset-geo-gse219036"]},{"id":"dataset:geo:gse220100","accession":"geo:GSE220100","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE220100","title":"Targeted transcriptional analysis of IgA vasculitis, IgA nephropathy, and IgA dominant infection related glomerulonephritis","alternate_titles":[],"description":"This study identifies immune transcript signatures that may predict IgAV nephritis in skin biopsies and distinguish IgA-IRGN from IgAN and IgAV in kidney biopsies","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[24],"sample_count":24,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37036681"],"publication_contexts":[{"context_id":"disorder:IgA_Vasculitis","publication":"PMID:37036681"}],"publication":"PMID:37036681","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37036681","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for IgA Vasculitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:IgA_Vasculitis","name":"IgA Vasculitis","kind":"Disorder","source_path":"kb/disorders/IgA_Vasculitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/IgA_Vasculitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/IgA_Vasculitis.html#dataset-geo-gse220100"}],"context_names":["IgA Vasculitis"],"disease_names":["IgA Vasculitis"],"disease_name":"IgA Vasculitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/IgA_Vasculitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/IgA_Vasculitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/IgA_Vasculitis.html#dataset-geo-gse220100"]},{"id":"dataset:geo:gse220268","accession":"geo:GSE220268","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE220268","title":"Identification of a transcriptomic signature of X chromosome overdosage in  Saudi Klinefelter syndrome iPSCs.","alternate_titles":[],"description":"Klinefelter syndrome (KS) is the most prevalent aneuploidy in males and is characterized by an extra copy of the X chromosome,while the non-mosaic form of KS with 47,XXY karyotype is the most frequent (80-90%), less common non-disjunction events during the early mitotic division of the zygote result in mosaic forms of KS (47,XXY/46,XY). Here, using a paradigmatic cohort of KS-inducible pluripotent stem cells (iPSCs) carrying 47,XXY karyotypes we present the first iPSC-based disease-modeling study performed on KS patients from Saudi Arabia. We profiled the transcriptome of these Saudi KS-iPSCs, virtually characterized by subduedcgenetic backgrounds.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[45],"sample_count":45,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:36971776"],"publication_contexts":[{"context_id":"disorder:Klinefelter_Syndrome","publication":"PMID:36971776"}],"publication":"PMID:36971776","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36971776","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Klinefelter Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Klinefelter_Syndrome","name":"Klinefelter Syndrome","kind":"Disorder","source_path":"kb/disorders/Klinefelter_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Klinefelter_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Klinefelter_Syndrome.html#dataset-geo-gse220268"}],"context_names":["Klinefelter Syndrome"],"disease_names":["Klinefelter Syndrome"],"disease_name":"Klinefelter Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Klinefelter_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Klinefelter_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Klinefelter_Syndrome.html#dataset-geo-gse220268"]},{"id":"dataset:geo:gse220308","accession":"geo:GSE220308","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE220308","title":"Stratification of expression profiles of immune-related genes in the lesion of cutaneous leishmaniasis patients with L. major and L. tropica infection","alternate_titles":[],"description":"There is still no reliable human vaccination against cutaneous leishmaniasis (CL), a serious public health issue in many parts of underdeveloped nations like Morocco and Iran. There are few studies comparing the expression of immune-related genes in the skin lesions of CL patients infected with L. major and L. tropica. In this study, we used dcRT-MLPA to analyze the expression profiles of 144 immune response-related genes in CL patients from Morocco and Iran who had been exposed to L. major and L. tropica, respectively.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[40],"sample_count":40,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40100809"],"publication_contexts":[{"context_id":"disorder:Leishmaniasis","publication":"PMID:40100809"}],"publication":"PMID:40100809","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40100809","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Leishmaniasis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Leishmaniasis","name":"Leishmaniasis","kind":"Disorder","source_path":"kb/disorders/Leishmaniasis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Leishmaniasis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Leishmaniasis.html#dataset-geo-gse220308"}],"context_names":["Leishmaniasis"],"disease_names":["Leishmaniasis"],"disease_name":"Leishmaniasis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Leishmaniasis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Leishmaniasis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Leishmaniasis.html#dataset-geo-gse220308"]},{"id":"dataset:geo:gse220582","accession":"geo:GSE220582","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE220582","title":"Transcriptomic analysis of double-negative B cell subsets in IgG4-related disease","alternate_titles":[],"description":"IgD-CD27- “double negative” (DN) B cells are known to be expanded in the blood in many disease contexts and the IgD-CD27-CXCR5-CD11c+ DN2 B cell subset has been most widely studied in autoimmune diseases. In addition to DN2 B cells, a distinct IgD-CD27-CXCR5-CD11c- DN3 B cell subset accumulates in the blood both in IgG4-related disease, an autoimmune disease in which inflammation and fibrosis can be reversed by B cell depletion, and in severe COVID-19. DN3 B cells, but not DN2 B cells, prominently accumulate in the blood and end-organs of IgG4-related disease.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[15],"sample_count":15,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37300833"],"publication_contexts":[{"context_id":"disorder:IgG4-Related_Disease","publication":"PMID:37300833"}],"publication":"PMID:37300833","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37300833","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for IgG4-Related Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:IgG4-Related_Disease","name":"IgG4-Related Disease","kind":"Disorder","source_path":"kb/disorders/IgG4-Related_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/IgG4-Related_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/IgG4-Related_Disease.html#dataset-geo-gse220582"}],"context_names":["IgG4-Related Disease"],"disease_names":["IgG4-Related Disease"],"disease_name":"IgG4-Related Disease","same_context_model_ids":["model:kb/disorders/IgG4-Related_Disease.yaml:Anti-IL-1RA functional cell assays","model:kb/disorders/IgG4-Related_Disease.yaml:Human cholangiocyte protective-barrier assays","model:kb/disorders/IgG4-Related_Disease.yaml:Patient B-cell and fibroblast coculture","model:kb/disorders/IgG4-Related_Disease.yaml:Patient Tfh and B-cell coculture"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/IgG4-Related_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/IgG4-Related_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/IgG4-Related_Disease.html#dataset-geo-gse220582"]},{"id":"dataset:geo:gse220725","accession":"geo:GSE220725","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE220725","title":"Oxidative phosphorylation is a pivotal therapeutic target of fibrodysplasia ossificans progressiva","alternate_titles":[],"description":"Heterotopic ossification (HO) is a non-physiological process of bone formation in which progenitor cells in soft tissues differentiate into chondrogenic cells. In the case of fibrodysplasia ossificans progressiva (FOP), a rare genetic disease characterized by progressive and systemic HO, the Activin A/mutated-ACVR1/mTORC1 cascade induces HO in progenitors, one of which is the fibro/adipogenic progenitors (FAPs) in muscle tissues. The relevant biological processes aberrantly regulated by activated mTORC1 remain unclear, however.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[21],"sample_count":21,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:38365425"],"publication_contexts":[{"context_id":"disorder:Fibrodysplasia_Ossificans_Progressiva","publication":"PMID:38365425"}],"publication":"PMID:38365425","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38365425","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Fibrodysplasia Ossificans Progressiva (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Fibrodysplasia_Ossificans_Progressiva","name":"Fibrodysplasia Ossificans Progressiva","kind":"Disorder","source_path":"kb/disorders/Fibrodysplasia_Ossificans_Progressiva.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fibrodysplasia_Ossificans_Progressiva.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Fibrodysplasia_Ossificans_Progressiva.html#dataset-geo-gse220725"}],"context_names":["Fibrodysplasia Ossificans Progressiva"],"disease_names":["Fibrodysplasia Ossificans Progressiva"],"disease_name":"Fibrodysplasia Ossificans Progressiva","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Fibrodysplasia_Ossificans_Progressiva.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fibrodysplasia_Ossificans_Progressiva.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Fibrodysplasia_Ossificans_Progressiva.html#dataset-geo-gse220725"]},{"id":"dataset:geo:gse221004","accession":"geo:GSE221004","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE221004","title":"Effect of smooth muscle specific PRDM6 depletion on Aorta and Ductus Arterious (DA) development","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[24],"sample_count":24,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:9350","label":"PRDM6","display_label":"PRDM6","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/9350"}],"genes":["PRDM6"],"platforms":[],"platform":null,"publications":["PMID:36749647"],"publication_contexts":[{"context_id":"disorder:Patent_Ductus_Arteriosus_3","publication":"PMID:36749647"}],"publication":"PMID:36749647","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36749647","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["The RNA-seq comparison of ductus arteriosus against ascending aorta with and without Prdm6 depletion that identifies the downregulated ductus-enriched contractile gene program curated in this entry. Relevance triaged manually: the series is about the ductus arteriosus and the causal gene of this entry, not merely a PRDM6 gene-name match."],"contexts":[{"id":"disorder:Patent_Ductus_Arteriosus_3","name":"Patent Ductus Arteriosus 3","kind":"Disorder","source_path":"kb/disorders/Patent_Ductus_Arteriosus_3.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Patent_Ductus_Arteriosus_3.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Patent_Ductus_Arteriosus_3.html#dataset-geo-gse221004"}],"context_names":["Patent Ductus Arteriosus 3"],"disease_names":["Patent Ductus Arteriosus 3"],"disease_name":"Patent Ductus Arteriosus 3","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Patent_Ductus_Arteriosus_3.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Patent_Ductus_Arteriosus_3.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Patent_Ductus_Arteriosus_3.html#dataset-geo-gse221004"]},{"id":"dataset:geo:gse221091","accession":"geo:GSE221091","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE221091","title":"RNA-Seq of CD19+ B-cell, CD14+ monocyte, CD4+ and CD8+ T cell populations from patients with juvenile dermatomyositis and controls","alternate_titles":[],"description":"RNA sequencing was used to compare the transcriptional state of ex-vivo B-cells, moncytes and T-cells from children with Juvenile dermatomyositis (JDM) pre- and on-treatment and age-matched healthy controls. RNA was extracted from blood samples that were taken from juvenile dermatomyositis patients at diagnosis (before they received treatment) and approximately a year into treatment. The treatment included oral prednisolone, methotrexate, azathioprine, cyclophosphamide and other drugs.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[106],"sample_count":106,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:36564154"],"publication_contexts":[{"context_id":"disorder:Dermatomyositis","publication":"PMID:36564154"}],"publication":"PMID:36564154","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36564154","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Dermatomyositis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Dermatomyositis","name":"Dermatomyositis","kind":"Disorder","source_path":"kb/disorders/Dermatomyositis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dermatomyositis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Dermatomyositis.html#dataset-geo-gse221091"}],"context_names":["Dermatomyositis"],"disease_names":["Dermatomyositis"],"disease_name":"Dermatomyositis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Dermatomyositis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dermatomyositis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Dermatomyositis.html#dataset-geo-gse221091"]},{"id":"dataset:geo:gse221094","accession":"geo:GSE221094","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE221094","title":"Determining the PRDM6 genomic binding sites in primary outflow tract smooth muscle cells","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["CHIP_SEQ"],"data_type_labels":["Chromatin immunoprecipitation sequencing"],"data_type_label":"Chromatin immunoprecipitation sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[4],"sample_count":4,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:9350","label":"PRDM6","display_label":"PRDM6","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/9350"}],"genes":["PRDM6"],"platforms":[],"platform":null,"publications":["PMID:36749647"],"publication_contexts":[{"context_id":"disorder:Patent_Ductus_Arteriosus_3","publication":"PMID:36749647"}],"publication":"PMID:36749647","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36749647","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["The ChIP-seq series behind the finding that half the genes altered by Prdm6 depletion carry Prdm6 binding sites, which is what supports a primary transcriptional mechanism in this entry rather than a secondary effect."],"contexts":[{"id":"disorder:Patent_Ductus_Arteriosus_3","name":"Patent Ductus Arteriosus 3","kind":"Disorder","source_path":"kb/disorders/Patent_Ductus_Arteriosus_3.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Patent_Ductus_Arteriosus_3.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Patent_Ductus_Arteriosus_3.html#dataset-geo-gse221094"}],"context_names":["Patent Ductus Arteriosus 3"],"disease_names":["Patent Ductus Arteriosus 3"],"disease_name":"Patent Ductus Arteriosus 3","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Patent_Ductus_Arteriosus_3.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Patent_Ductus_Arteriosus_3.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Patent_Ductus_Arteriosus_3.html#dataset-geo-gse221094"]},{"id":"dataset:geo:gse221921","accession":"geo:GSE221921","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE221921","title":"Identification of unique genomic signatures in patients with fibromyalgia and chronic pain","alternate_titles":[],"description":"Fibromyalgia is a chronic pain syndrome characterized by widespread pain. The pathophysiology of fibromyalgia is not clearly understood and there are no specific biomarkers available for accurate diagnosis. Here we define genomic signatures using high throughput RNA sequencing on 96 fibromyalgia and 93 matched controls. Our findings revealed two major fibromyalgia-associated expression signatures. The first group included 44 patients with a signature enriched for gene expression associated with extracellular matrix and downregulation of RhoGDI signaling pathway.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[189],"sample_count":189,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:38366049"],"publication_contexts":[{"context_id":"disorder:Fibromyalgia","publication":"PMID:38366049"}],"publication":"PMID:38366049","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38366049","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Fibromyalgia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Fibromyalgia","name":"Fibromyalgia","kind":"Disorder","source_path":"kb/disorders/Fibromyalgia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fibromyalgia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Fibromyalgia.html#dataset-geo-gse221921"}],"context_names":["Fibromyalgia"],"disease_names":["Fibromyalgia"],"disease_name":"Fibromyalgia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Fibromyalgia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fibromyalgia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Fibromyalgia.html#dataset-geo-gse221921"]},{"id":"dataset:geo:gse222215","accession":"geo:GSE222215","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE222215","title":"Expression of neutrophilic genes in patients diagnosed with Kawasaki disease and healthy controls","alternate_titles":[],"description":"Kawasaki disease (KD) is considered the main contributor to acquired heart diseases in developed countries. However, the precise pathogenesis of KD remains unclear. Neutrophils played roles in KD. This study aimed to select hub genes in neutrophils in acute KD. mRNA microarray of neutrophils from four acute KD patients and three healthy controls was performed to screen differentially expressed mRNAs (DE-mRNAs). DE-mRNAs were analyzed and predicted by Gene Ontology (GO), Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways, and protein-protein interaction networks.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[7],"sample_count":7,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37394620"],"publication_contexts":[{"context_id":"disorder:Kawasaki_Disease","publication":"PMID:37394620"}],"publication":"PMID:37394620","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37394620","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Kawasaki Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. 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adult mice and collected inguinal lymph nodes for transcriptome analyses.","explanation":"This supports transcriptomic profiling of lymphoid tissue to characterize systemic inflammatory mechanisms in NS models."}],"notes":[],"contexts":[{"id":"disorder:Netherton_Syndrome","name":"Netherton syndrome","kind":"Disorder","source_path":"kb/disorders/Netherton_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Netherton_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Netherton_syndrome.html#dataset-geo-gse224409"}],"context_names":["Netherton syndrome"],"disease_names":["Netherton syndrome"],"disease_name":"Netherton syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association 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Relevance confirmed manually; retrieved 2026-08-15."],"contexts":[{"id":"disorder:Chromophobe_Renal_Cell_Carcinoma","name":"Chromophobe Renal Cell Carcinoma","kind":"Disorder","source_path":"kb/disorders/Chromophobe_Renal_Cell_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chromophobe_Renal_Cell_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chromophobe_Renal_Cell_Carcinoma.html#dataset-geo-gse224415"}],"context_names":["Chromophobe Renal Cell Carcinoma"],"disease_names":["Chromophobe Renal Cell Carcinoma"],"disease_name":"Chromophobe Renal Cell Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chromophobe_Renal_Cell_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chromophobe_Renal_Cell_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chromophobe_Renal_Cell_Carcinoma.html#dataset-geo-gse224415"]},{"id":"dataset:geo:gse224860","accession":"geo:GSE224860","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE224860","title":"Bulk RNA-seq of brain samples from fetuses with Tay-Sachs Disease","alternate_titles":[],"description":"Bulk RNA-seq from regional fetal brain tissue with biallelic pathogenic HEXA variants and controls. 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Publication: PMID:36700853. No raw-data reanalysis was performed for this review; multiple tissue regions must not be treated as independent donors."],"contexts":[{"id":"disorder:Tay-Sachs_Disease","name":"Tay-Sachs Disease","kind":"Disorder","source_path":"kb/disorders/Tay-Sachs_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Tay-Sachs_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Tay-Sachs_Disease.html#dataset-geo-gse224860"}],"context_names":["Tay-Sachs Disease"],"disease_names":["Tay-Sachs Disease"],"disease_name":"Tay-Sachs Disease","same_context_model_ids":["model:kb/disorders/Tay-Sachs_Disease.yaml:GM2-loaded neuronal cultures","model:kb/disorders/Tay-Sachs_Disease.yaml:Patient-derived GM2 skin fibroblasts","model:kb/disorders/Tay-Sachs_Disease.yaml:Sandhoff cerebral organoids with isogenic correction"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Tay-Sachs_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Tay-Sachs_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Tay-Sachs_Disease.html#dataset-geo-gse224860"]},{"id":"dataset:geo:gse225031","accession":"geo:GSE225031","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE225031","title":"Mutation of PAX3 gene impairs otic vesicles via inhibiting the Wnt1/β-catenin signaling pathway in inner ear organoids of Waardenburg syndrome type I","alternate_titles":[],"description":"To investigate pathogenic mechnism of hearing loss in inner ear organoids in PAX3 gene mutation of WS1 patient in vitro , we established the iPSCs line from one WS1 patient carrying a heterozygous mutation in the PAX3 gene and one healthy control. 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These iPSCs were differentiated into inner ear organoid-like structure with otic vesicles-specific marker.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for PAX3-Related Waardenburg Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:PAX3_Waardenburg_Spectrum","name":"PAX3-Related Waardenburg Syndrome","kind":"Disorder","source_path":"kb/disorders/PAX3_Waardenburg_Spectrum.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/PAX3_Waardenburg_Spectrum.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/PAX3-Related_Waardenburg_Syndrome.html#dataset-geo-gse225031"}],"context_names":["PAX3-Related Waardenburg Syndrome"],"disease_names":["PAX3-Related Waardenburg Syndrome"],"disease_name":"PAX3-Related Waardenburg Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/PAX3_Waardenburg_Spectrum.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/PAX3_Waardenburg_Spectrum.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/PAX3-Related_Waardenburg_Syndrome.html#dataset-geo-gse225031"]},{"id":"dataset:geo:gse225178","accession":"geo:GSE225178","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE225178","title":"Association of immune related expression profile with sensitivity to neoadjuvant chemotherapy using docetaxel, cisplatin and 5-fluorouracil in esophageal squamous cell carcinoma.","alternate_titles":[],"description":"Neoadjuvant chemotherapy (NAC) followed by surgery is one of the standard therapeutic approaches for patients with locally advanced esophageal carcinoma in Japan. Recently, JCOG1109 study revealed that NAC with docetaxel, cisplatin and 5-fluorouracil (5-FU) (DCF-NAC) is superior to NAC with cisplatin and 5-FU, and has become the standard preoperative chemotherapy. By using microarray, we have previously investigated expression profiles of endoscopic biopsies of patients with esophageal squamous cell carcinoma (ESCC) before DCF-NAC (preNAC) and identified 17 molecules as predictive biomarkers for pathologically complete response to DCF-NAC.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[44],"sample_count":44,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37715346"],"publication_contexts":[{"context_id":"disorder:Esophageal_Carcinoma","publication":"PMID:37715346"}],"publication":"PMID:37715346","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37715346","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Esophageal Carcinoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Esophageal_Carcinoma","name":"Esophageal Carcinoma","kind":"Disorder","source_path":"kb/disorders/Esophageal_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Esophageal_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Esophageal_Carcinoma.html#dataset-geo-gse225178"}],"context_names":["Esophageal Carcinoma"],"disease_names":["Esophageal Carcinoma"],"disease_name":"Esophageal Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Esophageal_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Esophageal_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Esophageal_Carcinoma.html#dataset-geo-gse225178"]},{"id":"dataset:geo:gse22523","accession":"geo:GSE22523","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE22523","title":"Analysis of vitamin D response element binding protein target genes reveals a role for vitamin D in osteoblast mTOR signaling","alternate_titles":[],"description":"Human expression microarray comparing EBV-transformed B-cell lines from the single VDDR2B index patient and a matched control, each with vehicle or 1,25-dihydroxyvitamin D exposure in biological duplicate. The resource tests the index-case cellular transcriptional response; it is not a cohort of the Cauca cluster.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"CL:0000236","label":"B cell","display_label":"B cell","url":"http://purl.obolibrary.org/obo/CL_0000236"}],"sample_type_labels":["B cell"],"sample_counts":[8],"sample_count":8,"conditions":["Index-patient EBV B cells with vehicle","Index-patient EBV B cells with 1,25-dihydroxyvitamin D","Matched-control EBV B cells with vehicle","Matched-control EBV B cells with 1,25-dihydroxyvitamin D"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["GPL6244"],"platform":"GPL6244","publications":["PMID:21123297"],"publication_contexts":[{"context_id":"disorder:Vitamin_D-Dependent_Rickets_Type_2B","publication":"PMID:21123297"}],"publication":"PMID:21123297","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/21123297","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Official NCBI GEO metadata verified on 2026-08-20: eight human samples, platform GPL6244, two biological replicates per four condition groups, and PMID:21123297. GSE63086 is deliberately omitted because it is an MG63 mechanistic perturbation dataset rather than a patient VDDR2B resource."],"contexts":[{"id":"disorder:Vitamin_D-Dependent_Rickets_Type_2B","name":"Vitamin D-Dependent Rickets Type 2B","kind":"Disorder","source_path":"kb/disorders/Vitamin_D-Dependent_Rickets_Type_2B.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Vitamin_D-Dependent_Rickets_Type_2B.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Vitamin_D-Dependent_Rickets_Type_2B.html#dataset-geo-gse22523"}],"context_names":["Vitamin D-Dependent Rickets Type 2B"],"disease_names":["Vitamin D-Dependent Rickets Type 2B"],"disease_name":"Vitamin D-Dependent Rickets Type 2B","same_context_model_ids":["model:kb/disorders/Vitamin_D-Dependent_Rickets_Type_2B.yaml:Heterologous CV-1 transfer of index-case VDR cDNA","model:kb/disorders/Vitamin_D-Dependent_Rickets_Type_2B.yaml:HKC-8 HNRNPC C1/C2 overexpression system","model:kb/disorders/Vitamin_D-Dependent_Rickets_Type_2B.yaml:Index-case EBV-transformed B-cell line","model:kb/disorders/Vitamin_D-Dependent_Rickets_Type_2B.yaml:Index-case skin fibroblast culture","model:kb/disorders/Vitamin_D-Dependent_Rickets_Type_2B.yaml:MG63 osteoblast-like HNRNPC perturbation model","model:kb/disorders/Vitamin_D-Dependent_Rickets_Type_2B.yaml:ROS 17/2.8 HNRNPC C1/C2 siRNA system"],"candidate_model_ids":["model:kb/disorders/Vitamin_D-Dependent_Rickets_Type_2B.yaml:Index-case EBV-transformed B-cell line"],"association_basis":"Same publication as a NAM (candidate)","nam_disease_context":"Same publication as a NAM (candidate)","source_paths":["kb/disorders/Vitamin_D-Dependent_Rickets_Type_2B.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Vitamin_D-Dependent_Rickets_Type_2B.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Vitamin_D-Dependent_Rickets_Type_2B.html#dataset-geo-gse22523"]},{"id":"dataset:geo:gse225435","accession":"GEO:GSE225435","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE225435","title":"RNA sequencing on Postnatal day (P) 7 wildtype and Zmiz1-Knockout cortex","alternate_titles":[],"description":"Cortical RNA-seq from the Emx1-Cre forebrain-specific Zmiz1 knockout, the primary transcriptomic dataset behind the \"Dysregulated Developmental Transcriptional Programs\" node. It identified 114 differentially expressed genes at postnatal day 7, with downregulated genes enriched for forebrain development, axon development, and neuron differentiation.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:16493","label":"ZMIZ1","display_label":"ZMIZ1","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/16493"}],"genes":["ZMIZ1"],"platforms":[],"platform":null,"publications":["PMID:41633496"],"publication_contexts":[{"context_id":"disorder:Neurodevelopmental_Disorder_with_Dysmorphic_Facies_and_Distal_Skeletal_Anomalies","publication":"PMID:41633496"}],"publication":"PMID:41633496","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41633496","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE225435","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE225435","reference_title":"RNA sequencing on Postnatal day (P) 7 wildtype and Zmiz1-Knockout cortex","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"We found 114 differentially expressed genes of which 35 genes were upregulated while 69 genes were downregulated. Downregulated genes were enriched in biological processes such as forebrain deveopment, axon development, neuron differentiation etc.","explanation":"Quantifies the transcriptional dysregulation asserted by the developmental-transcriptional-programs node, and names the enriched processes. The typo \"deveopment\" is present in the source record and is reproduced verbatim so the snippet validates."}],"notes":["Mouse cortex, not human tissue. No patient-derived transcriptomic dataset exists for this disorder, which is the calibration caveat recorded on the developmental-transcriptional-programs node."],"contexts":[{"id":"disorder:Neurodevelopmental_Disorder_with_Dysmorphic_Facies_and_Distal_Skeletal_Anomalies","name":"Neurodevelopmental Disorder with Dysmorphic Facies and Distal Skeletal Anomalies","kind":"Disorder","source_path":"kb/disorders/Neurodevelopmental_Disorder_with_Dysmorphic_Facies_and_Distal_Skeletal_Anomalies.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Neurodevelopmental_Disorder_with_Dysmorphic_Facies_and_Distal_Skeletal_Anomalies.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Neurodevelopmental_Disorder_with_Dysmorphic_Facies_and_Distal_Skeletal_Anomalies.html#dataset-geo-gse225435"}],"context_names":["Neurodevelopmental Disorder with Dysmorphic Facies and Distal Skeletal Anomalies"],"disease_names":["Neurodevelopmental Disorder with Dysmorphic Facies and Distal Skeletal Anomalies"],"disease_name":"Neurodevelopmental Disorder with Dysmorphic Facies and Distal Skeletal Anomalies","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Neurodevelopmental_Disorder_with_Dysmorphic_Facies_and_Distal_Skeletal_Anomalies.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Neurodevelopmental_Disorder_with_Dysmorphic_Facies_and_Distal_Skeletal_Anomalies.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Neurodevelopmental_Disorder_with_Dysmorphic_Facies_and_Distal_Skeletal_Anomalies.html#dataset-geo-gse225435"]},{"id":"dataset:geo:gse225460","accession":"geo:GSE225460","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE225460","title":"The Role of Interferon-γ in Autoimmune Polyendocrine Syndrome Type 1","alternate_titles":[],"description":"Background: Autoimmune polyendocrine syndrome type 1 (APS-1) is a life-threatening, autosomal recessive syndrome caused by autoimmune regulator (AIRE) deficiency. In APS-1, self-reactive T cells escape thymic negative selection, infiltrate organs, and drive autoimmune injury. The effector mechanisms governing T-cell-mediated damage in APS-1 remain poorly understood. Methods: We examined whether APS-1 could be classified as a disease mediated by interferon-γ. We first assessed patients with APS-1 who were participating in a prospective natural history study and evaluated mRNA and protein expression in blood and tissues.","alternate_descriptions":["Human bulk RNA-sequencing dataset of oral mucosal biopsies from people with APECED and healthy donors, including a pre/post-ruxolitinib series. It is directly relevant to the tissue interferon-γ/CXCL9 mechanism but is small and APS-1-specific."],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0003729","label":"mouth mucosa","display_label":"oral mucosal biopsy","url":"http://purl.obolibrary.org/obo/UBERON_0003729"}],"sample_type_labels":["mouth mucosa"],"sample_counts":[8],"sample_count":8,"conditions":["APECED oral mucosa","Healthy donor oral mucosa","Pre/post-ruxolitinib APS-1 tissue series"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:38810185"],"publication_contexts":[{"context_id":"disorder:Autoimmune_Polyendocrine_Syndrome_Type_1","publication":"PMID:38810185"},{"context_id":"disorder:Autoimmune_Polyendocrinopathy","publication":"PMID:38810185"}],"publication":"PMID:38810185","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38810185","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:38810185","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38810185","reference_title":"The Role of Interferon-γ in Autoimmune Polyendocrine Syndrome Type 1.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"Patients with APS-1 had enhanced interferon-γ responses in blood and in all examined autoimmunity-affected tissues.","explanation":"The associated publication supports transcriptomic interrogation of affected human tissues."}],"notes":["Identified by GEO DataSets index search for Autoimmune Polyendocrine Syndrome Type 1 (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.","https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE225460"],"contexts":[{"id":"disorder:Autoimmune_Polyendocrine_Syndrome_Type_1","name":"Autoimmune Polyendocrine Syndrome Type 1","kind":"Disorder","source_path":"kb/disorders/Autoimmune_Polyendocrine_Syndrome_Type_1.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autoimmune_Polyendocrine_Syndrome_Type_1.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autoimmune_Polyendocrine_Syndrome_Type_1.html#dataset-geo-gse225460"},{"id":"disorder:Autoimmune_Polyendocrinopathy","name":"Autoimmune Polyendocrinopathy","kind":"Disorder","source_path":"kb/disorders/Autoimmune_Polyendocrinopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autoimmune_Polyendocrinopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autoimmune_Polyendocrinopathy.html#dataset-geo-gse225460"}],"context_names":["Autoimmune Polyendocrine Syndrome Type 1","Autoimmune Polyendocrinopathy"],"disease_names":["Autoimmune Polyendocrine Syndrome Type 1","Autoimmune Polyendocrinopathy"],"disease_name":"Autoimmune Polyendocrine Syndrome Type 1","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Autoimmune_Polyendocrine_Syndrome_Type_1.yaml","kb/disorders/Autoimmune_Polyendocrinopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autoimmune_Polyendocrine_Syndrome_Type_1.yaml","https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autoimmune_Polyendocrinopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Autoimmune_Polyendocrine_Syndrome_Type_1.html#dataset-geo-gse225460","https://dismech.monarchinitiative.org/pages/disorders/Autoimmune_Polyendocrinopathy.html#dataset-geo-gse225460"]},{"id":"dataset:geo:gse225516","accession":"geo:GSE225516","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE225516","title":"Alternative splicing induced by bacterial pore-forming toxins sharpens CIRBP-mediated cell response to Listeria infection","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[18],"sample_count":18,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37941135"],"publication_contexts":[{"context_id":"disorder:Listeriosis","publication":"PMID:37941135"}],"publication":"PMID:37941135","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37941135","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:37941135","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/37941135","reference_title":"Alternative splicing induced by bacterial pore-forming toxins sharpens CIRBP-mediated cell response to Listeria infection.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"To gain isoform-level resolution of these modes of regulation, we combined long- and short-read transcriptomic analyses of the response of intestinal epithelial cells to infection by the foodborne pathogen Listeria monocytogenes.","explanation":"The linked publication states the assay and the host cells this dataset comes from."}],"notes":["Host transcriptional response to a pore-forming toxin, the class listeriolysin O belongs to. Relevant to the phagosome-escape node. Triaged as DIRECT by title."],"contexts":[{"id":"disorder:Listeriosis","name":"Listeriosis","kind":"Disorder","source_path":"kb/disorders/Listeriosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Listeriosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Listeriosis.html#dataset-geo-gse225516"}],"context_names":["Listeriosis"],"disease_names":["Listeriosis"],"disease_name":"Listeriosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Listeriosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Listeriosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Listeriosis.html#dataset-geo-gse225516"]},{"id":"dataset:geo:gse225949","accession":"geo:GSE225949","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE225949","title":"Rubella virus infection in endothelial cells reduces angiogenesis via interferon betainduced CXCL10","alternate_titles":[],"description":"Rubella virus infection during pregnancy can result in abortion, stillbirth and severe defects in embryogenesis resulting in congenital rubella syndrome (CRS). Low vaccination coverage in developing regions results in estimated 100,000 CRS cases in infants per year with a mortality rate over 30%. The molecular pathomechanisms and potential treatments remain largely unexplored. Endothelial cells (EC) of the placenta are infected by rubella virus (RuV). RuV reduced angiogenic and migratory capacity of primary human EC whereas cell cycle and apoptosis rate were not affected.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[19],"sample_count":19,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Rubella (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Rubella","name":"Rubella","kind":"Disorder","source_path":"kb/disorders/Rubella.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rubella.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Rubella.html#dataset-geo-gse225949"}],"context_names":["Rubella"],"disease_names":["Rubella"],"disease_name":"Rubella","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Rubella.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rubella.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Rubella.html#dataset-geo-gse225949"]},{"id":"dataset:geo:gse226019","accession":"geo:GSE226019","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE226019","title":"Restored glyoxylate metabolism in induced-hepatocytes after CRISPR/Cas-mediated AGXT gene correction and direct cell reprogramming of Primary Hyperoxaluria Type 1 fibroblasts","alternate_titles":[],"description":"Primary Hyperoxaluria Type 1 (PH1) is a rare inherited metabolic disorder characterized by oxalate overproduction in the liver, resulting in renal damage. It is caused by mutations in the AGXT gene. Combined liver and kidney transplantation is currently the only permanent curative treatment. We combined locus-specific gene correction and hepatic direct cell reprogramming to generate autologous healthy induced hepatocytes (iHeps) from PH1 patient-derived fibroblasts.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[39],"sample_count":39,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:38577102"],"publication_contexts":[{"context_id":"disorder:Primary_Hyperoxaluria_Type_1","publication":"PMID:38577102"}],"publication":"PMID:38577102","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38577102","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Primary Hyperoxaluria Type 1 (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Primary_Hyperoxaluria_Type_1","name":"Primary Hyperoxaluria Type 1","kind":"Disorder","source_path":"kb/disorders/Primary_Hyperoxaluria_Type_1.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Primary_Hyperoxaluria_Type_1.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Hyperoxaluria_Type_1.html#dataset-geo-gse226019"}],"context_names":["Primary Hyperoxaluria Type 1"],"disease_names":["Primary Hyperoxaluria Type 1"],"disease_name":"Primary Hyperoxaluria Type 1","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Primary_Hyperoxaluria_Type_1.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Primary_Hyperoxaluria_Type_1.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Primary_Hyperoxaluria_Type_1.html#dataset-geo-gse226019"]},{"id":"dataset:geo:gse226204","accession":"geo:GSE226204","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE226204","title":"Neurological Cockayne Syndrome Results from R-Loops Induced by Stalled RNA Polymerase II during Transcription Elongation","alternate_titles":[],"description":"Mutations in the Cockayne Syndrome group B (CSB) gene cause severe neurodevelopmental defects and premature aging. As a member of the SWI/SNF family of chromatin remodelers, CSB is best known for its role in transcription-coupled nucleotide excision (TC-NER), but this function neither explains the major disease phenotype nor offers any clue about the selective vulnerability in neurons. Pursuing Cockayne Syndrome-associated genome instability, we uncover an intrinsic mechanism by which elongating RNA polymerase II (RNAPII) undergoes transient pausing at internal T-runs where CSB is required to push RNAPII forward.","alternate_descriptions":[],"data_types":["MULTI_OMICS"],"data_type_labels":["Multi Omics"],"data_type_label":"Multi Omics","organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[37],"sample_count":37,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39019869"],"publication_contexts":[{"context_id":"disorder:Cockayne_Syndrome","publication":"PMID:39019869"}],"publication":"PMID:39019869","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39019869","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Cockayne Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Cockayne_Syndrome","name":"Cockayne Syndrome","kind":"Disorder","source_path":"kb/disorders/Cockayne_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cockayne_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cockayne_Syndrome.html#dataset-geo-gse226204"}],"context_names":["Cockayne Syndrome"],"disease_names":["Cockayne Syndrome"],"disease_name":"Cockayne Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cockayne_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cockayne_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cockayne_Syndrome.html#dataset-geo-gse226204"]},{"id":"dataset:geo:gse226303","accession":"geo:GSE226303","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE226303","title":"Characterisation of the sensory phenotype of the oesophageal mucosa in gastroesophageal reflux disease","alternate_titles":[],"description":"Identification of Novel Immune Cell Signature in Gastroesophageal Reflux Disease: Altered Mucosal Mast Cells and Dendritic Cell Profile. The mechanisms underlying the most troublesome symptom of gastroesophageal reflux disease (GERD), heartburn, remain incompletely understood. The pathogenesis of heartburn in GERD is likely to involve not only central mechanisms of sensitization including hypervigilance, but also multiple mucosal factors including maintenance of epithelial barrier integrity via tight junction proteins, expression of acid-sensing ion channels on nerve endings, and mucosal inflammation .","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[46],"sample_count":46,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:38098488"],"publication_contexts":[{"context_id":"disorder:Gastroesophageal_Reflux_Disease","publication":"PMID:38098488"}],"publication":"PMID:38098488","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38098488","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Gastroesophageal Reflux Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Gastroesophageal_Reflux_Disease","name":"Gastroesophageal Reflux Disease","kind":"Disorder","source_path":"kb/disorders/Gastroesophageal_Reflux_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Gastroesophageal_Reflux_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Gastroesophageal_Reflux_Disease.html#dataset-geo-gse226303"}],"context_names":["Gastroesophageal Reflux Disease"],"disease_names":["Gastroesophageal Reflux Disease"],"disease_name":"Gastroesophageal Reflux Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Gastroesophageal_Reflux_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Gastroesophageal_Reflux_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Gastroesophageal_Reflux_Disease.html#dataset-geo-gse226303"]},{"id":"dataset:geo:gse226338","accession":"geo:GSE226338","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE226338","title":"Gene expression of human angiosarcoma","alternate_titles":[],"description":"Gene expression profiling of human angiosarcoma samples was performed using the NanoString Human nCounter PanCancer IO 360 Panel","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[67],"sample_count":67,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37106027"],"publication_contexts":[{"context_id":"disorder:Angiosarcoma","publication":"PMID:37106027"}],"publication":"PMID:37106027","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37106027","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Angiosarcoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Angiosarcoma","name":"Angiosarcoma","kind":"Disorder","source_path":"kb/disorders/Angiosarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Angiosarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Angiosarcoma.html#dataset-geo-gse226338"}],"context_names":["Angiosarcoma"],"disease_names":["Angiosarcoma"],"disease_name":"Angiosarcoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Angiosarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Angiosarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Angiosarcoma.html#dataset-geo-gse226338"]},{"id":"dataset:geo:gse226646","accession":"geo:GSE226646","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE226646","title":"Skeletal muscle transcriptomics dissects the pathogenesis of Friedreich's Ataxia","alternate_titles":[],"description":"Bulk RNA sequencing of skeletal muscle biopsies from FRDA patients and healthy controls, sampled before and after recombinant human erythropoietin treatment, profiling the muscle transcriptome in patient tissue.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[20],"sample_count":20,"conditions":["Friedreich ataxia skeletal muscle","healthy control skeletal muscle"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37027192"],"publication_contexts":[{"context_id":"disorder:Friedreich_Ataxia","publication":"PMID:37027192"}],"publication":"PMID:37027192","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37027192","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE226646","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE226646","reference_title":"Skeletal muscle transcriptomics dissects the pathogenesis of Friedreich's Ataxia","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"RNA sequencing of skeletal muscle biopsies from healthy controls and Friedreich's Ataxia (FRDA) patients before and after treatment with recombinant human erythropoietin (rhuEPO) to dissect the mechanisms of disease.","explanation":"The GEO summary establishes this as a patient-versus-control skeletal muscle transcriptome series in FRDA."}],"notes":[],"contexts":[{"id":"disorder:Friedreich_Ataxia","name":"Friedreich Ataxia","kind":"Disorder","source_path":"kb/disorders/Friedreich_Ataxia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Friedreich_Ataxia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Friedreich_Ataxia.html#dataset-geo-gse226646"}],"context_names":["Friedreich Ataxia"],"disease_names":["Friedreich Ataxia"],"disease_name":"Friedreich Ataxia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Friedreich_Ataxia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Friedreich_Ataxia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Friedreich_Ataxia.html#dataset-geo-gse226646"]},{"id":"dataset:geo:gse226808","accession":"geo:GSE226808","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE226808","title":"Different immunological mechanisms between AQP4-positive and MOG-positive optic neuritis based on RNA-seq analysis of whole blood","alternate_titles":[],"description":"To compare the different immunological mechanisms between aquaporin 4 antibody-associated optic neuritis (AQP4-ON) and myelin oligodendrocyte glycoprotein antibody-associated optic neuritis (MOG-ON) based on RNA sequencing (RNA-seq) of whole blood.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[21],"sample_count":21,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:36969199"],"publication_contexts":[{"context_id":"disorder:MOGAD","publication":"PMID:36969199"},{"context_id":"disorder:Optic_Neuritis","publication":"PMID:36969199"}],"publication":"PMID:36969199","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36969199","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for MOGAD (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.","Identified by GEO DataSets index search for Optic Neuritis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:MOGAD","name":"MOGAD","kind":"Disorder","source_path":"kb/disorders/MOGAD.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MOGAD.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/MOGAD.html#dataset-geo-gse226808"},{"id":"disorder:Optic_Neuritis","name":"Optic Neuritis","kind":"Disorder","source_path":"kb/disorders/Optic_Neuritis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Optic_Neuritis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Optic_Neuritis.html#dataset-geo-gse226808"}],"context_names":["MOGAD","Optic Neuritis"],"disease_names":["MOGAD","Optic Neuritis"],"disease_name":"MOGAD","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/MOGAD.yaml","kb/disorders/Optic_Neuritis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MOGAD.yaml","https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Optic_Neuritis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/MOGAD.html#dataset-geo-gse226808","https://dismech.monarchinitiative.org/pages/disorders/Optic_Neuritis.html#dataset-geo-gse226808"]},{"id":"dataset:geo:gse227124","accession":"geo:GSE227124","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE227124","title":"Plasma cell infiltrate populating the muscle tissue of patients with inclusion body myositis feature distinct BCR repertoire properties","alternate_titles":[],"description":"Inclusion body myositis (IBM) is an autoimmune and degenerative disorder of skeletal muscle. The B cell infiltrates in IBM muscle tissue are predominantly fully differentiated antibody-secreting plasma cells, with scarce naïve or memory B cells. The role of this infiltrate in the disease pathology is not well understood. To better define the humoral response in IBM, we used adaptive immune receptor repertoire sequencing to generate large B cell receptor (BCR) repertoire libraries from IBM muscle biopsies and compared them to those generated from dermatomyositis (DM), polymyositis (PM), and circulating CD27+ memory B cells, derived from healthy controls and antibody secreting cells (ASC) coll...","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[10],"sample_count":10,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37171806"],"publication_contexts":[{"context_id":"disorder:Inclusion_Body_Myositis","publication":"PMID:37171806"}],"publication":"PMID:37171806","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37171806","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Inclusion Body Myositis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Inclusion_Body_Myositis","name":"Inclusion Body Myositis","kind":"Disorder","source_path":"kb/disorders/Inclusion_Body_Myositis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Inclusion_Body_Myositis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Inclusion_Body_Myositis.html#dataset-geo-gse227124"}],"context_names":["Inclusion Body Myositis"],"disease_names":["Inclusion Body Myositis"],"disease_name":"Inclusion Body Myositis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Inclusion_Body_Myositis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Inclusion_Body_Myositis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Inclusion_Body_Myositis.html#dataset-geo-gse227124"]},{"id":"dataset:geo:gse227299","accession":"geo:GSE227299","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE227299","title":"Small noncoding RNA Dysregulation is Implicated in Manganism in a Rat Model of Methylcyclopentadienyl Manganese Tricarbonyl-Induced Unrepaired Striatum Damage","alternate_titles":[],"description":"Excessive accumulation of manganese in brain can cause Parkinsonian-like symptoms, known as Manganism. Methylcyclopentadienyl Manganese Tricarbonyl (MMT), a gasoline antiknock additive, is one of environmental exposures of manganese, which can lead to manganism in Rats. Though some researches showed that small non-coding RNAs (sncRNAs) were differently expressed in Parkinson’s disease (PD) patients, it was still unclear whether and how sncRNAs dysfunction appeared in Manganism.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10116","label":"Rattus norvegicus","display_label":"rat","url":"http://purl.obolibrary.org/obo/NCBITaxon_10116"}],"organism_labels":["Rattus norvegicus"],"organism_label":"Rattus norvegicus","sample_types":[],"sample_type_labels":[],"sample_counts":[9],"sample_count":9,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Manganism (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Manganism","name":"Manganism","kind":"Disorder","source_path":"kb/disorders/Manganism.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Manganism.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Manganism.html#dataset-geo-gse227299"}],"context_names":["Manganism"],"disease_names":["Manganism"],"disease_name":"Manganism","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Manganism.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Manganism.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Manganism.html#dataset-geo-gse227299"]},{"id":"dataset:geo:gse227375","accession":"geo:GSE227375","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE227375","title":"Sex-Dependent Transcriptional Changes in response to stress in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome","alternate_titles":[],"description":"Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, multi-symptom illness characterized by debilitating fatigue and post-exertional malaise (PEM). Numerous studies have reported sex differences at the epidemiological, cellular, and molecular levels between male and female ME/CFS patients. To gain further insight into these sex-dependent changes, we evaluated differential gene expression by RNA-sequencing in 35 ME/CFS patients (24 female, 11 male) and 34 matched healthy control participants (21 female and 13 male) during and after an exercise challenge intended to provoke PEM.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[187],"sample_count":187,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37373402"],"publication_contexts":[{"context_id":"disorder:Myalgic_Encephalomyelitis_Chronic_Fatigue_Syndrome","publication":"PMID:37373402"}],"publication":"PMID:37373402","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37373402","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values. Accession reverified on 2026-09-04. Dataset records or repeated samples are not necessarily independent participants. Provider-report citation does not establish that OpenScientist downloaded or analyzed this dataset."],"contexts":[{"id":"disorder:Myalgic_Encephalomyelitis_Chronic_Fatigue_Syndrome","name":"Myalgic Encephalomyelitis/Chronic Fatigue Syndrome","kind":"Disorder","source_path":"kb/disorders/Myalgic_Encephalomyelitis_Chronic_Fatigue_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myalgic_Encephalomyelitis_Chronic_Fatigue_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Myalgic_Encephalomyelitis_Chronic_Fatigue_Syndrome.html#dataset-geo-gse227375"}],"context_names":["Myalgic Encephalomyelitis/Chronic Fatigue Syndrome"],"disease_names":["Myalgic Encephalomyelitis/Chronic Fatigue Syndrome"],"disease_name":"Myalgic Encephalomyelitis/Chronic Fatigue 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Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Atrial_Fibrillation","name":"Atrial Fibrillation","kind":"Disorder","source_path":"kb/disorders/Atrial_Fibrillation.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Atrial_Fibrillation.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Atrial_Fibrillation.html#dataset-geo-gse227793"}],"context_names":["Atrial Fibrillation"],"disease_names":["Atrial Fibrillation"],"disease_name":"Atrial Fibrillation","same_context_model_ids":["model:kb/disorders/Atrial_Fibrillation.yaml:Palmitate-treated human iPSC-derived atrial cardiomyocytes"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Atrial_Fibrillation.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Atrial_Fibrillation.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Atrial_Fibrillation.html#dataset-geo-gse227793"]},{"id":"dataset:geo:gse227835","accession":"geo:GSE227835","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE227835","title":"Single-cell RNA-seq data of human PBMC from Myasthenia Gravis patients","alternate_titles":[],"description":"Myasthenia Gravis (MG) is a chronic autoimmune disorder characterized by severe muscle weakness. However, the seronegative MG patient subgroup, which accounts for about 15% of MG patients, remains challenging diagnosis, and the immunopathology is understudied. Therefore, we performed single-cell RNA-sequencing analysis by peripheral blood and plasma proteome analysis for the seronegative MG patients. Numerical abnormalities were observed in multiple immune cells including B-cells compared to healthy controls (HC) and correlated with disease activities.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[40],"sample_count":40,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:38711503"],"publication_contexts":[{"context_id":"disorder:Myasthenia_Gravis","publication":"PMID:38711503"}],"publication":"PMID:38711503","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38711503","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Myasthenia Gravis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Myasthenia_Gravis","name":"Myasthenia Gravis","kind":"Disorder","source_path":"kb/disorders/Myasthenia_Gravis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myasthenia_Gravis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Myasthenia_Gravis.html#dataset-geo-gse227835"}],"context_names":["Myasthenia Gravis"],"disease_names":["Myasthenia Gravis"],"disease_name":"Myasthenia Gravis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Myasthenia_Gravis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myasthenia_Gravis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Myasthenia_Gravis.html#dataset-geo-gse227835"]},{"id":"dataset:geo:gse228205","accession":"geo:GSE228205","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE228205","title":"Effect of endovascular treatment on gene expression in patients with Budd-Chiari syndrome","alternate_titles":[],"description":"Budd-Chiari syndrome (BCS) results in sinusoidal congestion and hepatocyte apoptosis, which can further progress to liver fibrosis, cirrhosis, and hepatocellular carcinoma. Endovascular (EV) treatment has been the primary therapeutic method and achieved excellent outcomes. However, whether EV treatment could reverse liver cirrhosis in patients with BCS is still unclear. To investigate the effect of endovascular treatment on liver cirrhosis in patients with Budd-Chiari syndrome, we performed gene expression profiling analysis of the liver from patients with or without EV treatment.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[8],"sample_count":8,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Budd-Chiari Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Budd-Chiari_Syndrome","name":"Budd-Chiari Syndrome","kind":"Disorder","source_path":"kb/disorders/Budd-Chiari_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Budd-Chiari_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Budd-Chiari_Syndrome.html#dataset-geo-gse228205"}],"context_names":["Budd-Chiari Syndrome"],"disease_names":["Budd-Chiari Syndrome"],"disease_name":"Budd-Chiari Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Budd-Chiari_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Budd-Chiari_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Budd-Chiari_Syndrome.html#dataset-geo-gse228205"]},{"id":"dataset:geo:gse228390","accession":"geo:GSE228390","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE228390","title":"Lack of strong innate immune reactivity renders macrophages alone unable to control productive Varicella-Zoster Virus infection in an isogenic human iPSC-derived neuronal co-culture model.","alternate_titles":[],"description":"Bulk RNA-seq of iPSC-derived neuron-macrophage co-cultures infected with VZV. 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Relevant to understanding why VZV establishes latency despite innate immune surveillance."],"contexts":[{"id":"disorder:Chickenpox","name":"Chickenpox","kind":"Disorder","source_path":"kb/disorders/Chickenpox.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chickenpox.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chickenpox.html#dataset-geo-gse228390"}],"context_names":["Chickenpox"],"disease_names":["Chickenpox"],"disease_name":"Chickenpox","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chickenpox.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chickenpox.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chickenpox.html#dataset-geo-gse228390"]},{"id":"dataset:geo:gse228411","accession":"geo:GSE228411","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE228411","title":"Effect of epithelial depletion of Wnt10a on gene expression alteration during tooth root furcation development","alternate_titles":[],"description":"Bulk RNA-seq of molar epithelium from furcation region after epithelial Wnt10a ablation, directly probing molecular programs linked to taurodontism-like root furcation defects.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[{"id":"CL:0000066","label":"epithelial cell","display_label":"epithelial cell","url":"http://purl.obolibrary.org/obo/CL_0000066"}],"sample_type_labels":["epithelial cell"],"sample_counts":[6],"sample_count":6,"conditions":["K14-Cre;Wnt10aflox/flox","Wnt10aflox/flox control"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["GPL24247"],"platform":"GPL24247","publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE228411","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE228411","reference_title":"Effect of epithelial depletion of Wnt10a on gene expression alteration during tooth root furcation development","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"In our previous study, the knockout of Wnt10a in dental epithelium resulted in the occurrence of taurodontism and root furcation defects, suggesting that epithelial Wnt10a was a pivotal signal to guide root furcation patterning.","explanation":"Directly links this dataset to taurodontism-relevant root furcation biology."}],"notes":[],"contexts":[{"id":"disorder:Taurodontism","name":"Taurodontism","kind":"Disorder","source_path":"kb/disorders/Taurodontism.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Taurodontism.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Taurodontism.html#dataset-geo-gse228411"}],"context_names":["Taurodontism"],"disease_names":["Taurodontism"],"disease_name":"Taurodontism","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Taurodontism.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Taurodontism.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Taurodontism.html#dataset-geo-gse228411"]},{"id":"dataset:geo:gse228522","accession":"geo:GSE228522","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE228522","title":"Transcriptomic differences underlying the Activin-A induced large osteoclast formation in both healthy control and Fibrodysplasia Ossificans Progressiva osteoclasts","alternate_titles":[],"description":"Activin-A has been identified as the driver for heterotopic ossification in FOP. It's effect on osteoclast formation is not extensively studied in control or FOP samples.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[24],"sample_count":24,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37047804"],"publication_contexts":[{"context_id":"disorder:Fibrodysplasia_Ossificans_Progressiva","publication":"PMID:37047804"}],"publication":"PMID:37047804","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37047804","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Fibrodysplasia Ossificans Progressiva (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Fibrodysplasia_Ossificans_Progressiva","name":"Fibrodysplasia Ossificans Progressiva","kind":"Disorder","source_path":"kb/disorders/Fibrodysplasia_Ossificans_Progressiva.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fibrodysplasia_Ossificans_Progressiva.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Fibrodysplasia_Ossificans_Progressiva.html#dataset-geo-gse228522"}],"context_names":["Fibrodysplasia Ossificans Progressiva"],"disease_names":["Fibrodysplasia Ossificans Progressiva"],"disease_name":"Fibrodysplasia Ossificans Progressiva","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Fibrodysplasia_Ossificans_Progressiva.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fibrodysplasia_Ossificans_Progressiva.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Fibrodysplasia_Ossificans_Progressiva.html#dataset-geo-gse228522"]},{"id":"dataset:geo:gse228566","accession":"geo:GSE228566","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE228566","title":"Nr2f1 shapes mitochondria in the mouse brain unraveling novel insights into the neurodevelopmental disorder BBSOAS","alternate_titles":[],"description":"Mouse-cortex COUP-TFI/NR2F1 chromatin immunoprecipitation sequencing with IgG and H3K4me3 comparators, used to identify candidate direct nuclear-encoded mitochondrial targets in a BBSOAS mechanism study.","alternate_descriptions":[],"data_types":["CHIP_SEQ"],"data_type_labels":["Chromatin immunoprecipitation sequencing"],"data_type_label":"Chromatin immunoprecipitation sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[{"id":"UBERON:0000956","label":"cerebral cortex","display_label":"cerebral cortex","url":"http://purl.obolibrary.org/obo/UBERON_0000956"}],"sample_type_labels":["cerebral cortex"],"sample_counts":[],"sample_count":null,"conditions":["COUP-TFI chromatin immunoprecipitation in mouse cortex","IgG control in mouse cortex","H3K4me3 chromatin immunoprecipitation in mouse cortex"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37260288"],"publication_contexts":[{"context_id":"disorder:Bosch-Boonstra-Schaaf_Optic_Atrophy_Syndrome","publication":"PMID:37260288"}],"publication":"PMID:37260288","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37260288","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"url:https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE228566","reference_url":null,"reference_title":"GEO Accession viewer","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"Coup-TF1_Cortex","explanation":"The GEO series lists the COUP-TFI mouse-cortex chromatin sample deposited under GSE228566; its adjacent series records provide the IgG and H3K4me3 comparators described in the conditions."}],"notes":[],"contexts":[{"id":"disorder:Bosch-Boonstra-Schaaf_Optic_Atrophy_Syndrome","name":"Bosch-Boonstra-Schaaf Optic Atrophy Syndrome","kind":"Disorder","source_path":"kb/disorders/Bosch-Boonstra-Schaaf_Optic_Atrophy_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bosch-Boonstra-Schaaf_Optic_Atrophy_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Bosch-Boonstra-Schaaf_Optic_Atrophy_Syndrome.html#dataset-geo-gse228566"}],"context_names":["Bosch-Boonstra-Schaaf Optic Atrophy Syndrome"],"disease_names":["Bosch-Boonstra-Schaaf Optic Atrophy Syndrome"],"disease_name":"Bosch-Boonstra-Schaaf Optic Atrophy Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Bosch-Boonstra-Schaaf_Optic_Atrophy_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bosch-Boonstra-Schaaf_Optic_Atrophy_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Bosch-Boonstra-Schaaf_Optic_Atrophy_Syndrome.html#dataset-geo-gse228566"]},{"id":"dataset:geo:gse229366","accession":"geo:GSE229366","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE229366","title":"PCDH19 regulation of neural progenitor cell differentiation suggests asynchrony of neurogenesis as a mechanism contributing to PCDH19 Girls Clustering Epilepsy","alternate_titles":[],"description":"Expression arrays on cultured neurospheres from Pcdh19 knockout, wild-type, and a mosaic mix of the two genotypes, at day 0 and day 4 of differentiation. The mosaic arm is what makes this series unusual: most PCDH19 model data compare null to wild type, but the disease is female-limited precisely because affected brains are mosaic, so a three-way design is the one that can separate an interference effect from a cell-autonomous one.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"house mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[18],"sample_count":18,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:14270","label":"PCDH19","display_label":"PCDH19","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/14270"}],"genes":["PCDH19"],"platforms":[],"platform":null,"publications":["PMID:29763708"],"publication_contexts":[{"context_id":"disorder:PCDH19_Clustering_Epilepsy","publication":"PMID:29763708"}],"publication":"PMID:29763708","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/29763708","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Found by a targeted GEO DataSets title search for PCDH19; accession and metadata verified against NCBI E-utilities on 2026-08-27, design re-verified on 2026-09-12. Title, sample count, and organism are GEO's own values. Model-organism data - the gene descriptor is the human HGNC record for the disease gene.\n\nThe three-genotype design is GEO's own, not inferred. GEO's \"Overall design\" field for the series reads: \"Cultured neurospheres from Pcdh19 knock out, wild type or a mosaic mix of cells, from these two genotypes compared at day 0 and day 4 of differentiation. Three technical replicates per genotype and per timepoint were measured.\" The 18 samples are named accordingly: \"neurosphere_wild_type_1..3\" (GSM7159328-30), \"neurosphere_Pcdh19_knockout_1..3\" (GSM7159331-33), \"neurosphere_mosaic_wild_type-Pcdh19_knockout_1..3\" (GSM7159334-36), and the same three arms again as \"differentiated_neurosphere_*\" (GSM7159337-45). The design field and sample titles were read from the live GEO record on 2026-09-15. The cached GEO record (references_cache/GEO_GSE229366.md) holds only GEO's title and summary, and that summary is the 2018 abstract, which describes only the knockout-versus-control comparison, so the mosaic arm cannot be quoted from the cache as a snippet and is recorded here instead.\n\nGEO lists no linked PMID, and the accession sits in the 2023 submission range while PMID:29763708 is a 2018 paper. The linkage is nonetheless sound: the series carries that paper's title and its summary is that paper's abstract verbatim. The gap is a late deposit of data from an already-published study, not a mismatched record."],"contexts":[{"id":"disorder:PCDH19_Clustering_Epilepsy","name":"PCDH19 Clustering Epilepsy","kind":"Disorder","source_path":"kb/disorders/PCDH19_Clustering_Epilepsy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/PCDH19_Clustering_Epilepsy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/PCDH19_Clustering_Epilepsy.html#dataset-geo-gse229366"}],"context_names":["PCDH19 Clustering Epilepsy"],"disease_names":["PCDH19 Clustering Epilepsy"],"disease_name":"PCDH19 Clustering Epilepsy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/PCDH19_Clustering_Epilepsy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/PCDH19_Clustering_Epilepsy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/PCDH19_Clustering_Epilepsy.html#dataset-geo-gse229366"]},{"id":"dataset:geo:gse229527","accession":"geo:GSE229527","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE229527","title":"RNA-seq analysis of hilar and peripheral biliary organoids from a mouse model of Alagille syndrome","alternate_titles":[],"description":"To study molecular differences in wild-type and regenrated bile ducts in a mouse model of Alagille syndrome (Andersson, Chivukula, Hankeova, et al. Gastroenterology, 2018;154(4):1080-1095), we derived intrahepatic cholangiocyte organoids from hilar (pICOs) and peripheral (pICOs) regions of adult livers following a published protocol for organoids derivation and culture (Broutier et al., Nat Protoc. 2016;11:1724–1743). At passage 5, we isolated total RNA and performed bulk RNA-sequencing on 3 biological replicates from each region and genotype.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:38014627"],"publication_contexts":[{"context_id":"disorder:Alagille_syndrome","publication":"PMID:38014627"}],"publication":"PMID:38014627","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38014627","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Alagille syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Alagille_syndrome","name":"Alagille syndrome","kind":"Disorder","source_path":"kb/disorders/Alagille_syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alagille_syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Alagille_syndrome.html#dataset-geo-gse229527"}],"context_names":["Alagille syndrome"],"disease_names":["Alagille syndrome"],"disease_name":"Alagille syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Alagille_syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alagille_syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Alagille_syndrome.html#dataset-geo-gse229527"]},{"id":"dataset:geo:gse229528","accession":"geo:GSE229528","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE229528","title":"Small RNA-seq of chronic pancreatitis patient plasma samples","alternate_titles":[],"description":"The purpose of our study was to identify miRNAs that can predict islet transplantation outcomes. We hypothesize that miRNAs may be used to predict islet function post-transplantation in TPIAT patients","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[24],"sample_count":24,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Chronic Pancreatitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Chronic_Pancreatitis","name":"Chronic Pancreatitis","kind":"Disorder","source_path":"kb/disorders/Chronic_Pancreatitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Pancreatitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chronic_Pancreatitis.html#dataset-geo-gse229528"}],"context_names":["Chronic Pancreatitis"],"disease_names":["Chronic Pancreatitis"],"disease_name":"Chronic Pancreatitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chronic_Pancreatitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Pancreatitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chronic_Pancreatitis.html#dataset-geo-gse229528"]},{"id":"dataset:geo:gse229698","accession":"geo:GSE229698","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE229698","title":"TRAF7 is an essential regulator of vascular integrity","alternate_titles":[],"description":"RNA sequencing of developing mouse embryos after global or endothelial Traf7 deletion, used to assess altered gene expression and the vascular-integrity hypothesis. This is model-organism transcriptomics, not the human syndrome fibroblast dataset.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37583551"],"publication_contexts":[{"context_id":"disorder:Cardiac_Facial_And_Digital_Anomalies_With_Developmental_Delay","publication":"PMID:37583551"}],"publication":"PMID:37583551","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37583551","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE229698","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE229698","reference_title":"TRAF7 is an essential regulator of vascular integrity","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"Objective: to present first in vivo experimental evidence of TRAF7 function by using global and endothelium-specific TRAF7 knockout mice and comparing transcriptomes of developing embryos.","explanation":"Fetched GEO summary confirms the study identity and experimental context."}],"notes":[],"contexts":[{"id":"disorder:Cardiac_Facial_And_Digital_Anomalies_With_Developmental_Delay","name":"Cardiac, Facial, and Digital Anomalies with Developmental Delay","kind":"Disorder","source_path":"kb/disorders/Cardiac_Facial_And_Digital_Anomalies_With_Developmental_Delay.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cardiac_Facial_And_Digital_Anomalies_With_Developmental_Delay.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cardiac,_Facial,_and_Digital_Anomalies_with_Developmental_Delay.html#dataset-geo-gse229698"}],"context_names":["Cardiac, Facial, and Digital Anomalies with Developmental Delay"],"disease_names":["Cardiac, Facial, and Digital Anomalies with Developmental Delay"],"disease_name":"Cardiac, Facial, and Digital Anomalies with Developmental Delay","same_context_model_ids":["model:kb/disorders/Cardiac_Facial_And_Digital_Anomalies_With_Developmental_Delay.yaml:HEK293 TRAF7-IFT57 binding assay","model:kb/disorders/Cardiac_Facial_And_Digital_Anomalies_With_Developmental_Delay.yaml:TRAF7 syndrome patient fibroblasts"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Cardiac_Facial_And_Digital_Anomalies_With_Developmental_Delay.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cardiac_Facial_And_Digital_Anomalies_With_Developmental_Delay.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cardiac,_Facial,_and_Digital_Anomalies_with_Developmental_Delay.html#dataset-geo-gse229698"]},{"id":"dataset:geo:gse229968","accession":"geo:GSE229968","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE229968","title":"Gene expression of CD56positive and CD56negative human muscle stem cells from normal and Duchenne Muscular Dystrophy muscles","alternate_titles":[],"description":"In Duchenne Muscular Dystrophy (DMD), the absence of the subsarcolemmal dystrophin protein leads to repeated myofiber damages inducing cycles of muscle regeneration that is driven by muscle stem cells (MuSCs). With time, MuSC regenerative capacities are overwhelmed, leading to fibrosis and muscle atrophy. Whether MuSCs from DMD muscle have intrinsic alterations or are primed by their degenerative/regenerative environment is still debated. We investigated gene expression in human using primary MuSCs derived from DMD or healthy muscles.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39650736"],"publication_contexts":[{"context_id":"disorder:Duchenne_Muscular_Dystrophy","publication":"PMID:39650736"}],"publication":"PMID:39650736","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39650736","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Duchenne Muscular Dystrophy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Duchenne_Muscular_Dystrophy","name":"Duchenne Muscular Dystrophy","kind":"Disorder","source_path":"kb/disorders/Duchenne_Muscular_Dystrophy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Duchenne_Muscular_Dystrophy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Duchenne_Muscular_Dystrophy.html#dataset-geo-gse229968"}],"context_names":["Duchenne Muscular Dystrophy"],"disease_names":["Duchenne Muscular Dystrophy"],"disease_name":"Duchenne Muscular Dystrophy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Duchenne_Muscular_Dystrophy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Duchenne_Muscular_Dystrophy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Duchenne_Muscular_Dystrophy.html#dataset-geo-gse229968"]},{"id":"dataset:geo:gse230316","accession":"geo:GSE230316","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE230316","title":"DNA-guided transcription factor cooperativity shapes face and limb mesenchyme [ChIP-seq]","alternate_titles":[],"description":"ChIP-seq profiling of TWIST1 and homeodomain transcription factor occupancy in embryonic face and limb mesenchyme, defining the composite 'Coordinator' motif at which TWIST1 binds the E-box half cooperatively with homeodomain factors.","alternate_descriptions":[],"data_types":["CHIP_SEQ"],"data_type_labels":["Chromatin immunoprecipitation sequencing"],"data_type_label":"Chromatin immunoprecipitation sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[200],"sample_count":200,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:38262408"],"publication_contexts":[{"context_id":"disorder:Sweeney-Cox_Syndrome","publication":"PMID:38262408"}],"publication":"PMID:38262408","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38262408","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Selected manually from the mechanism literature, not from a gene-name dataset search — a TWIST1 accession search returns predominantly cancer EMT studies, which are irrelevant here. This dataset maps TWIST1 DNA occupancy in exactly the tissue affected in this syndrome, so it bears on the consequence of a basic-domain substitution. GEO lists both Homo sapiens and Mus musculus for the series; the human organism binding is recorded here."],"contexts":[{"id":"disorder:Sweeney-Cox_Syndrome","name":"Sweeney-Cox Syndrome","kind":"Disorder","source_path":"kb/disorders/Sweeney-Cox_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sweeney-Cox_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Sweeney-Cox_Syndrome.html#dataset-geo-gse230316"}],"context_names":["Sweeney-Cox Syndrome"],"disease_names":["Sweeney-Cox Syndrome"],"disease_name":"Sweeney-Cox Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Sweeney-Cox_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sweeney-Cox_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Sweeney-Cox_Syndrome.html#dataset-geo-gse230316"]},{"id":"dataset:geo:gse230696","accession":"geo:GSE230696","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE230696","title":"Multi-omics of Bohring-Opitz syndrome truncating ASXL1 mutations identify canonical and non-canonical Wnt signaling dysregulation","alternate_titles":[],"description":"Human primary-cell multi-omics dataset from Bohring-Opitz syndrome patients and controls, including peripheral blood and skin fibroblast assays used to study epigenomic dysregulation and Wnt signaling.","alternate_descriptions":[],"data_types":["MULTI_OMICS_PERTURBATION"],"data_type_labels":["Multi Omics Perturbation"],"data_type_label":"Multi Omics Perturbation","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0000178","label":"blood","display_label":"peripheral blood","url":"http://purl.obolibrary.org/obo/UBERON_0000178"},{"id":"CL:0002620","label":"skin fibroblast","display_label":"skin fibroblast","url":"http://purl.obolibrary.org/obo/CL_0002620"}],"sample_type_labels":["blood","skin fibroblast"],"sample_counts":[67],"sample_count":67,"conditions":["Bohring-Opitz syndrome","control"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37053013"],"publication_contexts":[{"context_id":"disorder:Bohring-Opitz_syndrome","publication":"PMID:37053013"}],"publication":"PMID:37053013","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37053013","publication_status":"Publication recorded","findings":[{"statement":"Patient-derived primary cells from BOS and controls reveal cross-tissue epigenomic disruption and Wnt signaling dysregulation.","evidence":[{"reference":"PMID:37053013","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/37053013","reference_title":"Multiomics of Bohring-Opitz syndrome truncating ASXL1 mutations identify canonical and noncanonical Wnt signaling dysregulation.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We used primary cells from individuals with BOS (n = 18) and controls (n = 49) to dissect gene regulatory changes caused by ASXL1 mutations using comprehensive multiomics assays for chromatin accessibility (ATAC-seq), DNA methylation, histone methylation binding, and transcriptome in peripheral blood and skin fibroblasts.","explanation":"This supports the dataset as a human primary-cell BOS resource for mechanistic epigenomic analysis."},{"reference":"PMID:37053013","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/37053013","reference_title":"Multiomics of Bohring-Opitz syndrome truncating ASXL1 mutations identify canonical and noncanonical Wnt signaling dysregulation.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Our data show that regardless of cell type, ASXL1 mutations drive strong cross-tissue effects that disrupt multiple layers of the epigenome.","explanation":"This supports the dataset as a primary-cell BOS resource for multi-omics epigenomic analysis."}]}],"findings_text":["Patient-derived primary cells from BOS and controls reveal cross-tissue epigenomic disruption and Wnt signaling dysregulation."],"evidence":[{"reference":"PMID:37053013","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/37053013","reference_title":"Multiomics of Bohring-Opitz syndrome truncating ASXL1 mutations identify canonical and noncanonical Wnt signaling dysregulation.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We used primary cells from individuals with BOS (n = 18) and controls (n = 49) to dissect gene regulatory changes caused by ASXL1 mutations using comprehensive multiomics assays for chromatin accessibility (ATAC-seq), DNA methylation, histone methylation binding, and transcriptome in peripheral blood and skin fibroblasts.","explanation":"This directly supports the cohort size, specimen types, and multi-omics content represented by GSE230696."},{"reference":"PMID:37053013","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/37053013","reference_title":"Multiomics of Bohring-Opitz syndrome truncating ASXL1 mutations identify canonical and noncanonical Wnt signaling dysregulation.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Our data show that regardless of cell type, ASXL1 mutations drive strong cross-tissue effects that disrupt multiple layers of the epigenome.","explanation":"This supports the dataset as a primary-cell BOS resource for multi-omics epigenomic analysis."}],"notes":["The reported total comprises 18 individuals with BOS and 49 controls; assay-specific sample sizes differ, and only four affected individuals contributed both blood and fibroblast specimens."],"contexts":[{"id":"disorder:Bohring-Opitz_syndrome","name":"Bohring-Opitz syndrome","kind":"Disorder","source_path":"kb/disorders/Bohring-Opitz_syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bohring-Opitz_syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Bohring-Opitz_syndrome.html#dataset-geo-gse230696"}],"context_names":["Bohring-Opitz syndrome"],"disease_names":["Bohring-Opitz syndrome"],"disease_name":"Bohring-Opitz syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Bohring-Opitz_syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bohring-Opitz_syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Bohring-Opitz_syndrome.html#dataset-geo-gse230696"]},{"id":"dataset:geo:gse230731","accession":"geo:GSE230731","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE230731","title":"The role of serum miRs in IgA nephropathy","alternate_titles":[],"description":"To ascetain whether a serum miR signature can distinguish patients with progressive IgAN from the stable form and to determine the signature specificity for IgAN by comparing serum miR profiles with subjects with membranous nephropathy and healthy subjects.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[40],"sample_count":40,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40268167"],"publication_contexts":[{"context_id":"disorder:IgA_Nephropathy","publication":"PMID:40268167"}],"publication":"PMID:40268167","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40268167","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for IgA Nephropathy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:IgA_Nephropathy","name":"IgA Nephropathy","kind":"Disorder","source_path":"kb/disorders/IgA_Nephropathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/IgA_Nephropathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/IgA_Nephropathy.html#dataset-geo-gse230731"}],"context_names":["IgA Nephropathy"],"disease_names":["IgA Nephropathy"],"disease_name":"IgA Nephropathy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/IgA_Nephropathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/IgA_Nephropathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/IgA_Nephropathy.html#dataset-geo-gse230731"]},{"id":"dataset:geo:gse231432","accession":"geo:GSE231432","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE231432","title":"HSC-derived exosomal miR-122- 5p inhibits EMT and fibrosis of intrahepatic biliary epithelial cells to alleviate primary biliary cholangitis","alternate_titles":[],"description":"Objective: The objective was to study the expression profile of serum exosomal ncRNAs in patients with PBC and to explore their potential molecular mechanisms. Methods: The expression profile of ncRNAs in serum exosomes of PBC patients was analyzed by RNA-sequence. Bioinformatics analysis predicted target genes and related signaling pathways. Spearson correlation analysis and receiver operating characteristic (ROC) curve were used to explore the relationship between ncRNAs and PBC clinical indicators and application value. Primary human intrahepatic biliary epithelial cells (HIBECs) were cultured in vitro and lipopolysaccharide (LPS) induced HIBECs inflammatory injury model.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[24],"sample_count":24,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41246340"],"publication_contexts":[{"context_id":"disorder:Primary_Biliary_Cholangitis","publication":"PMID:41246340"}],"publication":"PMID:41246340","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41246340","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Primary Biliary Cholangitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Primary_Biliary_Cholangitis","name":"Primary Biliary Cholangitis","kind":"Disorder","source_path":"kb/disorders/Primary_Biliary_Cholangitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Primary_Biliary_Cholangitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Biliary_Cholangitis.html#dataset-geo-gse231432"}],"context_names":["Primary Biliary Cholangitis"],"disease_names":["Primary Biliary Cholangitis"],"disease_name":"Primary Biliary Cholangitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Primary_Biliary_Cholangitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Primary_Biliary_Cholangitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Primary_Biliary_Cholangitis.html#dataset-geo-gse231432"]},{"id":"dataset:geo:gse231664","accession":"geo:GSE231664","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE231664","title":"Nanostring of 3D hiPSC-derived neurons infected with rabies virus-wild type-thai strain (WT-TH) and rabies virus-challenge virus standard 11 (CVS-11) against uninfected controls at 8 and 24 hours post-infection","alternate_titles":[],"description":"This experiment is part of the project that primarily aims to utilize 3D hydrogel-based hiPSC-derived neuronal model to study rabies virus infection in the central nervous system. Having established the optimal 3D neuronal model, we then investigated the growth kinetics of two strains of rabies virus (TH and CVS-11) and comparatively analyzed the 2D and 3D culture models. We performed a gene expression analysis using NanoString to determine whether changes in gene expression could explain the differences in virus growth kinetics of two strains of rabies virus observed between the 2D and 3D neuronal culture models.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[36],"sample_count":36,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37692167"],"publication_contexts":[{"context_id":"disorder:Rabies","publication":"PMID:37692167"}],"publication":"PMID:37692167","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37692167","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Rabies (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Rabies","name":"Rabies","kind":"Disorder","source_path":"kb/disorders/Rabies.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rabies.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Rabies.html#dataset-geo-gse231664"}],"context_names":["Rabies"],"disease_names":["Rabies"],"disease_name":"Rabies","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Rabies.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rabies.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Rabies.html#dataset-geo-gse231664"]},{"id":"dataset:geo:gse231794","accession":"geo:GSE231794","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE231794","title":"Single-Cell Transcriptomics Reveals Peripheral Immune Responses in Non-Segmental Vitiligo","alternate_titles":[],"description":"Vitiligo is a common autoimmune depigmented dermatology due to the destruction of melanocytes. Much evidence suggests that vitiligo is associated with systemic immune activation. Previous studies have focused on immune cell infiltration in and around lesion areas, while few studies have investigated the cell types and function of circulating immune cells in peripheral blood. We collected peripheral blood from five patients with progressive non-segmental vitiligo (PV) and three healthy controls (HC).Single-cell RNA sequencing(scRNA-seq) is used to investigate the mechanisms of peripheral immune responses in vitiligo patients.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[8],"sample_count":8,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:38077333"],"publication_contexts":[{"context_id":"disorder:Vitiligo","publication":"PMID:38077333"}],"publication":"PMID:38077333","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38077333","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Vitiligo (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Vitiligo","name":"Vitiligo","kind":"Disorder","source_path":"kb/disorders/Vitiligo.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Vitiligo.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Vitiligo.html#dataset-geo-gse231794"}],"context_names":["Vitiligo"],"disease_names":["Vitiligo"],"disease_name":"Vitiligo","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Vitiligo.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Vitiligo.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Vitiligo.html#dataset-geo-gse231794"]},{"id":"dataset:geo:gse232100","accession":"geo:GSE232100","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE232100","title":"Circulating small RNA profiling of patients with alveolar and cystic echinococcosis","alternate_titles":[],"description":"Alveolar (AE) and cystic (CE) echinococcosis are two parasitic diseases caused by the tapeworms Echinococcus multilocularis and E. granulosus sensu lato (s. l.), respectively. Currently, AE and CE are mainly diagnosed by means of imaging techniques, supported by serology and clinical and epidemiological data. However, no viability markers that indicate parasite state during infection are available. Extracellular small RNAs (sRNAs) are short non-coding RNAs that can be secreted by cells through association with extracellular vesicles, proteins, or lipoproteins.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[27],"sample_count":27,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37237528"],"publication_contexts":[{"context_id":"disorder:Cystic_Echinococcosis","publication":"PMID:37237528"}],"publication":"PMID:37237528","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37237528","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Cystic echinococcosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Cystic_Echinococcosis","name":"Cystic echinococcosis","kind":"Disorder","source_path":"kb/disorders/Cystic_Echinococcosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cystic_Echinococcosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cystic_echinococcosis.html#dataset-geo-gse232100"}],"context_names":["Cystic echinococcosis"],"disease_names":["Cystic echinococcosis"],"disease_name":"Cystic echinococcosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cystic_Echinococcosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cystic_Echinococcosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cystic_echinococcosis.html#dataset-geo-gse232100"]},{"id":"dataset:geo:gse232641","accession":"geo:GSE232641","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE232641","title":"Differential Tropisms of Old and New World Hantaviruses Influence Virulence and Developing Host-Directed Antiviral Candidates","alternate_titles":[],"description":"Human primary lung endothelial cells, iPSC-derived cell types, and lung organoid models were used to define hantavirus tropism and infection-linked transcriptional responses.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40857262"],"publication_contexts":[{"context_id":"disorder:Hantavirus_Pulmonary_Syndrome","publication":"PMID:40857262"}],"publication":"PMID:40857262","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40857262","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":[],"contexts":[{"id":"disorder:Hantavirus_Pulmonary_Syndrome","name":"Hantavirus Pulmonary Syndrome","kind":"Disorder","source_path":"kb/disorders/Hantavirus_Pulmonary_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hantavirus_Pulmonary_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hantavirus_Pulmonary_Syndrome.html#dataset-geo-gse232641"}],"context_names":["Hantavirus Pulmonary Syndrome"],"disease_names":["Hantavirus Pulmonary Syndrome"],"disease_name":"Hantavirus Pulmonary Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hantavirus_Pulmonary_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hantavirus_Pulmonary_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hantavirus_Pulmonary_Syndrome.html#dataset-geo-gse232641"]},{"id":"dataset:geo:gse233180","accession":"geo:GSE233180","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE233180","title":"Thymic B lineage cell landscape in Myasthenia gravis","alternate_titles":[],"description":"Single-cell transcriptome and BCR data from immunotherapy-naive AChR-positive early-onset MG thymi. Twelve patients were recruited; one sample failed quality control, and the final reported atlas comprised 29,688 cells from 11 patients. Repository sample records and recruited patients are not interchangeable denominators.","alternate_descriptions":["Here, we provide a comprehensive and unbiased atlas of hematopoietic cell colonization in thymi derived from 12 immunotherapy-naïve patients with early-onset AChR-Ab+ MG (EOMG) using single-cell RNA sequencing (scRNA‑seq)."],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[24],"sample_count":24,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40117520"],"publication_contexts":[{"context_id":"disorder:Adult-Onset_Myasthenia_Gravis","publication":"PMID:40117520"},{"context_id":"disorder:Myasthenia_Gravis","publication":"PMID:40117520"}],"publication":"PMID:40117520","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40117520","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE233180","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE233180","reference_title":"Thymic B lineage cell landscape in Myasthenia gravis","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"Here, we provide a comprehensive and unbiased atlas of hematopoietic cell colonization in thymi derived from 12 immunotherapy-naïve patients with early-onset AChR-Ab+ MG (EOMG) using single-cell RNA sequencing (scRNA‑seq).","explanation":"Repository record describes the recruited dataset."},{"reference":"PMID:40117520","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40117520","reference_title":"Single-Cell Transcriptomics Identifies a Prominent Role for the MIF-CD74 Axis in Myasthenia Gravis Thymus.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"After enrichment for CD45+ hematopoietic cells, we profiled 29,688 individual cells and annotated 15 distinct populations","explanation":"Primary atlas after quality-control exclusions."}],"notes":["Accession verified with just verify-datasets; the per-record GEO cache is the verification artifact. Cell trajectories and MIF–CD74 communication are computational inferences, not lineage-tracing or signaling-intervention experiments.","Identified by GEO DataSets index search for Myasthenia Gravis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Adult-Onset_Myasthenia_Gravis","name":"Adult-Onset Myasthenia Gravis","kind":"Disorder","source_path":"kb/disorders/Adult-Onset_Myasthenia_Gravis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Adult-Onset_Myasthenia_Gravis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Adult-Onset_Myasthenia_Gravis.html#dataset-geo-gse233180"},{"id":"disorder:Myasthenia_Gravis","name":"Myasthenia Gravis","kind":"Disorder","source_path":"kb/disorders/Myasthenia_Gravis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myasthenia_Gravis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Myasthenia_Gravis.html#dataset-geo-gse233180"}],"context_names":["Adult-Onset Myasthenia Gravis","Myasthenia Gravis"],"disease_names":["Adult-Onset Myasthenia Gravis","Myasthenia Gravis"],"disease_name":"Adult-Onset Myasthenia Gravis","same_context_model_ids":["model:kb/disorders/Adult-Onset_Myasthenia_Gravis.yaml:AChR-Transfected HEK Antibody-Combination Assays","model:kb/disorders/Adult-Onset_Myasthenia_Gravis.yaml:Engineered MuSK Activation in 3T3 Fibroblasts","model:kb/disorders/Adult-Onset_Myasthenia_Gravis.yaml:Human iPSC-Derived Neuromuscular Coculture with MG Sera","model:kb/disorders/Adult-Onset_Myasthenia_Gravis.yaml:Patient MuSK IgG4 in Recombinant Binding and Myotube Assays"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Adult-Onset_Myasthenia_Gravis.yaml","kb/disorders/Myasthenia_Gravis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Adult-Onset_Myasthenia_Gravis.yaml","https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myasthenia_Gravis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Adult-Onset_Myasthenia_Gravis.html#dataset-geo-gse233180","https://dismech.monarchinitiative.org/pages/disorders/Myasthenia_Gravis.html#dataset-geo-gse233180"]},{"id":"dataset:geo:gse233280","accession":"geo:GSE233280","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE233280","title":"Single-cell RNA sequencing reveals dysregulated fibroblast subclusters in prurigo nodularis","alternate_titles":[],"description":"Prurigo nodularis (PN) is an intensely pruritic, inflammatory skin disease with a poorly understood pathogenesis. Thus, we performed single-cell transcriptomic profiling of 28,695 lesional and non-lesional PN cells. Lesional PN has increased dysregulated fibroblasts (FBs) and myofibroblasts. FBs in lesional PN were shifted towards a cancer-associated fibroblast (CAF)-like phenotype, with POSTN+WNT5A+ CAFs increased in PN, and similarly so in squamous cell carcinoma. A multi-center cohort study revealed an increased risk of SCC and CAF-associated malignancies (breast and colorectal) in PN patients.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:38246584"],"publication_contexts":[{"context_id":"disorder:Prurigo_Nodularis","publication":"PMID:38246584"}],"publication":"PMID:38246584","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38246584","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Prurigo Nodularis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Prurigo_Nodularis","name":"Prurigo Nodularis","kind":"Disorder","source_path":"kb/disorders/Prurigo_Nodularis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Prurigo_Nodularis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Prurigo_Nodularis.html#dataset-geo-gse233280"}],"context_names":["Prurigo Nodularis"],"disease_names":["Prurigo Nodularis"],"disease_name":"Prurigo Nodularis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Prurigo_Nodularis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Prurigo_Nodularis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Prurigo_Nodularis.html#dataset-geo-gse233280"]},{"id":"dataset:geo:gse23350","accession":"geo:GSE23350","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE23350","title":"Gene expression profile of patients affected by Metachromatic Leukodystrophy (MLD)","alternate_titles":[],"description":"The genome-wide analysis of T lympocytes from 24 MLD patients and a corresponding number of matched controls reveals a list of differentially expressed genes that can be used to build classifiers that correctly classify not only patients and controls with high sensitivity and specificity, but also MLD patients into early- and late-onset clinical classes.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[48],"sample_count":48,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:24242821"],"publication_contexts":[{"context_id":"disorder:Metachromatic_Leukodystrophy","publication":"PMID:24242821"}],"publication":"PMID:24242821","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/24242821","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Metachromatic Leukodystrophy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Metachromatic_Leukodystrophy","name":"Metachromatic Leukodystrophy","kind":"Disorder","source_path":"kb/disorders/Metachromatic_Leukodystrophy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Metachromatic_Leukodystrophy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Metachromatic_Leukodystrophy.html#dataset-geo-gse23350"}],"context_names":["Metachromatic Leukodystrophy"],"disease_names":["Metachromatic Leukodystrophy"],"disease_name":"Metachromatic Leukodystrophy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Metachromatic_Leukodystrophy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Metachromatic_Leukodystrophy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Metachromatic_Leukodystrophy.html#dataset-geo-gse23350"]},{"id":"dataset:geo:gse233973","accession":"geo:GSE233973","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE233973","title":"Comprehensive gene expression analysis using gastric mucosa with autoimmune gastritis","alternate_titles":[],"description":"In this study, we aimed to reveal whether gastric mucosa with AIG has a specific gene expression profile, involving in its histology and chronic inflammation. To approach this, we performed comprehensive analysis of gene expression using gastric mucosa with atuoimmune gastritis, that with H. pylori-associated gastritis and healthy mucosa without any inflammation. Potential mechanisms of the gene expression changes in gastric mucosa with AIG were also explored.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[36],"sample_count":36,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37962678"],"publication_contexts":[{"context_id":"disorder:Autoimmune_Gastritis","publication":"PMID:37962678"}],"publication":"PMID:37962678","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37962678","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Autoimmune Gastritis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Autoimmune_Gastritis","name":"Autoimmune Gastritis","kind":"Disorder","source_path":"kb/disorders/Autoimmune_Gastritis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autoimmune_Gastritis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autoimmune_Gastritis.html#dataset-geo-gse233973"}],"context_names":["Autoimmune Gastritis"],"disease_names":["Autoimmune Gastritis"],"disease_name":"Autoimmune Gastritis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Autoimmune_Gastritis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autoimmune_Gastritis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Autoimmune_Gastritis.html#dataset-geo-gse233973"]},{"id":"dataset:geo:gse234062","accession":"geo:GSE234062","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE234062","title":"Human Otic progenitor cell models of congenital hearing loss applied to to Zika virus and cytomegalovirus infections","alternate_titles":[],"description":"Congenital hearing loss is a common chronic condition affecting children in both developed and developing nations. In many cases, congenital hearing loss is ultimately attributed to viral infection, most often by cytomegalovirus (CMV), but also in Congenital Zika Syndrome (CZS). The mechanisms by which CMV and ZIKV virus cause these cranial developmental defects have not been elucidated. Inner ear development has been particularly difficult to study, given the inaccessibility and scarcity of the tissue in animal models or on human autopsy; however, it is now possible to culture stem-cell derived otic progenitor cells (OPCs).","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[36],"sample_count":36,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:38440980"],"publication_contexts":[{"context_id":"disorder:Congenital_Zika_Syndrome","publication":"PMID:38440980"}],"publication":"PMID:38440980","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38440980","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Congenital Zika Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Congenital_Zika_Syndrome","name":"Congenital Zika Syndrome","kind":"Disorder","source_path":"kb/disorders/Congenital_Zika_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Congenital_Zika_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Congenital_Zika_Syndrome.html#dataset-geo-gse234062"}],"context_names":["Congenital Zika Syndrome"],"disease_names":["Congenital Zika Syndrome"],"disease_name":"Congenital Zika Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Congenital_Zika_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Congenital_Zika_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Congenital_Zika_Syndrome.html#dataset-geo-gse234062"]},{"id":"dataset:geo:gse234085","accession":"geo:GSE234085","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE234085","title":"Differential expression of lncRNA in peripheral blood lymphocytes of Xinjiang Kazakh patients with essential hypertension","alternate_titles":[],"description":"Investigate long non-coding RNA (lncRNA) expression characteristics in the peripheral blood lymphocytes of Xinjiang Kazakh people with essential hypertension.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37396592"],"publication_contexts":[{"context_id":"disorder:Essential_Hypertension","publication":"PMID:37396592"}],"publication":"PMID:37396592","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37396592","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Essential Hypertension (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Essential_Hypertension","name":"Essential Hypertension","kind":"Disorder","source_path":"kb/disorders/Essential_Hypertension.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Essential_Hypertension.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Essential_Hypertension.html#dataset-geo-gse234085"}],"context_names":["Essential Hypertension"],"disease_names":["Essential Hypertension"],"disease_name":"Essential Hypertension","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Essential_Hypertension.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Essential_Hypertension.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Essential_Hypertension.html#dataset-geo-gse234085"]},{"id":"dataset:geo:gse234379","accession":"geo:GSE234379","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE234379","title":"DNA methylation profile in matched oral cavity squamous cell carcinoma and normal adjacent tissue samples","alternate_titles":[],"description":"Oral cavity squamous cell carcinoma (OSCC) is a complex and dynamic disease characterized by clinicopathological and molecular heterogeneity. Spatial and temporal heterogeneity of cell subpopulations has been associated with cancer progression and implicated in the prognosis and therapy response. Emerging evidence indicates that aberrant epigenetic profiles in OSCC may foster an immunosuppressive tumor microenvironment by modulating the expression of immune-related long non-coding RNAs (lncRNAs). DNA methylation analysis was performed in 46 matched OSCC and normal adjacent tissue samples using a genome-wide platform (Infinium HumanMethylation450 BeadChip).","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[92],"sample_count":92,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37742611"],"publication_contexts":[{"context_id":"disorder:Oral_Cavity_Squamous_Cell_Carcinoma","publication":"PMID:37742611"}],"publication":"PMID:37742611","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37742611","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Oral Cavity Squamous Cell Carcinoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Oral_Cavity_Squamous_Cell_Carcinoma","name":"Oral Cavity Squamous Cell Carcinoma","kind":"Disorder","source_path":"kb/disorders/Oral_Cavity_Squamous_Cell_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Oral_Cavity_Squamous_Cell_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Oral_Cavity_Squamous_Cell_Carcinoma.html#dataset-geo-gse234379"}],"context_names":["Oral Cavity Squamous Cell Carcinoma"],"disease_names":["Oral Cavity Squamous Cell Carcinoma"],"disease_name":"Oral Cavity Squamous Cell Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Oral_Cavity_Squamous_Cell_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Oral_Cavity_Squamous_Cell_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Oral_Cavity_Squamous_Cell_Carcinoma.html#dataset-geo-gse234379"]},{"id":"dataset:geo:gse235739","accession":"geo:GSE235739","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE235739","title":"ASPSCR1::TFE3 Drives Alveolar Soft Part Sarcoma by Inducing Targetable Transcriptional Programs","alternate_titles":[],"description":"This SuperSeries is composed of the SubSeries listed below. Alveolar soft part sarcoma (ASPS) is a rare mesenchymal malignancy driven by the ASPSCR1::TFE3 fusion. A better understanding of the mechanisms by which this oncogenic transcriptional regulator drives cancer growth is needed to help identify potential therapeutic targets. Here, we characterized the transcriptional and chromatin landscapes of ASPS tumors and preclinical models, identifying the essential role of ASPSCR1::TFE3 in tumor cell viability by regulating core transcriptional programs involved in cell proliferation, angiogenesis, and mitochondrial biology.","alternate_descriptions":[],"data_types":["MULTI_OMICS"],"data_type_labels":["Multi Omics"],"data_type_label":"Multi Omics","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[62],"sample_count":62,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:38657118"],"publication_contexts":[{"context_id":"disorder:Alveolar_Soft_Part_Sarcoma","publication":"PMID:38657118"}],"publication":"PMID:38657118","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38657118","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Alveolar Soft Part Sarcoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Alveolar_Soft_Part_Sarcoma","name":"Alveolar Soft Part Sarcoma","kind":"Disorder","source_path":"kb/disorders/Alveolar_Soft_Part_Sarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alveolar_Soft_Part_Sarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Alveolar_Soft_Part_Sarcoma.html#dataset-geo-gse235739"}],"context_names":["Alveolar Soft Part Sarcoma"],"disease_names":["Alveolar Soft Part Sarcoma"],"disease_name":"Alveolar Soft Part Sarcoma","same_context_model_ids":["model:kb/disorders/Alveolar_Soft_Part_Sarcoma.yaml:ASPSCR1-TFE3-Positive ASPS Tumor Cell Lines"],"candidate_model_ids":["model:kb/disorders/Alveolar_Soft_Part_Sarcoma.yaml:ASPSCR1-TFE3-Positive ASPS Tumor Cell Lines"],"association_basis":"Same publication as a NAM (candidate)","nam_disease_context":"Same publication as a NAM (candidate)","source_paths":["kb/disorders/Alveolar_Soft_Part_Sarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alveolar_Soft_Part_Sarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Alveolar_Soft_Part_Sarcoma.html#dataset-geo-gse235739"]},{"id":"dataset:geo:gse236097","accession":"geo:GSE236097","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE236097","title":"Unravelling Stargardt Disease (STGD1): Modelling Genotype-Phenotype Correlations and Unresolved Genetic Variants in iPSC-Derived Retinal Organoids","alternate_titles":[],"description":"Human retinal organoid transcriptomic dataset from unresolved and genetically confirmed STGD1 cases used to model genotype-phenotype relationships, stress pathways, and retina-specific splicing defects in ABCA4-associated disease.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0000966","label":"retina","display_label":"retinal organoid","url":"http://purl.obolibrary.org/obo/UBERON_0000966"}],"sample_type_labels":["retina"],"sample_counts":[4],"sample_count":4,"conditions":["Stargardt disease","late-onset STGD1","unaffected control"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39971915"],"publication_contexts":[{"context_id":"disorder:Stargardt_Disease","publication":"PMID:39971915"}],"publication":"PMID:39971915","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39971915","publication_status":"Publication recorded","findings":[{"statement":"Patient-derived retinal organoids recapitulate genotype-dependent lamination defects, photoreceptor retention, and retina-specific splicing abnormalities in STGD1.","evidence":[{"reference":"PMID:39971915","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39971915","reference_title":"Unravelling genotype-phenotype correlations in Stargardt disease using patient-derived retinal organoids.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Collectively, these results highlight the suitability of retinal organoids in STGD1 modelling.","explanation":"This supports the dataset as a disease-relevant human organoid resource for mechanistic and genotype-phenotype analysis."},{"reference":"PMID:39971915","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39971915","reference_title":"Unravelling genotype-phenotype correlations in Stargardt disease using patient-derived retinal organoids.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Their ability to display genotype-phenotype correlations enhances their utility as a platform for therapeutic development.","explanation":"This supports the value of the dataset for stratifying disease severity and therapeutic-response hypotheses."}]}],"findings_text":["Patient-derived retinal organoids recapitulate genotype-dependent lamination defects, photoreceptor retention, and retina-specific splicing abnormalities in STGD1."],"evidence":[{"reference":"PMID:39971915","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39971915","reference_title":"Unravelling genotype-phenotype correlations in Stargardt disease using patient-derived retinal organoids.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Collectively, these results highlight the suitability of retinal organoids in STGD1 modelling.","explanation":"This supports inclusion of the GEO series as a disease-relevant STGD1 research dataset."},{"reference":"PMID:39971915","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39971915","reference_title":"Unravelling genotype-phenotype correlations in Stargardt disease using patient-derived retinal organoids.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Their ability to display genotype-phenotype correlations enhances their utility as a platform for therapeutic development.","explanation":"This supports the value of the dataset for stratifying disease severity and therapeutic-response hypotheses."}],"notes":[],"contexts":[{"id":"disorder:Stargardt_Disease","name":"Stargardt Disease","kind":"Disorder","source_path":"kb/disorders/Stargardt_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Stargardt_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Stargardt_Disease.html#dataset-geo-gse236097"}],"context_names":["Stargardt Disease"],"disease_names":["Stargardt Disease"],"disease_name":"Stargardt Disease","same_context_model_ids":["model:kb/disorders/Stargardt_Disease.yaml:Patient-derived retinal organoid model","model:kb/disorders/Stargardt_Disease.yaml:STGD1 iPSC-derived RPE disease-in-a-dish model"],"candidate_model_ids":["model:kb/disorders/Stargardt_Disease.yaml:Patient-derived retinal organoid model"],"association_basis":"Same publication as a NAM (candidate)","nam_disease_context":"Same publication as a NAM (candidate)","source_paths":["kb/disorders/Stargardt_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Stargardt_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Stargardt_Disease.html#dataset-geo-gse236097"]},{"id":"dataset:geo:gse236191","accession":"geo:GSE236191","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE236191","title":"Specific biological processes associated with T2D-induced left ventricular dysfunction in patients with aortic stenosis pressure overload","alternate_titles":[],"description":"Background: Type 2 diabetes (T2D) is increasingly prevalent and increases the risk of developing heart failure. T2D is frequently associated with left ventricular (LV) pressure overload, such as encountered in hypertension and aortic stenosis (AS), and few studies suggested an aggravating effect of T2D. We aimed to explore if the deleterious impact of T2D on LV remodeling and function in patients with AS is associated with specific biological processes.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[47],"sample_count":47,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Heart Failure (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Heart_Failure","name":"Heart Failure","kind":"Disorder","source_path":"kb/disorders/Heart_Failure.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Heart_Failure.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Heart_Failure.html#dataset-geo-gse236191"}],"context_names":["Heart Failure"],"disease_names":["Heart Failure"],"disease_name":"Heart Failure","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Heart_Failure.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Heart_Failure.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Heart_Failure.html#dataset-geo-gse236191"]},{"id":"dataset:geo:gse236382","accession":"geo:GSE236382","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE236382","title":"Single-cell transcriptome characterization of the livers from patients with alcoholic liver disease","alternate_titles":[],"description":"Human liver single-cell RNA-sequencing dataset used to characterize hepatic immune-cell landscapes in ALD. The five ALD cases provide associative cellular context and should not be interpreted as causal or population-representative.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0002107","label":"liver","display_label":"liver tissue","url":"http://purl.obolibrary.org/obo/UBERON_0002107"}],"sample_type_labels":["liver"],"sample_counts":[5],"sample_count":5,"conditions":["alcohol-associated liver disease"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39349248"],"publication_contexts":[{"context_id":"disorder:Alcoholic_Liver_Disease","publication":"PMID:39349248"}],"publication":"PMID:39349248","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39349248","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:39349248","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39349248","reference_title":"Single-cell Profiling of Intrahepatic Immune Cells Reveals an Expansion of Tissue-resident Cytotoxic CD4(+) T Lymphocyte Subset Associated With Pathogenesis of Alcoholic-associated Liver Diseases.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"We utilized single-cell RNA sequencing to analyze liver samples from healthy subjects and patients with MASLD and ALD, focusing on the immune cell landscapes within the liver.","explanation":"The publication confirms single-cell analysis of human liver samples including ALD."},{"reference":"GEO:GSE236382","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE236382","reference_title":"Single-cell transcriptome characterization of the livers from patients with alcoholic liver disease","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"This study utilized single-cell data from liver samples of 5 ALD human cases.","explanation":"The GEO record directly supports the ALD sample count."}],"notes":["Dataset record: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE236382"],"contexts":[{"id":"disorder:Alcoholic_Liver_Disease","name":"Alcohol-Associated Liver Disease","kind":"Disorder","source_path":"kb/disorders/Alcoholic_Liver_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alcoholic_Liver_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Alcohol-Associated_Liver_Disease.html#dataset-geo-gse236382"}],"context_names":["Alcohol-Associated Liver Disease"],"disease_names":["Alcohol-Associated Liver Disease"],"disease_name":"Alcohol-Associated Liver Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Alcoholic_Liver_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alcoholic_Liver_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Alcohol-Associated_Liver_Disease.html#dataset-geo-gse236382"]},{"id":"dataset:geo:gse236595","accession":"geo:GSE236595","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE236595","title":"An antisense oligonucleotide-based strategy to ameliorate cognitive dysfunction in the 22q11.2 Deletion Syndrome [RNA-seq]","alternate_titles":[],"description":"Adults and children with the 22q11.2 Deletion Syndrome demonstrate cognitive, social and emotional impairments and high risk for schizophrenia. Work in mouse model of the 22q11.2 deletion provided compelling evidence for abnormal expression and processing of microRNAs. A major transcriptional effect of the microRNA dysregulation is up-regulation of Emc10, a component of the ER membrane complex, which promotes membrane insertion of a subset of polytopic and tail-anchored membrane proteins. We previously uncovered a key contribution of EMC10 in mediating the behavioral phenotypes observed in 22q11.2 deletion mouse models.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40420562"],"publication_contexts":[{"context_id":"disorder:22q11.2_Deletion_Syndrome","publication":"PMID:40420562"}],"publication":"PMID:40420562","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40420562","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for 22q11.2 Deletion Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:22q11.2_Deletion_Syndrome","name":"22q11.2 Deletion Syndrome","kind":"Disorder","source_path":"kb/disorders/22q11.2_Deletion_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/22q11.2_Deletion_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/22q11.2_Deletion_Syndrome.html#dataset-geo-gse236595"}],"context_names":["22q11.2 Deletion Syndrome"],"disease_names":["22q11.2 Deletion Syndrome"],"disease_name":"22q11.2 Deletion Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/22q11.2_Deletion_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/22q11.2_Deletion_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/22q11.2_Deletion_Syndrome.html#dataset-geo-gse236595"]},{"id":"dataset:geo:gse237021","accession":"geo:GSE237021","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE237021","title":"KAT6A mutations in Arboleda-Tham syndrome affect regulation and expression of HOXC genes [ChIP-seq]","alternate_titles":[],"description":"Arboleda-Tham Syndrome (ARTHS) is a rare genetic disorder caused by heterozygous, de novo truncating mutations in the gene KAT6A (Lysine(K) acetyltransferase 6A). ARTHS is clinically heterogeneous but characterized by several common features including intellectual disability, developmental and speech delay, hypotonia, congenital heart defects and gastrointestinal problems. KAT6A mRNA is highly expressed throughout early development and the levels of expression are lower levels in differentiated tissues, suggesting a key role maintenance of the stem cell characteristics.","alternate_descriptions":[],"data_types":["CHIP_SEQ"],"data_type_labels":["Chromatin immunoprecipitation sequencing"],"data_type_label":"Chromatin immunoprecipitation sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[14],"sample_count":14,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Arboleda-Tham Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Arboleda-Tham_Syndrome","name":"Arboleda-Tham Syndrome","kind":"Disorder","source_path":"kb/disorders/Arboleda-Tham_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Arboleda-Tham_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Arboleda-Tham_Syndrome.html#dataset-geo-gse237021"}],"context_names":["Arboleda-Tham Syndrome"],"disease_names":["Arboleda-Tham Syndrome"],"disease_name":"Arboleda-Tham Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Arboleda-Tham_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Arboleda-Tham_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Arboleda-Tham_Syndrome.html#dataset-geo-gse237021"]},{"id":"dataset:geo:gse237022","accession":"geo:GSE237022","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE237022","title":"KAT6A mutations in Arboleda-Tham syndrome affect regulation and expression of HOXC genes [RNA-seq]","alternate_titles":[],"description":"Arboleda-Tham Syndrome (ARTHS) is a rare genetic disorder caused by heterozygous, de novo truncating mutations in the gene KAT6A (Lysine(K) acetyltransferase 6A). ARTHS is clinically heterogeneous but characterized by several common features including intellectual disability, developmental and speech delay, hypotonia, congenital heart defects and gastrointestinal problems. 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In addition, ortholog mapping allowed to obtain highly concordant biological 1:1 human ortholog genes for the detection of gene-disease associations (GDAs) and disease enriched pathways.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:7955","label":"Danio rerio","display_label":"zebrafish","url":"http://purl.obolibrary.org/obo/NCBITaxon_7955"}],"organism_labels":["Danio rerio"],"organism_label":"Danio rerio","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37922649"],"publication_contexts":[{"context_id":"disorder:Alpha-gal_Syndrome","publication":"PMID:37922649"}],"publication":"PMID:37922649","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37922649","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Alpha-gal Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. 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However, a direct assessment of IL-17 signaling in PSC cholangiocytes is lacking. Cholangiocytes obtained from PSC and non-PSC patients by endoscopic retrograde cholangiography (ERC) were cultured as extrahepatic cholangiocyte organoids (ECO). The ECO were treated with vehicle or IL-17A and assessed by NanoString analysis, single cell RNA sequencing (scRNA-seq), and whole genome sequencing (WGS). The secretome was assessed by Olink analysis.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[16],"sample_count":16,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Primary Sclerosing Cholangitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. 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matched WT controls.","explanation":"This supports the dataset as a comparative transcriptomic resource across mechanistically distinct Stargardt mouse models."},{"reference":"PMID:38064509","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38064509","reference_title":"Distinct mouse models of Stargardt disease display differences in pharmacological targeting of ceramides and inflammatory responses.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"We found different degrees of responsiveness to maraviroc, a known immunomodulatory CCR5 antagonist, and to the ceramide-lowering agent AdipoRon, an agonist of the ADIPOR1 and ADIPOR2 receptors.","explanation":"This supports the dataset's value for studying treatment-response heterogeneity across Stargardt models."}]}],"findings_text":["Distinct Abca4 mutant mouse retinas show different transcriptional responses and pharmacologic sensitivities, making the dataset useful for comparative mechanism and intervention studies."],"evidence":[{"reference":"PMID:38064509","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38064509","reference_title":"Distinct mouse models of Stargardt disease display differences in pharmacological targeting of ceramides and inflammatory responses.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"Using a combination of molecular techniques, we studied Abca4 knockout (simulating human noncoding disease variants) and Abca4 knock-in mice (simulating human misfolded, catalytically inactive protein variants), which serve as models for Stargardt-1 disease.","explanation":"This supports inclusion of the GEO series as a comparative transcriptomic dataset built from established Stargardt mouse models."},{"reference":"PMID:38064509","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38064509","reference_title":"Distinct mouse models of Stargardt disease display differences in pharmacological targeting of ceramides and inflammatory responses.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"The two strains also display different degrees of transcriptional deviation from matched WT controls.","explanation":"This supports the dataset as a comparative transcriptomic resource across mechanistically distinct Stargardt mouse models."},{"reference":"PMID:38064509","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38064509","reference_title":"Distinct mouse models of Stargardt disease display differences in pharmacological targeting of ceramides and inflammatory responses.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"We found different degrees of responsiveness to maraviroc, a known immunomodulatory CCR5 antagonist, and to the ceramide-lowering agent AdipoRon, an agonist of the ADIPOR1 and ADIPOR2 receptors.","explanation":"This supports the dataset's value for studying treatment-response heterogeneity across Stargardt 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NAM","source_paths":["kb/disorders/Stargardt_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Stargardt_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Stargardt_Disease.html#dataset-geo-gse239347"]},{"id":"dataset:geo:gse239531","accession":"geo:GSE239531","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE239531","title":"Multimodal profiling of chordoma immunity reveals distinct immune contextures","alternate_titles":[],"description":"Chordomas are cancers from the axial skeleton presenting immunological hallmarks of unknown significance. In recent years, some clinical trials demonstrated that chordomas can respond to immunotherapy. We present a comprehensive characterisation of immunological features of 76 chordomas through application of a multimodal approach comprising transcriptional profiling, multidimensional immunophenotyping and TCR profiling. Chordomas generally presented an immune “hot” microenvironment in comparison to other sarcomas, as indicated by the immunologic constant of rejection transcriptional signature. We identified two distinct groups of chordomas based on T cell infiltration.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[20],"sample_count":20,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:38272563"],"publication_contexts":[{"context_id":"disorder:Chordoma","publication":"PMID:38272563"}],"publication":"PMID:38272563","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38272563","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Chordoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Chordoma","name":"Chordoma","kind":"Disorder","source_path":"kb/disorders/Chordoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chordoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chordoma.html#dataset-geo-gse239531"}],"context_names":["Chordoma"],"disease_names":["Chordoma"],"disease_name":"Chordoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chordoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chordoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chordoma.html#dataset-geo-gse239531"]},{"id":"dataset:geo:gse239715","accession":"geo:GSE239715","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE239715","title":"Epigenome analysis of schwannomas arising as part of segmental schwannomatosis due to somatic mosaic SOX10 indel mutations","alternate_titles":[],"description":"Genome-wide DNA methylation profiling of 6 schwannomas arising as part of segmental schwannomatosis due to somatic mosaic SOX10 indel mutations. The Illumina Infinium EPIC 850k Human DNA Methylation Beadchip was used to obtain DNA methylation profiles across approximately 850,000 CpG sites of genomic DNA extracted from formalin-fixed, paraffin-embedded tumor tissue of 6 schwannomas.","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37821623"],"publication_contexts":[{"context_id":"disorder:Schwannomatosis","publication":"PMID:37821623"}],"publication":"PMID:37821623","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37821623","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Schwannomatosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Schwannomatosis","name":"Schwannomatosis","kind":"Disorder","source_path":"kb/disorders/Schwannomatosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Schwannomatosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Schwannomatosis.html#dataset-geo-gse239715"}],"context_names":["Schwannomatosis"],"disease_names":["Schwannomatosis"],"disease_name":"Schwannomatosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Schwannomatosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Schwannomatosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Schwannomatosis.html#dataset-geo-gse239715"]},{"id":"dataset:geo:gse239758","accession":"geo:GSE239758","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE239758","title":"The mRNA-lncRNA-circRNA network profiling of Turner syndrome patient-derived induced pluripotent stem cells and their derived cardiomyocytes","alternate_titles":[],"description":"Coding and non-coding RNA microarray profiles from three 45,X Turner and three healthy-donor iPSC lines and their matched day-14 cardiomyocyte derivatives.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"CL:0000746","label":"cardiac muscle cell","display_label":"cardiomyocyte","url":"http://purl.obolibrary.org/obo/CL_0000746"}],"sample_type_labels":["cardiac muscle cell"],"sample_counts":[12],"sample_count":12,"conditions":["45,X Turner syndrome-derived iPSCs and cardiomyocytes","46,XX healthy-donor-derived iPSCs and cardiomyocytes"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["High-density mRNA, lncRNA, and circRNA microarrays"],"platform":"High-density mRNA, lncRNA, and circRNA microarrays","publications":["PMID:38124119"],"publication_contexts":[{"context_id":"disorder:Turner_Syndrome","publication":"PMID:38124119"}],"publication":"PMID:38124119","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38124119","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:38124119","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38124119","reference_title":"Competing endogenous RNA network analysis of Turner syndrome patient-specific iPSC-derived cardiomyocytes reveals dysregulation of autosomal heart development genes by altered dosages of X-inactivation escaping non-coding RNAs.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The microarray data were deposited in the Gene Expression Omnibus (GEO) database under the accession no. GSE239758.","explanation":"Direct accession statement from the primary publication."}],"notes":["Direct disease-model dataset discovered with `just discover-datasets`; accession, organism, publication, data type, and 12-sample count verified against NCBI GEO metadata on 2026-08-16."],"contexts":[{"id":"disorder:Turner_Syndrome","name":"Turner Syndrome","kind":"Disorder","source_path":"kb/disorders/Turner_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Turner_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Turner_Syndrome.html#dataset-geo-gse239758"}],"context_names":["Turner Syndrome"],"disease_names":["Turner Syndrome"],"disease_name":"Turner Syndrome","same_context_model_ids":["model:kb/disorders/Turner_Syndrome.yaml:45,X patient-derived iPSC cardiomyocytes","model:kb/disorders/Turner_Syndrome.yaml:45,X patient-derived iPSC granulosa-like cells"],"candidate_model_ids":["model:kb/disorders/Turner_Syndrome.yaml:45,X patient-derived iPSC cardiomyocytes"],"association_basis":"Same publication as a NAM (candidate)","nam_disease_context":"Same publication as a NAM (candidate)","source_paths":["kb/disorders/Turner_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Turner_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Turner_Syndrome.html#dataset-geo-gse239758"]},{"id":"dataset:geo:gse239914","accession":"geo:GSE239914","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE239914","title":"Deciphering disease signatures and molecular targets in vascular Ehlers-Danlos syndrome through transcriptome sequencing of a large cohort of patients’ dermal fibroblasts","alternate_titles":[],"description":"Vascular Ehlers-Danlos syndrome (vEDS) is a severe connective tissue disorder caused by dominant mutations in the COL3A1 gene, which encodes type III collagen (COLLIII). COLLIII is primarily found in blood vessels and hollow organs, and its deficiency causes fragile soft connective tissues, with life-threatening arterial and organ ruptures. There are currently no targeted therapies available. Although disease results from COLLIII misfolding caused by triple helix structure disruption, the underlying pathomechanisms are largely unknown.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[108],"sample_count":108,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37827202"],"publication_contexts":[{"context_id":"disorder:Ehlers-Danlos_Syndrome","publication":"PMID:37827202"}],"publication":"PMID:37827202","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37827202","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Ehlers-Danlos Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Ehlers-Danlos_Syndrome","name":"Ehlers-Danlos Syndrome","kind":"Disorder","source_path":"kb/disorders/Ehlers-Danlos_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ehlers-Danlos_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Ehlers-Danlos_Syndrome.html#dataset-geo-gse239914"}],"context_names":["Ehlers-Danlos Syndrome"],"disease_names":["Ehlers-Danlos Syndrome"],"disease_name":"Ehlers-Danlos Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Ehlers-Danlos_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ehlers-Danlos_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Ehlers-Danlos_Syndrome.html#dataset-geo-gse239914"]},{"id":"dataset:geo:gse2401","accession":"geo:GSE2401","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE2401","title":"Gene expression in Hypotension","alternate_titles":[],"description":"Rat kidney in normo- and hypotensive animals. Keywords: parallel sample","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:10116","label":"Rattus norvegicus","display_label":"rat","url":"http://purl.obolibrary.org/obo/NCBITaxon_10116"}],"organism_labels":["Rattus norvegicus"],"organism_label":"Rattus norvegicus","sample_types":[],"sample_type_labels":[],"sample_counts":[9],"sample_count":9,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:15942020"],"publication_contexts":[{"context_id":"disorder:Acute_Hypotension","publication":"PMID:15942020"}],"publication":"PMID:15942020","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/15942020","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Acute Hypotension (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Acute_Hypotension","name":"Acute Hypotension","kind":"Disorder","source_path":"kb/disorders/Acute_Hypotension.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Acute_Hypotension.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Acute_Hypotension.html#dataset-geo-gse2401"}],"context_names":["Acute Hypotension"],"disease_names":["Acute Hypotension"],"disease_name":"Acute Hypotension","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Acute_Hypotension.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Acute_Hypotension.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Acute_Hypotension.html#dataset-geo-gse2401"]},{"id":"dataset:geo:gse240260","accession":"geo:GSE240260","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE240260","title":"Target gene regulatory network of miR-497 in angiosarcoma","alternate_titles":[],"description":"Angiosarcoma (AS) is a vascular sarcoma that is highly aggressive and metastatic. Due to its rarity, treatment options for patients are limited, therefore more research is needed to identify possible therapeutic vulnerabilities. We previously found that endothelial deletion of Dicer1 drives AS development in mice. Given the role of DICER1 in canonical microRNA (miRNA) biogenesis, this suggests that miRNA loss may be important in AS development. After testing miRNAs previously suggested to have a tumor-suppressive role in AS, microRNA-497-5p (miR-497) suppressed cell viability most significantly.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37808715"],"publication_contexts":[{"context_id":"disorder:Angiosarcoma","publication":"PMID:37808715"}],"publication":"PMID:37808715","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37808715","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Angiosarcoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Angiosarcoma","name":"Angiosarcoma","kind":"Disorder","source_path":"kb/disorders/Angiosarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Angiosarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Angiosarcoma.html#dataset-geo-gse240260"}],"context_names":["Angiosarcoma"],"disease_names":["Angiosarcoma"],"disease_name":"Angiosarcoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Angiosarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Angiosarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Angiosarcoma.html#dataset-geo-gse240260"]},{"id":"dataset:geo:gse240611","accession":"geo:GSE240611","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE240611","title":"Prenatal phenotypes and pregnancy outcomes of fetuses with recurrent 1q21.1 microdeletions and microduplications","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[26],"sample_count":26,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37692779"],"publication_contexts":[{"context_id":"disorder:Thrombocytopenia-Absent_Radius_Syndrome","publication":"PMID:37692779"}],"publication":"PMID:37692779","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37692779","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Prenatal cohort of recurrent 1q21.1 copy-number changes, which names TAR among the associated phenotypes. Relevant to the null allele rather than to TAR specifically, since the cohort is ascertained on the CNV and includes duplications and unaffected outcomes; use for deletion-level context, not as a TAR case series."],"contexts":[{"id":"disorder:Thrombocytopenia-Absent_Radius_Syndrome","name":"Thrombocytopenia-Absent Radius Syndrome","kind":"Disorder","source_path":"kb/disorders/Thrombocytopenia-Absent_Radius_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Thrombocytopenia-Absent_Radius_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Thrombocytopenia-Absent_Radius_Syndrome.html#dataset-geo-gse240611"}],"context_names":["Thrombocytopenia-Absent Radius Syndrome"],"disease_names":["Thrombocytopenia-Absent Radius Syndrome"],"disease_name":"Thrombocytopenia-Absent Radius Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Thrombocytopenia-Absent_Radius_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Thrombocytopenia-Absent_Radius_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Thrombocytopenia-Absent_Radius_Syndrome.html#dataset-geo-gse240611"]},{"id":"dataset:geo:gse240851","accession":"geo:GSE240851","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE240851","title":"The Transcriptomic Profiling of Blood CD4 and CD8 T-cells in Narcolepsy Type I","alternate_titles":[],"description":"Background Narcolepsy Type I (NT1) is a rare, life-long sleep disorder arising as a consequence of the extensive destruction of orexin-producing hypothalamic neurons. The mechanisms involved in the destruction of orexin neurons are not yet elucidated but the association of narcolepsy with environmental triggers and genetic susceptibility (strong association with the HLA, TCRs and other immunologically-relevant loci) implicates an immuno-pathological process.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[260],"sample_count":260,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:38077397"],"publication_contexts":[{"context_id":"disorder:Narcolepsy","publication":"PMID:38077397"}],"publication":"PMID:38077397","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38077397","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Narcolepsy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Narcolepsy","name":"Narcolepsy","kind":"Disorder","source_path":"kb/disorders/Narcolepsy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Narcolepsy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Narcolepsy.html#dataset-geo-gse240851"}],"context_names":["Narcolepsy"],"disease_names":["Narcolepsy"],"disease_name":"Narcolepsy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Narcolepsy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Narcolepsy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Narcolepsy.html#dataset-geo-gse240851"]},{"id":"dataset:geo:gse241258","accession":"geo:GSE241258","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE241258","title":"Regulatory role of Gnao1 in neuronal differentitation","alternate_titles":[],"description":"RNA sequencing of Neuro2a cells after siRNA-mediated silencing of Gnao1, reported by its authors as a route into the molecular mechanisms underlying GNAO1-associated developmental and epileptic encephalopathy. Note this is a knockdown of the wild-type gene in a mouse neuroblastoma line, so it models Gao depletion rather than the dominant-negative missense alleles that cause most human disease.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"house mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:4389","label":"GNAO1","display_label":"GNAO1","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/4389"}],"genes":["GNAO1"],"platforms":[],"platform":null,"publications":["PMID:39048611"],"publication_contexts":[{"context_id":"disorder:GNAO1-Related_Developmental_and_Epileptic_Encephalopathy","publication":"PMID:39048611"}],"publication":"PMID:39048611","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39048611","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Found by a targeted GEO DataSets title search for GNAO1; accession and metadata verified against NCBI E-utilities on 2026-08-27. Title (including its typo), sample count, and organism are GEO's own values. Cell-line data from a mouse neuroblastoma line - the gene descriptor is the human HGNC record for the disease gene."],"contexts":[{"id":"disorder:GNAO1-Related_Developmental_and_Epileptic_Encephalopathy","name":"GNAO1-Related Developmental and Epileptic Encephalopathy","kind":"Disorder","source_path":"kb/disorders/GNAO1-Related_Developmental_and_Epileptic_Encephalopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/GNAO1-Related_Developmental_and_Epileptic_Encephalopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/GNAO1-Related_Developmental_and_Epileptic_Encephalopathy.html#dataset-geo-gse241258"}],"context_names":["GNAO1-Related Developmental and Epileptic Encephalopathy"],"disease_names":["GNAO1-Related Developmental and Epileptic Encephalopathy"],"disease_name":"GNAO1-Related Developmental and Epileptic Encephalopathy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/GNAO1-Related_Developmental_and_Epileptic_Encephalopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/GNAO1-Related_Developmental_and_Epileptic_Encephalopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/GNAO1-Related_Developmental_and_Epileptic_Encephalopathy.html#dataset-geo-gse241258"]},{"id":"dataset:geo:gse241671","accession":"geo:GSE241671","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE241671","title":"Differential effects of lithium on metabolic dysfunction in astrocytes derived from bipolar disorder patients","alternate_titles":[],"description":"Metabolic alterations have been observed in the brains of patients with bipolar disorder (BD), a neuropsychiatric disorder characterized by biphasic mood episodes of mania and depression. However, the specific contributions of glial cells to these metabolic changes in BD patients remain largely unknown and have not been extensively studied. Here, we investigate the metabolic characteristics of induced astrocytes (iAstrocytes) derived from induced pluripotent stem cells of BD patients and their responses to lithium treatment. The gene expression profiles of iAstrocytes from BD patients (BD iAstrocytes) indicate dysregulation of metabolic processes in BD iAstrocytes.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[30],"sample_count":30,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40847005"],"publication_contexts":[{"context_id":"disorder:Bipolar_Disorder","publication":"PMID:40847005"}],"publication":"PMID:40847005","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40847005","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Bipolar Disorder (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Bipolar_Disorder","name":"Bipolar Disorder","kind":"Disorder","source_path":"kb/disorders/Bipolar_Disorder.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bipolar_Disorder.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Bipolar_Disorder.html#dataset-geo-gse241671"}],"context_names":["Bipolar Disorder"],"disease_names":["Bipolar Disorder"],"disease_name":"Bipolar Disorder","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Bipolar_Disorder.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bipolar_Disorder.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Bipolar_Disorder.html#dataset-geo-gse241671"]},{"id":"dataset:geo:gse242159","accession":"geo:GSE242159","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE242159","title":"Effect of 8-weeks of chronic jet lag lighting (CJL) on gene expression in the livers of Eu-MYC mice","alternate_titles":[],"description":"Background: Disruption of natural diurnal light cycles, such as that experienced by shift workers, is linked to enhanced cancer incidence. Several mouse models of cancer have been shown to develop more severe disease when exposed to irregular light/dark cycles, further supporting the connection between circadian disruption and increased cancer risk. Cryptochrome 2 (CRY2), a repressive component of the molecular circadian clock, facilitates the turnover of the oncoprotein c-MYC, one mechanism that may link the molecular clock to tumorigenesis.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[26],"sample_count":26,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Jet Lag (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Jet_Lag","name":"Jet Lag","kind":"Disorder","source_path":"kb/disorders/Jet_Lag.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Jet_Lag.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Jet_Lag.html#dataset-geo-gse242159"}],"context_names":["Jet Lag"],"disease_names":["Jet Lag"],"disease_name":"Jet Lag","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Jet_Lag.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Jet_Lag.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Jet_Lag.html#dataset-geo-gse242159"]},{"id":"dataset:geo:gse242232","accession":"geo:GSE242232","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE242232","title":"Autoantigen-specific CD4+ T cells acquire an exhausted phenotype and persist in human antigen-specific autoimmune diseases","alternate_titles":[],"description":"Pro-inflammatory autoantigen-specific CD4+ T helper (auto-Th) cells are central orchestrators of autoimmune diseases (AIDs). We aimed to characterize these cells in human AIDs with defined autoantigens by combining human leukocyte antigen (HLA)-tetramer-based and activation-based multidimensional ex vivo analyses. In aquaporin4-antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) patients, auto-Th cells expressed CD154, but proliferative capacity and pro-inflammatory cytokines were strongly reduced. Instead, exhaustion-associated co-inhibitory receptors were expressed together with FOXP3, the canonical regulatory T cell (Treg) transcription factor.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[928],"sample_count":928,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39226901"],"publication_contexts":[{"context_id":"disorder:Neuromyelitis_Optica","publication":"PMID:39226901"},{"context_id":"disorder:Neuromyelitis_Optica_Spectrum_Disorder","publication":"PMID:39226901"}],"publication":"PMID:39226901","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39226901","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Neuromyelitis Optica (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.","Identified by GEO DataSets index search for Neuromyelitis Optica Spectrum Disorder (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Neuromyelitis_Optica","name":"Neuromyelitis Optica","kind":"Disorder","source_path":"kb/disorders/Neuromyelitis_Optica.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Neuromyelitis_Optica.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Neuromyelitis_Optica.html#dataset-geo-gse242232"},{"id":"disorder:Neuromyelitis_Optica_Spectrum_Disorder","name":"Neuromyelitis Optica Spectrum Disorder","kind":"Disorder","source_path":"kb/disorders/Neuromyelitis_Optica_Spectrum_Disorder.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Neuromyelitis_Optica_Spectrum_Disorder.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Neuromyelitis_Optica_Spectrum_Disorder.html#dataset-geo-gse242232"}],"context_names":["Neuromyelitis Optica","Neuromyelitis Optica Spectrum Disorder"],"disease_names":["Neuromyelitis Optica","Neuromyelitis Optica Spectrum Disorder"],"disease_name":"Neuromyelitis Optica","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Neuromyelitis_Optica.yaml","kb/disorders/Neuromyelitis_Optica_Spectrum_Disorder.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Neuromyelitis_Optica.yaml","https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Neuromyelitis_Optica_Spectrum_Disorder.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Neuromyelitis_Optica.html#dataset-geo-gse242232","https://dismech.monarchinitiative.org/pages/disorders/Neuromyelitis_Optica_Spectrum_Disorder.html#dataset-geo-gse242232"]},{"id":"dataset:geo:gse242389","accession":"geo:GSE242389","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE242389","title":"Human birth tissue products as a regenerative medicine for post-surgical pain through multi-modal action","alternate_titles":[],"description":"Post-surgical pain causes significant suffering. Extracts of the human amniotic membrane (AM) may be novel regenerative matrices, but little is known about their use in pain treatment. Locally applying FLO (particulates of AM) in mice acutely attenuated post-surgical pain hypersensitivity and inhibited its transition to a prolonged state after plantar-incision. Mechanistically, this was achieved through direct nociceptive neuronal inhibition via CD44-dependent mechanisms and indirect anti-pain effect by attenuating immune cell recruitment and promoting wound healing.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39594635"],"publication_contexts":[{"context_id":"disorder:Acute_Post-Surgical_Pain","publication":"PMID:39594635"}],"publication":"PMID:39594635","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39594635","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Acute Post-Surgical Pain (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Acute_Post-Surgical_Pain","name":"Acute Post-Surgical Pain","kind":"Disorder","source_path":"kb/disorders/Acute_Post-Surgical_Pain.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Acute_Post-Surgical_Pain.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Acute_Post-Surgical_Pain.html#dataset-geo-gse242389"}],"context_names":["Acute Post-Surgical Pain"],"disease_names":["Acute Post-Surgical Pain"],"disease_name":"Acute Post-Surgical Pain","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Acute_Post-Surgical_Pain.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Acute_Post-Surgical_Pain.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Acute_Post-Surgical_Pain.html#dataset-geo-gse242389"]},{"id":"dataset:geo:gse242414","accession":"geo:GSE242414","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE242414","title":"Single-cell RNA landscape of osteoimmunology microenvironment in Osteoporotic Vertebral Compression Fracture (OVCF) and Kümmell’s Disease (KD)","alternate_titles":[],"description":"Single-cell RNA sequencing of fractured vertebral bone tissue from one OVCF patient and one Kummell disease patient. A total of 8,741 single cells were captured for transcriptomic analysis, identifying mesenchymal stem cells, pericytes, myofibroblasts, fibroblasts, chondrocytes, endothelial cells, granulocytes, monocytes, T cells, B cells, plasma cells, mast cells, and early erythrocytes.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0001075","label":"bony vertebral centrum","display_label":"bony vertebral centrum","url":"http://purl.obolibrary.org/obo/UBERON_0001075"}],"sample_type_labels":["bony vertebral centrum"],"sample_counts":[2],"sample_count":2,"conditions":["osteoporotic vertebral compression fracture","Kummell disease (vertebral avascular necrosis)"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["Illumina NovaSeq 6000"],"platform":"Illumina NovaSeq 6000","publications":["PMID:38161331"],"publication_contexts":[{"context_id":"disorder:Kummell_Disease","publication":"PMID:38161331"}],"publication":"PMID:38161331","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38161331","publication_status":"Publication recorded","findings":[{"statement":"KD tissue shows depletion of mesenchymal stem cells and a relatively suppressed immune system compared to OVCF","evidence":[]},{"statement":"OVCF exhibits higher osteogenic differentiation capacity owing to abundant immune cells","evidence":[]},{"statement":"KD results in greater bone resorption than bone formation, with immune imbalance leading to vertebral avascular necrosis","evidence":[]},{"statement":"CD8-TEM cells and osteoclasts may crosstalk via CD160-TNFRSF14 ligand-receptor interaction","evidence":[]}],"findings_text":["KD tissue shows depletion of mesenchymal stem cells and a relatively suppressed immune system compared to OVCF","OVCF exhibits higher osteogenic differentiation capacity owing to abundant immune cells","KD results in greater bone resorption than bone formation, with immune imbalance leading to vertebral avascular necrosis","CD8-TEM cells and osteoclasts may crosstalk via CD160-TNFRSF14 ligand-receptor interaction"],"evidence":[],"notes":["The only single-cell transcriptomic dataset directly comparing OVCF and Kummell disease tissue. Reveals that transition from OVCF to KD involves MSC depletion and immune suppression, supporting the osteoimmune hypothesis of disease progression."],"contexts":[{"id":"disorder:Kummell_Disease","name":"Kummell Disease","kind":"Disorder","source_path":"kb/disorders/Kummell_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Kummell_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Kummell_Disease.html#dataset-geo-gse242414"}],"context_names":["Kummell Disease"],"disease_names":["Kummell Disease"],"disease_name":"Kummell Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Kummell_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Kummell_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Kummell_Disease.html#dataset-geo-gse242414"]},{"id":"dataset:geo:gse242708","accession":"geo:GSE242708","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE242708","title":"Integrative Gene Regulatory Network Analysis Discloses Key Driver Genes of Fibromuscular Dysplasia in Females: the DEFINE-FMD study","alternate_titles":[],"description":"Fibromuscular dysplasia (FMD) is poorly understood but relatively common vascular disease affecting 3-5% of adult females. 1-3 The pathobiology of FMD involves arterial lesions of stenosis, dissection, tortuosity, dilation and aneurysm which can lead to hypertension, stroke, heart attack and even death. 3-7 While a limited number of gene variants have been associated with FMD,8-12 there are no animal models and few insights as to why this disease occurs.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[8],"sample_count":8,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Fibromuscular Dysplasia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Fibromuscular_Dysplasia","name":"Fibromuscular Dysplasia","kind":"Disorder","source_path":"kb/disorders/Fibromuscular_Dysplasia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fibromuscular_Dysplasia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Fibromuscular_Dysplasia.html#dataset-geo-gse242708"}],"context_names":["Fibromuscular Dysplasia"],"disease_names":["Fibromuscular Dysplasia"],"disease_name":"Fibromuscular Dysplasia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Fibromuscular_Dysplasia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fibromuscular_Dysplasia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Fibromuscular_Dysplasia.html#dataset-geo-gse242708"]},{"id":"dataset:geo:gse242741","accession":"geo:GSE242741","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE242741","title":"Single cell RNA analysis of lung endothelial cells in mouse model of Hereditary Hemorrhagic Telangiectasia 2","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"house mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[2],"sample_count":2,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39429196"],"publication_contexts":[{"context_id":"disorder:Hereditary_Hemorrhagic_Telangiectasia_Type_2","publication":"PMID:39429196"}],"publication":"PMID:39429196","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39429196","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Companion single-cell series from the same Alk1 deletion study; this is the transcriptomic dataset in which the arterial-lymphatic-like endothelial population was identified."],"contexts":[{"id":"disorder:Hereditary_Hemorrhagic_Telangiectasia_Type_2","name":"Hereditary Hemorrhagic Telangiectasia Type 2","kind":"Disorder","source_path":"kb/disorders/Hereditary_Hemorrhagic_Telangiectasia_Type_2.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hereditary_Hemorrhagic_Telangiectasia_Type_2.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hereditary_Hemorrhagic_Telangiectasia_Type_2.html#dataset-geo-gse242741"}],"context_names":["Hereditary Hemorrhagic Telangiectasia Type 2"],"disease_names":["Hereditary Hemorrhagic Telangiectasia Type 2"],"disease_name":"Hereditary Hemorrhagic Telangiectasia Type 2","same_context_model_ids":["model:kb/disorders/Hereditary_Hemorrhagic_Telangiectasia_Type_2.yaml:LUMCi029-A-3 isogenic hiPSC line carrying ACVRL1 c.143G>A (p.Gly48Glu)"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Hereditary_Hemorrhagic_Telangiectasia_Type_2.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hereditary_Hemorrhagic_Telangiectasia_Type_2.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hereditary_Hemorrhagic_Telangiectasia_Type_2.html#dataset-geo-gse242741"]},{"id":"dataset:geo:gse243002","accession":"geo:GSE243002","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE243002","title":"Comprehensive Profiling of Peripheral Blood Mononuclear Cells Reveals Monocyte-CD8+ T cell-B cell Communication as Central Cell-cell Interaction and pathogenesis in IgA Vasculitis","alternate_titles":[],"description":"IgA vasculitis (IgAV) is a common vasculitis which often occurs in children. IgAV is characterized by the vasculitis caused by IgA deposition in the walls of small vessels. The mechanisms of immune disorders in IgAV, as well as the innmue network regulation between immune cells is still unclear. Dissecting the IgA-secreting B cells is crucial for understanding the pathegenesis mechanisms of IgA deposition in IgA vasculitis (IgAV). Here, we used single-cell RNA sequencing to profile immune cells in peripheral blood mononuclear cells of IgAV. MIF induced IgA secretion in IgAV, and monocyte-CD8+ T cell-B cell communication regulated MIF pathway.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[21],"sample_count":21,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41212476"],"publication_contexts":[{"context_id":"disorder:IgA_Vasculitis","publication":"PMID:41212476"}],"publication":"PMID:41212476","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41212476","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for IgA Vasculitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:IgA_Vasculitis","name":"IgA Vasculitis","kind":"Disorder","source_path":"kb/disorders/IgA_Vasculitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/IgA_Vasculitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/IgA_Vasculitis.html#dataset-geo-gse243002"}],"context_names":["IgA Vasculitis"],"disease_names":["IgA Vasculitis"],"disease_name":"IgA Vasculitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/IgA_Vasculitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/IgA_Vasculitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/IgA_Vasculitis.html#dataset-geo-gse243002"]},{"id":"dataset:geo:gse243061","accession":"geo:GSE243061","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE243061","title":"Tregs in autoimmune polyendocrine syndrome type I","alternate_titles":[],"description":"Autoimmune polyendocrine syndrome type 1 (APS-1) relies on failures both in central and peripheral tolerance. A decreased number of regulatory T cells (Tregs) is repeatedly reported, and Tregs based therapy could therefore be considered. We have used a single cell transcriptomic approach to characterize Tregs sorted from blood.","alternate_descriptions":["Single-cell transcriptomic study of regulatory T cells sorted from peripheral blood in four APS-1 participants and four healthy controls, with ex-vivo expansion analyses. GEO notes that raw patient data are withheld for privacy, which limits unrestricted reanalysis."],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"CL:0000815","label":"regulatory T cell","display_label":"regulatory T cell","url":"http://purl.obolibrary.org/obo/CL_0000815"}],"sample_type_labels":["regulatory T cell"],"sample_counts":[8],"sample_count":8,"conditions":["APS-1","Healthy control"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:38632993"],"publication_contexts":[{"context_id":"disorder:Autoimmune_Polyendocrine_Syndrome_Type_1","publication":"PMID:38632993"},{"context_id":"disorder:Autoimmune_Polyendocrinopathy","publication":"PMID:38632993"}],"publication":"PMID:38632993","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38632993","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:38632993","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38632993","reference_title":"Single cell characterization of blood and expanded regulatory T cells in autoimmune polyendocrine syndrome type 1.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"We have used single cell transcriptomics to characterize regulatory T cells (Tregs) sorted directly from blood and from in vitro expanded Tregs in APS-1 patients compared to healthy controls.","explanation":"The publication directly describes the dataset's cell population, assay, and comparison."}],"notes":["Identified by GEO DataSets index search for Autoimmune Polyendocrine Syndrome Type 1 (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.","https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE243061"],"contexts":[{"id":"disorder:Autoimmune_Polyendocrine_Syndrome_Type_1","name":"Autoimmune Polyendocrine Syndrome Type 1","kind":"Disorder","source_path":"kb/disorders/Autoimmune_Polyendocrine_Syndrome_Type_1.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autoimmune_Polyendocrine_Syndrome_Type_1.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autoimmune_Polyendocrine_Syndrome_Type_1.html#dataset-geo-gse243061"},{"id":"disorder:Autoimmune_Polyendocrinopathy","name":"Autoimmune Polyendocrinopathy","kind":"Disorder","source_path":"kb/disorders/Autoimmune_Polyendocrinopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autoimmune_Polyendocrinopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autoimmune_Polyendocrinopathy.html#dataset-geo-gse243061"}],"context_names":["Autoimmune Polyendocrine Syndrome Type 1","Autoimmune Polyendocrinopathy"],"disease_names":["Autoimmune Polyendocrine Syndrome Type 1","Autoimmune Polyendocrinopathy"],"disease_name":"Autoimmune Polyendocrine Syndrome Type 1","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Autoimmune_Polyendocrine_Syndrome_Type_1.yaml","kb/disorders/Autoimmune_Polyendocrinopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autoimmune_Polyendocrine_Syndrome_Type_1.yaml","https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autoimmune_Polyendocrinopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Autoimmune_Polyendocrine_Syndrome_Type_1.html#dataset-geo-gse243061","https://dismech.monarchinitiative.org/pages/disorders/Autoimmune_Polyendocrinopathy.html#dataset-geo-gse243061"]},{"id":"dataset:geo:gse243689","accession":"geo:GSE243689","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE243689","title":"Ankylosing spondylitis patients present a distinct CD8 T-cell subset with osteogenic and cytotoxic potential","alternate_titles":[],"description":"Ankylosing Spondylitis (AS) is a chronic inflammatory rheumatic disease affecting mainly the axial skeleton. Peripheral involvement (arthritis, enthesitis and dactylitis) and extra-musculoskeletal manifestations including uveitis, psoriasis and bowel inflammation occur in a relevant proportion of patients. AS is responsible for chronic and severe back pain caused by local inflammation that can lead to osteoproliferation and ultimately spinal fusion. The association of AS with the Human Leukocyte Antigen (HLA)‑B27 gene, together with elevated levels of chemokines CCL17 and CCL22 in the sera of patients with AS, lead us to study the role of CCR4+ T-cells in the disease pathogenesis.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[11],"sample_count":11,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:38395454"],"publication_contexts":[{"context_id":"disorder:Ankylosing_Spondylitis","publication":"PMID:38395454"}],"publication":"PMID:38395454","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38395454","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Ankylosing Spondylitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Ankylosing_Spondylitis","name":"Ankylosing Spondylitis","kind":"Disorder","source_path":"kb/disorders/Ankylosing_Spondylitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ankylosing_Spondylitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Ankylosing_Spondylitis.html#dataset-geo-gse243689"}],"context_names":["Ankylosing Spondylitis"],"disease_names":["Ankylosing Spondylitis"],"disease_name":"Ankylosing Spondylitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Ankylosing_Spondylitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ankylosing_Spondylitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Ankylosing_Spondylitis.html#dataset-geo-gse243689"]},{"id":"dataset:geo:gse243874","accession":"geo:GSE243874","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE243874","title":"An RNA-seq study in Friedreich ataxia patients identified miR148a-3p as a putative prognostic biomarker of the disease.","alternate_titles":[],"description":"Small non-coding RNA sequencing of peripheral blood mononuclear cells from FRDA patients and healthy donors, used to nominate circulating microRNA biomarkers of disease progression.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[16],"sample_count":16,"conditions":["Friedreich ataxia PBMC","healthy donor PBMC"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:38778374"],"publication_contexts":[{"context_id":"disorder:Friedreich_Ataxia","publication":"PMID:38778374"}],"publication":"PMID:38778374","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38778374","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE243874","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE243874","reference_title":"An RNA-seq study in Friedreich ataxia patients identified miR148a-3p as a putative prognostic biomarker of the disease.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"We performed an RNA-seq study evaluating the expression level of circulating small non-coding RNAs (sncRNA) on PBMCs of FRDA patients and of healthy donors (CTRL).","explanation":"The GEO summary establishes the patient-versus-control circulating sncRNA design of this series."}],"notes":[],"contexts":[{"id":"disorder:Friedreich_Ataxia","name":"Friedreich Ataxia","kind":"Disorder","source_path":"kb/disorders/Friedreich_Ataxia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Friedreich_Ataxia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Friedreich_Ataxia.html#dataset-geo-gse243874"}],"context_names":["Friedreich Ataxia"],"disease_names":["Friedreich Ataxia"],"disease_name":"Friedreich Ataxia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Friedreich_Ataxia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Friedreich_Ataxia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Friedreich_Ataxia.html#dataset-geo-gse243874"]},{"id":"dataset:geo:gse244010","accession":"geo:GSE244010","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE244010","title":"Aberrant pace of cortical neuron development in brain organoids from patients with 22q11.2 deletion syndrome and schizophrenia.","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[26],"sample_count":26,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40750773"],"publication_contexts":[{"context_id":"disorder:22q11.2_Deletion_Syndrome","publication":"PMID:40750773"}],"publication":"PMID:40750773","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40750773","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for 22q11.2 Deletion Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:22q11.2_Deletion_Syndrome","name":"22q11.2 Deletion Syndrome","kind":"Disorder","source_path":"kb/disorders/22q11.2_Deletion_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/22q11.2_Deletion_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/22q11.2_Deletion_Syndrome.html#dataset-geo-gse244010"}],"context_names":["22q11.2 Deletion Syndrome"],"disease_names":["22q11.2 Deletion Syndrome"],"disease_name":"22q11.2 Deletion Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/22q11.2_Deletion_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/22q11.2_Deletion_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/22q11.2_Deletion_Syndrome.html#dataset-geo-gse244010"]},{"id":"dataset:geo:gse244463","accession":"geo:GSE244463","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE244463","title":"Identifying new cellular mechanisms of MCPH5","alternate_titles":[],"description":"Developmental brain transcriptomes from Drosophila asp mutants, rescue animals, and wild-type controls across larval, pupal, and adult stages.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:7227","label":"Drosophila melanogaster","display_label":"fruit fly","url":"http://purl.obolibrary.org/obo/NCBITaxon_7227"}],"organism_labels":["Drosophila melanogaster"],"organism_label":"Drosophila melanogaster","sample_types":[],"sample_type_labels":[],"sample_counts":[36],"sample_count":36,"conditions":["asp mutant","asp rescue","Wild-type control"],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:19048","label":"ASPM","display_label":"ASPM","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/19048"}],"genes":["ASPM"],"platforms":[],"platform":null,"publications":["PMID:37831641"],"publication_contexts":[{"context_id":"disorder:Autosomal_Recessive_Primary_Microcephaly","publication":"PMID:37831641"}],"publication":"PMID:37831641","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37831641","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:37831641","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/37831641","reference_title":"Mutations in abnormal spindle disrupt temporal transcription factor expression and trigger immune responses in the Drosophila brain.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"we provide the neurodevelopmental transcriptional landscape for a Drosophila model for autosomal recessive primary microcephaly-5 (MCPH5)","explanation":"The associated publication defines the transcriptomic MCPH5 model."}],"notes":[],"contexts":[{"id":"disorder:Autosomal_Recessive_Primary_Microcephaly","name":"Autosomal Recessive Primary Microcephaly","kind":"Disorder","source_path":"kb/disorders/Autosomal_Recessive_Primary_Microcephaly.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autosomal_Recessive_Primary_Microcephaly.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Recessive_Primary_Microcephaly.html#dataset-geo-gse244463"}],"context_names":["Autosomal Recessive Primary 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In this study, we aimed to elucidate the pathophysiological changes in patients with CeAD and identify biomarkers.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[10],"sample_count":10,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Cervical Artery Dissection (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Cervical_Artery_Dissection","name":"Cervical Artery Dissection","kind":"Disorder","source_path":"kb/disorders/Cervical_Artery_Dissection.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cervical_Artery_Dissection.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cervical_Artery_Dissection.html#dataset-geo-gse244467"}],"context_names":["Cervical Artery Dissection"],"disease_names":["Cervical Artery Dissection"],"disease_name":"Cervical Artery Dissection","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cervical_Artery_Dissection.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cervical_Artery_Dissection.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cervical_Artery_Dissection.html#dataset-geo-gse244467"]},{"id":"dataset:geo:gse244781","accession":"geo:GSE244781","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE244781","title":"Molecular changes implicate angiogenesis and arterial remodeling in systemic sclerosis-associated and idiopathic pulmonary hypertension","alternate_titles":[],"description":"Single-cell transcriptomic comparison of pulmonary vascular populations in systemic-sclerosis-associated and idiopathic pulmonary hypertension against control lung.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[33],"sample_count":33,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:38841857"],"publication_contexts":[{"context_id":"disorder:Idiopathic_Pulmonary_Arterial_Hypertension","publication":"PMID:38841857"}],"publication":"PMID:38841857","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38841857","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Relevance triage: DIRECT but mixed-cohort. The series pools SSc-associated pulmonary hypertension with idiopathic PAH, so the IPAH samples must be separated before the data speak to this entry; the SSc arm belongs to associated PAH, not here. Recorded with that caveat rather than dropped, because the case-control contrast is against the same control lungs. GEO labels the series type as expression profiling by high-throughput sequencing. Accession resolved 2026-09-03."],"contexts":[{"id":"disorder:Idiopathic_Pulmonary_Arterial_Hypertension","name":"Idiopathic Pulmonary Arterial Hypertension","kind":"Disorder","source_path":"kb/disorders/Idiopathic_Pulmonary_Arterial_Hypertension.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Idiopathic_Pulmonary_Arterial_Hypertension.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Idiopathic_Pulmonary_Arterial_Hypertension.html#dataset-geo-gse244781"}],"context_names":["Idiopathic Pulmonary Arterial Hypertension"],"disease_names":["Idiopathic Pulmonary Arterial Hypertension"],"disease_name":"Idiopathic Pulmonary Arterial Hypertension","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Idiopathic_Pulmonary_Arterial_Hypertension.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Idiopathic_Pulmonary_Arterial_Hypertension.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Idiopathic_Pulmonary_Arterial_Hypertension.html#dataset-geo-gse244781"]},{"id":"dataset:geo:gse244853","accession":"geo:GSE244853","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE244853","title":"Development of serum cell-free miRNA panel for identification of girlish central precocious puberty and premature thelarche","alternate_titles":[],"description":"Seek and verify the effectiveness of a subset of cell-free miRNA to identify CPP and PT","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[88],"sample_count":88,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Central Precocious Puberty (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Central_Precocious_Puberty","name":"Central Precocious Puberty","kind":"Disorder","source_path":"kb/disorders/Central_Precocious_Puberty.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Central_Precocious_Puberty.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Central_Precocious_Puberty.html#dataset-geo-gse244853"}],"context_names":["Central Precocious Puberty"],"disease_names":["Central Precocious Puberty"],"disease_name":"Central Precocious Puberty","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Central_Precocious_Puberty.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Central_Precocious_Puberty.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Central_Precocious_Puberty.html#dataset-geo-gse244853"]},{"id":"dataset:geo:gse245093","accession":"geo:GSE245093","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE245093","title":"Mini-heterochromatin domains constrain the cis-regulatory impact of SVA transposons in human brain development and disease","alternate_titles":[],"description":"Human neural-progenitor methylation and chromatin data underlying the ZNF91-dependent SVA mini-heterochromatin model.","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[143],"sample_count":143,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:38834915"],"publication_contexts":[{"context_id":"disorder:X-linked_Dystonia-Parkinsonism","publication":"PMID:38834915"}],"publication":"PMID:38834915","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38834915","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified and metadata-verified with scripts/discover_datasets.py on 2026-08-11."],"contexts":[{"id":"disorder:X-linked_Dystonia-Parkinsonism","name":"X-linked Dystonia-Parkinsonism","kind":"Disorder","source_path":"kb/disorders/X-linked_Dystonia-Parkinsonism.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/X-linked_Dystonia-Parkinsonism.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/X-linked_Dystonia-Parkinsonism.html#dataset-geo-gse245093"}],"context_names":["X-linked Dystonia-Parkinsonism"],"disease_names":["X-linked Dystonia-Parkinsonism"],"disease_name":"X-linked Dystonia-Parkinsonism","same_context_model_ids":["model:kb/disorders/X-linked_Dystonia-Parkinsonism.yaml:Human neural-progenitor SVA mini-heterochromatin model","model:kb/disorders/X-linked_Dystonia-Parkinsonism.yaml:Isogenic XDP striatal organoid repeat-RNA model","model:kb/disorders/X-linked_Dystonia-Parkinsonism.yaml:Patient-derived fibroblast and neural-progenitor G-quadruplex model","model:kb/disorders/X-linked_Dystonia-Parkinsonism.yaml:XDP iPSC-derived neural stem cells and medium spiny neurons","model:kb/disorders/X-linked_Dystonia-Parkinsonism.yaml:XDP iPSC-derived neuronal lineages with CRISPR SVA excision"],"candidate_model_ids":["model:kb/disorders/X-linked_Dystonia-Parkinsonism.yaml:Human neural-progenitor SVA mini-heterochromatin model"],"association_basis":"Same publication as a NAM (candidate)","nam_disease_context":"Same publication as a NAM (candidate)","source_paths":["kb/disorders/X-linked_Dystonia-Parkinsonism.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/X-linked_Dystonia-Parkinsonism.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/X-linked_Dystonia-Parkinsonism.html#dataset-geo-gse245093"]},{"id":"dataset:geo:gse245228","accession":"geo:GSE245228","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE245228","title":"Compartment-specific small RNA sequencing profile of Hippocampal and Cortical cells from Mesial Temporal Lobe Epilepsy tissue","alternate_titles":[],"description":"Mesial temporal lobe epilepsy (mTLE) is a chronic neurological disease characterized by recurrent seizures. The pathogenic mechanisms underlying TLE involve defects in post-transcriptional regulation of gene expression. Previously we have shown the differences in cell compartment specific differential expression of coding transcripts in mTLE hippocampal and cortical samples compared to post-mortem controls (Vangoor et al., MedRxiv. 2021).","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[68],"sample_count":68,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39509000"],"publication_contexts":[{"context_id":"disorder:Mesial_Temporal_Lobe_Epilepsy_with_Hippocampal_Sclerosis","publication":"PMID:39509000"}],"publication":"PMID:39509000","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39509000","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Mesial_Temporal_Lobe_Epilepsy_with_Hippocampal_Sclerosis","name":"Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis","kind":"Disorder","source_path":"kb/disorders/Mesial_Temporal_Lobe_Epilepsy_with_Hippocampal_Sclerosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mesial_Temporal_Lobe_Epilepsy_with_Hippocampal_Sclerosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Mesial_Temporal_Lobe_Epilepsy_with_Hippocampal_Sclerosis.html#dataset-geo-gse245228"}],"context_names":["Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis"],"disease_names":["Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis"],"disease_name":"Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Mesial_Temporal_Lobe_Epilepsy_with_Hippocampal_Sclerosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mesial_Temporal_Lobe_Epilepsy_with_Hippocampal_Sclerosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Mesial_Temporal_Lobe_Epilepsy_with_Hippocampal_Sclerosis.html#dataset-geo-gse245228"]},{"id":"dataset:geo:gse245639","accession":"geo:GSE245639","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE245639","title":"VEXAS syndrome, myelodysplasia cutis and sweet syndrome skin lesions share a common transcriptomic profile led by interferon signaling","alternate_titles":[],"description":"VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a recently described monogenic disease of adult men cause by somatic mutations in UBA1 in hematopoietic progenitor cells. It associates inflammatory-related symptoms, frequently involving the skin, and hematologic disorders. Myelodysplasia cutis, also recently described, is a cutaneous manifestation of myelodysplasia in which clonal myeloid cells infiltrate the skin. In both cases, skin lesions are due to the infiltration of clonal mutated myeloid cells and may clinically and histologically resemble sweet syndrome, a non-clonal neutrophilic skin disease.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[25],"sample_count":25,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40072458"],"publication_contexts":[{"context_id":"disorder:Sweet_Syndrome","publication":"PMID:40072458"}],"publication":"PMID:40072458","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40072458","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Sweet Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Sweet_Syndrome","name":"Sweet Syndrome","kind":"Disorder","source_path":"kb/disorders/Sweet_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sweet_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Sweet_Syndrome.html#dataset-geo-gse245639"}],"context_names":["Sweet Syndrome"],"disease_names":["Sweet Syndrome"],"disease_name":"Sweet Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Sweet_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sweet_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Sweet_Syndrome.html#dataset-geo-gse245639"]},{"id":"dataset:geo:gse245791","accession":"geo:GSE245791","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE245791","title":"Efficient and Safe Therapeutic Use of Paired Cas9-Nickases for Primary Hyperoxaluria Type 1","alternate_titles":[],"description":"The therapeutic use of adeno-associated viral vector (AAV)-mediated gene disruption using CRISPR-Cas9 is limited by potential off-target modifications and the risk of uncontrolled integration of vector genomes into CRISPR-mediated double-strand breaks. To address these concerns, we explored the use of AAV-delivered paired Staphylococcus aureus nickases (D10ASaCas9) to target the Hao1 gene for the treatment of primary hyperoxaluria type 1 (PH1). Our study demonstrated effective Hao1 gene disruption, a significant decrease in glycolate oxidase expression, and a therapeutic effect in PH1 mice.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[14],"sample_count":14,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:38182795"],"publication_contexts":[{"context_id":"disorder:Primary_Hyperoxaluria_Type_1","publication":"PMID:38182795"}],"publication":"PMID:38182795","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38182795","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Primary Hyperoxaluria Type 1 (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Primary_Hyperoxaluria_Type_1","name":"Primary Hyperoxaluria Type 1","kind":"Disorder","source_path":"kb/disorders/Primary_Hyperoxaluria_Type_1.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Primary_Hyperoxaluria_Type_1.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Hyperoxaluria_Type_1.html#dataset-geo-gse245791"}],"context_names":["Primary Hyperoxaluria Type 1"],"disease_names":["Primary Hyperoxaluria Type 1"],"disease_name":"Primary Hyperoxaluria Type 1","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Primary_Hyperoxaluria_Type_1.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Primary_Hyperoxaluria_Type_1.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Primary_Hyperoxaluria_Type_1.html#dataset-geo-gse245791"]},{"id":"dataset:geo:gse245825","accession":"geo:GSE245825","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE245825","title":"Cardiac Fibrosis in Dilated Cardiomyopathy: Transcriptomics Insights, Histological Correlations, and Organoid Model Verifications [RNA-seq I]","alternate_titles":[],"description":"Dilated cardiomyopathy (DCM) represents a leading cause of heart failure among younger adults. Despite endomyocardial biopsy (EMB) transcriptome enriching our understanding of DCM, the link between its gene expression and phenotype remains unclear. RNA-seq analysis of 58 DCM samples and 12 publicly available control samples unveiled about 25,000 transcripts. A principal component analysis highlighted a distinct DCM-control separation. WGCNA revealed four transcriptome modules strongly associated with DCM. The purple module, which is the DCM-related module, was enriched with fibrosis-related genes and showed FSTL3 as a pivotal DCM-associated gene.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[58],"sample_count":58,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40934809"],"publication_contexts":[{"context_id":"disorder:Dilated_Cardiomyopathy","publication":"PMID:40934809"}],"publication":"PMID:40934809","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40934809","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Dilated Cardiomyopathy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Dilated_Cardiomyopathy","name":"Dilated Cardiomyopathy","kind":"Disorder","source_path":"kb/disorders/Dilated_Cardiomyopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dilated_Cardiomyopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy.html#dataset-geo-gse245825"}],"context_names":["Dilated Cardiomyopathy"],"disease_names":["Dilated Cardiomyopathy"],"disease_name":"Dilated Cardiomyopathy","same_context_model_ids":["model:kb/disorders/Dilated_Cardiomyopathy.yaml:Patient-specific TNNT2 R173W iPSC-derived cardiomyocytes (Clinical Trials in a Dish)"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Dilated_Cardiomyopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dilated_Cardiomyopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy.html#dataset-geo-gse245825"]},{"id":"dataset:geo:gse245916","accession":"geo:GSE245916","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE245916","title":"Species-specific responses during Seoul orthohantavirus infection in human and rat lung microvascular endothelial cells","alternate_titles":[],"description":"Paired transcriptional profiling of primary human and rat lung microvascular endothelial cells infected with Seoul orthohantavirus, the agent of a milder form of HFRS. The comparison is the point: the same infection is acute disease in humans and a persistent, asymptomatic infection in the reservoir rat, so the divergent endothelial host response bears directly on why the microvascular barrier fails only in the human host.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[24],"sample_count":24,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:38536871"],"publication_contexts":[{"context_id":"disorder:Hantavirus_Hemorrhagic_Fever_with_Renal_Syndrome","publication":"PMID:38536871"}],"publication":"PMID:38536871","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38536871","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Relocated from the retired Viral_Hemorrhagic_Fever umbrella entry (issue dismech#10115), where it had been indexed under the umbrella by scripts/discover_datasets.py; it is a Seoul-orthohantavirus HFRS dataset and belongs on this entry. Accession and metadata were verified against NCBI E-utilities on 2026-08-01 when first added. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Hantavirus_Hemorrhagic_Fever_with_Renal_Syndrome","name":"Hantavirus Hemorrhagic Fever with Renal Syndrome","kind":"Disorder","source_path":"kb/disorders/Hantavirus_Hemorrhagic_Fever_with_Renal_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hantavirus_Hemorrhagic_Fever_with_Renal_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hantavirus_Hemorrhagic_Fever_with_Renal_Syndrome.html#dataset-geo-gse245916"}],"context_names":["Hantavirus Hemorrhagic Fever with Renal Syndrome"],"disease_names":["Hantavirus Hemorrhagic Fever with Renal Syndrome"],"disease_name":"Hantavirus Hemorrhagic Fever with Renal Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hantavirus_Hemorrhagic_Fever_with_Renal_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hantavirus_Hemorrhagic_Fever_with_Renal_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hantavirus_Hemorrhagic_Fever_with_Renal_Syndrome.html#dataset-geo-gse245916"]},{"id":"dataset:geo:gse245935","accession":"geo:GSE245935","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE245935","title":"Chemo-senolytic therapeutic potential against angiosarcoma","alternate_titles":[],"description":"Angiosarcoma is an aggressive soft-tissue sarcoma with a poor prognosis. Chemotherapy for this cancer typically employs paclitaxel, one of the taxanes (genotoxic drugs), although it has a limited effect due to chemoresistance for prolonged treatment. Here we examine a new angiosarcoma treatment approach that combines chemotherapeutic and senolytic agents. We first find that the chemotherapeutic drugs, cisplatin and paclitaxel, efficiently induce cellular senescence of angiosarcoma cells. Subsequent treatment with a senolytic agent, ABT-263, eliminates senescent cells through the activation of the apoptotic pathway.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[13],"sample_count":13,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:38570028"],"publication_contexts":[{"context_id":"disorder:Angiosarcoma","publication":"PMID:38570028"}],"publication":"PMID:38570028","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38570028","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Angiosarcoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Angiosarcoma","name":"Angiosarcoma","kind":"Disorder","source_path":"kb/disorders/Angiosarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Angiosarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Angiosarcoma.html#dataset-geo-gse245935"}],"context_names":["Angiosarcoma"],"disease_names":["Angiosarcoma"],"disease_name":"Angiosarcoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Angiosarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Angiosarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Angiosarcoma.html#dataset-geo-gse245935"]},{"id":"dataset:geo:gse246097","accession":"geo:GSE246097","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE246097","title":"Integration of miRNA in exosomes and single-cell RNA-seq profiles in endemic osteoarthritis, Kashin-Beck disease","alternate_titles":[],"description":"Serum and chondrocyte exosomal miRNA sequencing integrated with single-cell RNA-seq of patient chondrocytes - the only single-cell resource this session identified for the disease. Typed MULTI_OMICS because it is two assay types analysed together rather than either one alone.","alternate_descriptions":[],"data_types":["MULTI_OMICS"],"data_type_labels":["Multi Omics"],"data_type_label":"Multi Omics","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:38156801"],"publication_contexts":[{"context_id":"disorder:Kashin-Beck_Disease","publication":"PMID:38156801"}],"publication":"PMID:38156801","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38156801","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE246097","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE246097","reference_title":"Integration of miRNA in exosomes and single-cell RNA-seq profiles in endemic osteoarthritis, Kashin-Beck disease","supports":"SUPPORT","evidence_source":"OTHER","snippet":"We isolated serum and chondrocytes-derived exosomes, miRNA sequencing revealed exosomes miRNA profiles and differentially expressed miRNAs (DE-miRNAs) were identified.","explanation":"The exosomal miRNA half of the series, from GEO's own summary. Graded OTHER: a repository record describing its contents, not a study result."},{"reference":"GEO:GSE246097","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE246097","reference_title":"Integration of miRNA in exosomes and single-cell RNA-seq profiles in endemic osteoarthritis, Kashin-Beck disease","supports":"SUPPORT","evidence_source":"OTHER","snippet":"Single-cell RNA sequencing (scRNA-seq) was performed to identify chondrocyte clusters and their gene signatures in KBD.","explanation":"The single-cell half, which is what makes this series the only one of its kind here."}],"notes":[],"contexts":[{"id":"disorder:Kashin-Beck_Disease","name":"Kashin-Beck Disease","kind":"Disorder","source_path":"kb/disorders/Kashin-Beck_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Kashin-Beck_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Kashin-Beck_Disease.html#dataset-geo-gse246097"}],"context_names":["Kashin-Beck Disease"],"disease_names":["Kashin-Beck Disease"],"disease_name":"Kashin-Beck Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Kashin-Beck_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Kashin-Beck_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Kashin-Beck_Disease.html#dataset-geo-gse246097"]},{"id":"dataset:geo:gse246204","accession":"geo:GSE246204","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE246204","title":"miRNA and mRNA Signatures in Human Acute Kidney Injury Tissue [mRNA, minimal change disease]","alternate_titles":[],"description":"Acute kidney injury (AKI) is an important contributor to the development of chronic kidney disease (CKD). We performed miRNA and mRNA sequencing on biobanked human kidney tissues obtained in the routine clinical care of patients with the diagnoses of AKI and minimal change disease (MCD), in addition to nephrectomized (Ref) tissue from individuals without known kidney disease. From all renal biopsy samples, 2 cryosections (10 μM) including the entire cross-section of the tissue were placed directly into PicoPure RNA extraction buffer. RNA was isolated using the PicoPure isolation kit. Total RNA was evaluated for quantity and quality using an Agilent Bioanalyzer.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:38954486"],"publication_contexts":[{"context_id":"disorder:Minimal_Change_Disease","publication":"PMID:38954486"}],"publication":"PMID:38954486","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38954486","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Minimal Change Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Minimal_Change_Disease","name":"Minimal Change Disease","kind":"Disorder","source_path":"kb/disorders/Minimal_Change_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Minimal_Change_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Minimal_Change_Disease.html#dataset-geo-gse246204"}],"context_names":["Minimal Change Disease"],"disease_names":["Minimal Change Disease"],"disease_name":"Minimal Change Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Minimal_Change_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Minimal_Change_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Minimal_Change_Disease.html#dataset-geo-gse246204"]},{"id":"dataset:geo:gse246398","accession":"geo:GSE246398","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE246398","title":"BIOLOGICAL EFFECTS OF CORTICOSTEROIDS ON PNEUMOCOCCAL PNEUMONIA IN MICE AND HUMANS","alternate_titles":[],"description":"Rationale: Streptococcus pneumoniae is the most common bacterial cause of community acquired pneumonia. Some clinical trials have demonstrated a beneficial effect of corticosteroid therapy in community acquired pneumonia, but the mechanisms of this benefit remain unclear. Objectives: To investigate the biologic effects of corticosteroids in pneumococcal pneumonia in mice and in patients Methods: We studied lower respiratory tract transcriptomes from an observational cohort of mechanically ventilated patients and from a pneumonia model in mice. We also carried out comprehensive physiologic, biochemical, and histological analyses in mice to identify mechanisms of lung injury in S.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[15],"sample_count":15,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:38807178"],"publication_contexts":[{"context_id":"disorder:Pneumococcal_Pneumonia","publication":"PMID:38807178"}],"publication":"PMID:38807178","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38807178","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Pneumococcal Pneumonia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Pneumococcal_Pneumonia","name":"Pneumococcal Pneumonia","kind":"Disorder","source_path":"kb/disorders/Pneumococcal_Pneumonia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pneumococcal_Pneumonia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pneumococcal_Pneumonia.html#dataset-geo-gse246398"}],"context_names":["Pneumococcal Pneumonia"],"disease_names":["Pneumococcal Pneumonia"],"disease_name":"Pneumococcal Pneumonia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Pneumococcal_Pneumonia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pneumococcal_Pneumonia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Pneumococcal_Pneumonia.html#dataset-geo-gse246398"]},{"id":"dataset:geo:gse247134","accession":"geo:GSE247134","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE247134","title":"Single cell transcriptomics of cerebrospinal fluid cells from patients with recent-onset narcolepsy","alternate_titles":[],"description":"Narcolepsy is a rare cause of excessive daytime sleepiness and may be associated or not with cataplexy, i.e. sudden muscle weakness. These forms are designated NAR-type 1 (NT1) and -type 2 (NT2), respectively. Notable characteristics of narcolepsy are that most patients carry the HLA-DQB1*06:02 allele and NT1-patients have highly decreased levels hypocretin-1 (synonym orexin-A) in the cerebrospinal fluid (CSF). The pathogenesis of narcolepsy is still enigmatic but the strung HLA-bias and increased frequencies of CD4+ T cells reactive to hypocretin in the peripheral blood suggest autoimmune processes in the hypothalamus.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[48],"sample_count":48,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Narcolepsy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Narcolepsy","name":"Narcolepsy","kind":"Disorder","source_path":"kb/disorders/Narcolepsy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Narcolepsy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Narcolepsy.html#dataset-geo-gse247134"}],"context_names":["Narcolepsy"],"disease_names":["Narcolepsy"],"disease_name":"Narcolepsy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Narcolepsy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Narcolepsy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Narcolepsy.html#dataset-geo-gse247134"]},{"id":"dataset:geo:gse247274","accession":"geo:GSE247274","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE247274","title":"Unstableregulatory and autoreactive effector T cells in patients with FOXP3 mutations","alternate_titles":[],"description":"Studies of the monogenic autoimmune disease immunodysregulation polyendocrinopathy enteropathy X-linked syndrome (IPEX) have elucidated the essential function of the transcription factor FOXP3 and thymic-derived regulatory T cells (Tregs) in controlling peripheral tolerance. However, the presence and the source of autoreactive T cells in IPEX remain undetermined. Here, we investigated how FOXP3 deficiency affects the T cell receptor (TCR) repertoire and Treg stability in vivo and compared T cell abnormalities in patients with IPEX to those in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED).","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[18],"sample_count":18,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:38117899"],"publication_contexts":[{"context_id":"disorder:Autoimmune_Enteropathy","publication":"PMID:38117899"}],"publication":"PMID:38117899","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38117899","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Autoimmune Enteropathy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Autoimmune_Enteropathy","name":"Autoimmune Enteropathy","kind":"Disorder","source_path":"kb/disorders/Autoimmune_Enteropathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autoimmune_Enteropathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autoimmune_Enteropathy.html#dataset-geo-gse247274"}],"context_names":["Autoimmune Enteropathy"],"disease_names":["Autoimmune Enteropathy"],"disease_name":"Autoimmune Enteropathy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Autoimmune_Enteropathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autoimmune_Enteropathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Autoimmune_Enteropathy.html#dataset-geo-gse247274"]},{"id":"dataset:geo:gse247473","accession":"geo:GSE247473","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE247473","title":"Therapeutic Restoration of miR-96 Prevents Hearing Loss in Mice through Modulation of Noise-Induced and Genetic Pathways","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:31648","label":"MIR96","display_label":"MIR96","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/31648"}],"genes":["MIR96"],"platforms":[],"platform":null,"publications":["PMID:40641557"],"publication_contexts":[{"context_id":"disorder:Autosomal_Dominant_Nonsyndromic_Hearing_Loss_50","publication":"PMID:40641557"}],"publication":"PMID:40641557","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40641557","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:40641557","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40641557","reference_title":"Therapeutic restoration of miR-96 prevents hearing loss in mice through modulation of noise-induced and genetic pathways.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"The RNA-seq raw data as well as gene read counts for individual sample are accessible at Gene Expression Omnibus under accession number GSE247473.","explanation":"Verifies the accession-publication link; methods define the two knockout comparisons."}],"notes":["Whole-cochlea transcriptomes from P28 constitutive Mir96 knockout versus wild-type mice (four per group), and adult inducible knockout versus control mice four weeks after tamoxifen (four knockout and three control samples). The paper also reports AAV rescue experiments, but those interventions are not the RNA-seq comparisons described here. Loss-of-function comparators do not reproduce the acquired target set of dominant seed variants."],"contexts":[{"id":"disorder:Autosomal_Dominant_Nonsyndromic_Hearing_Loss_50","name":"Autosomal Dominant Nonsyndromic Hearing Loss 50","kind":"Disorder","source_path":"kb/disorders/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_50.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_50.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_50.html#dataset-geo-gse247473"}],"context_names":["Autosomal Dominant Nonsyndromic Hearing Loss 50"],"disease_names":["Autosomal Dominant Nonsyndromic Hearing Loss 50"],"disease_name":"Autosomal Dominant Nonsyndromic Hearing Loss 50","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_50.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_50.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_50.html#dataset-geo-gse247473"]},{"id":"dataset:geo:gse247506","accession":"geo:GSE247506","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE247506","title":"Peripheral blood transcriptomic analysis identifies potential inflammation and immune signatures for central retinal artery occlusion","alternate_titles":[],"description":"Central retinal artery occlusion (CRAO) is an acute retinal ischaemic disease, but early diagnosis is challenging due to a lack of biomarkers. Blood samples were collected from CRAO patients and cataract patients. Gene expression profiles were distinct between arterial/venous CRAO blood (A-V group) and venous CRAO/control blood (V-C group) samples. Differentially expressed genes (DEGs) were subjected to GO and KEGG enrichment analyses. Hub genes were identified by Cytoscape and used to predict gene interactions via GeneMANIA. Immune cell infiltration was analysed by CIBERSORT. More than 1400 DEGs were identified in the A-V group and 112 DEGs in the V-C group compared to controls.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[25],"sample_count":25,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:38548806"],"publication_contexts":[{"context_id":"disorder:Central_Retinal_Artery_Occlusion","publication":"PMID:38548806"}],"publication":"PMID:38548806","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38548806","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Central Retinal Artery Occlusion (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Central_Retinal_Artery_Occlusion","name":"Central Retinal Artery Occlusion","kind":"Disorder","source_path":"kb/disorders/Central_Retinal_Artery_Occlusion.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Central_Retinal_Artery_Occlusion.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Central_Retinal_Artery_Occlusion.html#dataset-geo-gse247506"}],"context_names":["Central Retinal Artery Occlusion"],"disease_names":["Central Retinal Artery Occlusion"],"disease_name":"Central Retinal Artery Occlusion","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association 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recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:38858384","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38858384","reference_title":"Retrotransposons in Werner syndrome-derived macrophages trigger type I interferon-dependent inflammation in an atherosclerosis model.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"RNA-sequencing (seq) and assay for transposase-accessible chromatin using sequencing (ATAC-seq) reveal accelerated type I IFN signaling and reduced chromatin accessibility in WS-iMφs.","explanation":"The publication describes the core omics assays represented by the superseries."}],"notes":["Identified by GEO discovery and verified against NCBI E-utilities on 2026-08-24; GEO reports Homo sapiens, 97 samples, and PMID:38858384."],"contexts":[{"id":"disorder:Werner_Syndrome","name":"Werner 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(candidate)","source_paths":["kb/disorders/Werner_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Werner_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Werner_Syndrome.html#dataset-geo-gse247722"]},{"id":"dataset:geo:gse247838","accession":"geo:GSE247838","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE247838","title":"Transcriptional reprogramming of neural stem cells by a PHF6/EphR signalling pathway","alternate_titles":[],"description":"Disease-mechanism dataset associated with the PHF6-Ephrin-receptor study, combining PHF6 cortical ChIP-seq with bulk RNA-seq after Phf6 knockdown in embryonic mouse cortical progenitors.","alternate_descriptions":[],"data_types":["MULTI_OMICS_PERTURBATION"],"data_type_labels":["Multi Omics Perturbation"],"data_type_label":"Multi Omics Perturbation","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[{"id":"UBERON:0000956","label":"cerebral cortex","display_label":"cerebral cortex","url":"http://purl.obolibrary.org/obo/UBERON_0000956"},{"id":"CL:0000047","label":"neural stem cell","display_label":"neural stem cell","url":"http://purl.obolibrary.org/obo/CL_0000047"}],"sample_type_labels":["cerebral cortex","neural stem cell"],"sample_counts":[],"sample_count":null,"conditions":["PHF6 cortical chromatin immunoprecipitation and IgG control","Phf6 siRNA knockdown and non-targeting control in embryonic cortical progenitors"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["DOI:10.1038/s44319-024-00082-0"],"publication_contexts":[{"context_id":"disorder:Borjeson-Forssman-Lehmann_syndrome","publication":"DOI:10.1038/s44319-024-00082-0"}],"publication":"DOI:10.1038/s44319-024-00082-0","publication_url":null,"publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"DOI:10.1038/s44319-024-00082-0","reference_url":null,"reference_title":"PHF6-mediated transcriptional control of NSC via Ephrin receptors is impaired in the intellectual disability syndrome BFLS","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"Gene Expression Omnibus (GEO GSE247838).","explanation":"The publication directly identifies GSE247838 as the repository accession."}],"notes":["GSE153164 and BrainSpan are reused developmental atlases rather than BFLS-generated datasets and are not represented as disease datasets here."],"contexts":[{"id":"disorder:Borjeson-Forssman-Lehmann_syndrome","name":"Borjeson-Forssman-Lehmann syndrome","kind":"Disorder","source_path":"kb/disorders/Borjeson-Forssman-Lehmann_syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Borjeson-Forssman-Lehmann_syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Borjeson-Forssman-Lehmann_syndrome.html#dataset-geo-gse247838"}],"context_names":["Borjeson-Forssman-Lehmann syndrome"],"disease_names":["Borjeson-Forssman-Lehmann syndrome"],"disease_name":"Borjeson-Forssman-Lehmann syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Borjeson-Forssman-Lehmann_syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Borjeson-Forssman-Lehmann_syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Borjeson-Forssman-Lehmann_syndrome.html#dataset-geo-gse247838"]},{"id":"dataset:geo:gse249131","accession":"geo:GSE249131","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE249131","title":"Single-cell RNA sequencing of blood cells from patients with VEXAS syndrome.","alternate_titles":[],"description":"We performed single cell RNA sequencing, and VDJ sequencing of TCR and BCR of peripheral blood samples (Peripheral Blood Mononuclear Cells[PBMCs]) from 9 patients with VEXAS to understand disease pathogenesis.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA 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Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:VEXAS_Syndrome","name":"VEXAS Syndrome","kind":"Disorder","source_path":"kb/disorders/VEXAS_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/VEXAS_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/VEXAS_Syndrome.html#dataset-geo-gse249131"}],"context_names":["VEXAS Syndrome"],"disease_names":["VEXAS Syndrome"],"disease_name":"VEXAS Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/VEXAS_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/VEXAS_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/VEXAS_Syndrome.html#dataset-geo-gse249131"]},{"id":"dataset:geo:gse250051","accession":"geo:GSE250051","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE250051","title":"Gene expression profiling of brain tissue from neuronopathic Gaucher disease mouse model of PG9VN, PG9V and wild type mice","alternate_titles":[],"description":"To understand the intrinsic link between PGRN and Gba D409V mutation dosage in regulating lysosomal function and disease pathogenesis, we generated nGD model of GbaD409V/D409V and loss of PGRN (Grn-/-), termed PG9V that displayed typical neuronopathic GD (nGD). With decreasing the dose of Gba D409V, i.e., D409V/Null, in Grn KO mice (Grn-/-;GbaD409V/Null, PG9VN) led to much earlier onset and more severe neurodegenerative nGD than PG9V mice.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[9],"sample_count":9,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39101473"],"publication_contexts":[{"context_id":"disorder:Gaucher_Disease","publication":"PMID:39101473"}],"publication":"PMID:39101473","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39101473","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Gaucher Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Gaucher_Disease","name":"Gaucher Disease","kind":"Disorder","source_path":"kb/disorders/Gaucher_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Gaucher_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Gaucher_Disease.html#dataset-geo-gse250051"}],"context_names":["Gaucher Disease"],"disease_names":["Gaucher Disease"],"disease_name":"Gaucher Disease","same_context_model_ids":["model:kb/disorders/Gaucher_Disease.yaml:CBE-treated murine macrophage conditioned-medium model","model:kb/disorders/Gaucher_Disease.yaml:GD1 patient bone marrow stromal cells"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Gaucher_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Gaucher_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Gaucher_Disease.html#dataset-geo-gse250051"]},{"id":"dataset:geo:gse250295","accession":"geo:GSE250295","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE250295","title":"G-quadruplexes within the SVA retrotransposon modulate TAF1 gene expression in X-linked Dystonia Parkinsonism","alternate_titles":[],"description":"GEO SuperSeries combining RNA-seq and G4 chromatin-occupancy profiling in human XDP cellular models used to test the G-quadruplex mechanism.","alternate_descriptions":[],"data_types":["MULTI_OMICS"],"data_type_labels":["Multi Omics"],"data_type_label":"Multi Omics","organisms":[{"id":"NCBITaxon:9606","label":"Homo 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Dystonia-Parkinsonism","kind":"Disorder","source_path":"kb/disorders/X-linked_Dystonia-Parkinsonism.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/X-linked_Dystonia-Parkinsonism.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/X-linked_Dystonia-Parkinsonism.html#dataset-geo-gse250295"}],"context_names":["X-linked Dystonia-Parkinsonism"],"disease_names":["X-linked Dystonia-Parkinsonism"],"disease_name":"X-linked Dystonia-Parkinsonism","same_context_model_ids":["model:kb/disorders/X-linked_Dystonia-Parkinsonism.yaml:Human neural-progenitor SVA mini-heterochromatin model","model:kb/disorders/X-linked_Dystonia-Parkinsonism.yaml:Isogenic XDP striatal organoid repeat-RNA model","model:kb/disorders/X-linked_Dystonia-Parkinsonism.yaml:Patient-derived fibroblast and neural-progenitor G-quadruplex model","model:kb/disorders/X-linked_Dystonia-Parkinsonism.yaml:XDP iPSC-derived neural stem cells and medium spiny neurons","model:kb/disorders/X-linked_Dystonia-Parkinsonism.yaml:XDP iPSC-derived neuronal lineages with CRISPR SVA excision"],"candidate_model_ids":["model:kb/disorders/X-linked_Dystonia-Parkinsonism.yaml:Patient-derived fibroblast and neural-progenitor G-quadruplex model"],"association_basis":"Same publication as a NAM (candidate)","nam_disease_context":"Same publication as a NAM (candidate)","source_paths":["kb/disorders/X-linked_Dystonia-Parkinsonism.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/X-linked_Dystonia-Parkinsonism.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/X-linked_Dystonia-Parkinsonism.html#dataset-geo-gse250295"]},{"id":"dataset:geo:gse251755","accession":"geo:GSE251755","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE251755","title":"Differential gene expression profile of germline STK11 deletion in patient derived fibroblasts","alternate_titles":[],"description":"Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disorder hallmarked by mucocutaneous melanocytic macules and gastrointestinal hamartomatous polyposis associated with germline/somatic pathogenic variants in the tumor suppressor STK11. PJS is clinically heterogeneous, however, the relationship between clinical phenotype and genotype remains elusive. Here, we report a family with variable severity PJS who harbor a heterozygous STK11 whole gene deletion combined with heterozygous variants in PMS2 and TP53AIP1 that segregate with disease severity in the family.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40860288"],"publication_contexts":[{"context_id":"disorder:Peutz_Jeghers_Syndrome","publication":"PMID:40860288"}],"publication":"PMID:40860288","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40860288","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Peutz-Jeghers syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Peutz_Jeghers_Syndrome","name":"Peutz-Jeghers syndrome","kind":"Disorder","source_path":"kb/disorders/Peutz_Jeghers_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Peutz_Jeghers_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Peutz-Jeghers_syndrome.html#dataset-geo-gse251755"}],"context_names":["Peutz-Jeghers syndrome"],"disease_names":["Peutz-Jeghers syndrome"],"disease_name":"Peutz-Jeghers syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Peutz_Jeghers_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Peutz_Jeghers_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Peutz-Jeghers_syndrome.html#dataset-geo-gse251755"]},{"id":"dataset:geo:gse252400","accession":"geo:GSE252400","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE252400","title":"Epigenetic Modulation to perturb the SYNGAP1 Intellectual Disability (ID) that ameliorates synaptic and behavioural deficits","alternate_titles":[],"description":"Whole-hippocampal RNA sequencing across six arms - wild-type and Syngap1+/- mice each given saline, carrier nanosphere alone, or the nanosphere-conjugated p300/CBP acetyltransferase activator CSP-TTK21 - profiled after Morris water maze training. The design carries both the haploinsufficiency comparison and a pharmacological rescue arm, so it is usable for the SYNGAP1 loss-of-function transcriptome and for testing whether that transcriptome is reversible in the adult animal.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"house mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[18],"sample_count":18,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:11497","label":"SYNGAP1","display_label":"SYNGAP1","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/11497"}],"genes":["SYNGAP1"],"platforms":[],"platform":null,"publications":["PMID:39878322"],"publication_contexts":[{"context_id":"disorder:SYNGAP1-Related_Developmental_and_Epileptic_Encephalopathy","publication":"PMID:39878322"}],"publication":"PMID:39878322","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39878322","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Found by a targeted GEO DataSets search for SYNGAP1; accession and metadata verified against NCBI E-utilities on 2026-08-27. Title, sample count, and organism are GEO's own values. Model-organism data - the gene descriptor is the human HGNC record for the disease gene; the mouse orthologue is Syngap1. GEO lists no linked PMID on the series; the publication recorded here is the paper reporting this experiment, matched on the series summary and design. This is the only SYNGAP1 disease dataset in GEO as of 2026-08-27 - a search across all fields returns seven other series, none of which studies SYNGAP1 loss of function."],"contexts":[{"id":"disorder:SYNGAP1-Related_Developmental_and_Epileptic_Encephalopathy","name":"SYNGAP1-Related Developmental and Epileptic Encephalopathy","kind":"Disorder","source_path":"kb/disorders/SYNGAP1-Related_Developmental_and_Epileptic_Encephalopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/SYNGAP1-Related_Developmental_and_Epileptic_Encephalopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/SYNGAP1-Related_Developmental_and_Epileptic_Encephalopathy.html#dataset-geo-gse252400"}],"context_names":["SYNGAP1-Related Developmental and Epileptic Encephalopathy"],"disease_names":["SYNGAP1-Related Developmental and Epileptic Encephalopathy"],"disease_name":"SYNGAP1-Related Developmental and Epileptic Encephalopathy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/SYNGAP1-Related_Developmental_and_Epileptic_Encephalopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/SYNGAP1-Related_Developmental_and_Epileptic_Encephalopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/SYNGAP1-Related_Developmental_and_Epileptic_Encephalopathy.html#dataset-geo-gse252400"]},{"id":"dataset:geo:gse253226","accession":"geo:GSE253226","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE253226","title":"PKP2 Gene Therapy Improves Heart Function and Reduces Mortality in a Pkp2-deficient Mouse Model of Arrhythmogenic Right Ventricular Cardiomyopathy","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[112],"sample_count":112,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:38499690"],"publication_contexts":[{"context_id":"disorder:Arrhythmogenic_Right_Ventricular_Cardiomyopathy","publication":"PMID:38499690"},{"context_id":"disorder:PKP2_Cardiomyopathy","publication":"PMID:38499690"}],"publication":"PMID:38499690","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38499690","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for arrhythmogenic right ventricular cardiomyopathy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.","Identified by GEO DataSets index search for PKP2 Cardiomyopathy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Arrhythmogenic_Right_Ventricular_Cardiomyopathy","name":"arrhythmogenic right ventricular cardiomyopathy","kind":"Disorder","source_path":"kb/disorders/Arrhythmogenic_Right_Ventricular_Cardiomyopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Arrhythmogenic_Right_Ventricular_Cardiomyopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/arrhythmogenic_right_ventricular_cardiomyopathy.html#dataset-geo-gse253226"},{"id":"disorder:PKP2_Cardiomyopathy","name":"PKP2_Cardiomyopathy","kind":"Disorder","source_path":"kb/disorders/PKP2_Cardiomyopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/PKP2_Cardiomyopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/PKP2_Cardiomyopathy.html#dataset-geo-gse253226"}],"context_names":["arrhythmogenic right ventricular cardiomyopathy","PKP2_Cardiomyopathy"],"disease_names":["arrhythmogenic right ventricular cardiomyopathy","PKP2_Cardiomyopathy"],"disease_name":"arrhythmogenic right ventricular cardiomyopathy","same_context_model_ids":["model:kb/disorders/Arrhythmogenic_Right_Ventricular_Cardiomyopathy.yaml:Heterozygous plakoglobin-deficient (plakoglobin+/-) mouse"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Arrhythmogenic_Right_Ventricular_Cardiomyopathy.yaml","kb/disorders/PKP2_Cardiomyopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Arrhythmogenic_Right_Ventricular_Cardiomyopathy.yaml","https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/PKP2_Cardiomyopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/arrhythmogenic_right_ventricular_cardiomyopathy.html#dataset-geo-gse253226","https://dismech.monarchinitiative.org/pages/disorders/PKP2_Cardiomyopathy.html#dataset-geo-gse253226"]},{"id":"dataset:geo:gse253344","accession":"geo:GSE253344","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE253344","title":"Potential off-targets investigation of a lead antisense oligonucleotides targeting ABCA4 c.768G>T in retinal organoids","alternate_titles":[],"description":"Human retinal organoid bulk RNA-seq dataset generated during preclinical antisense-oligonucleotide development for the recurrent ABCA4 c.768G>T splice defect in STGD1.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0000966","label":"retina","display_label":"retinal organoid","url":"http://purl.obolibrary.org/obo/UBERON_0000966"}],"sample_type_labels":["retina"],"sample_counts":[8],"sample_count":8,"conditions":["Stargardt disease","antisense oligonucleotide treatment","splice-defect rescue experiment"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39838063"],"publication_contexts":[{"context_id":"disorder:Stargardt_Disease","publication":"PMID:39838063"}],"publication":"PMID:39838063","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39838063","publication_status":"Publication recorded","findings":[{"statement":"Transcriptomic profiling of treated retinal organoids supports splicing rescue of the ABCA4 c.768G>T defect without major off-target safety signals.","evidence":[{"reference":"PMID:39838063","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39838063","reference_title":"Preclinical assessment of splicing modulation therapy for ABCA4 variant c.768G>T in Stargardt disease.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Testing of these AONs in patient-derived photoreceptor precursor cells and retinal organoids allow the selection of a lead candidate AON (A7 21-mer) that rescues on average 52% and 50% expression of wild-type ABCA4 transcript and protein, respectively.","explanation":"This demonstrates that the dataset captures a therapeutically meaningful rescue signal in disease-relevant retinal models."},{"reference":"PMID:39838063","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39838063","reference_title":"Preclinical assessment of splicing modulation therapy for ABCA4 variant c.768G>T in Stargardt disease.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"No major safety concerns regarding off-targets, immunostimulation and toxicity are observed in transcriptomics analysis, cytokine stimulation assays in human primary immune cells, and cytotoxicity assays.","explanation":"This supports the dataset's usefulness for evaluating transcriptome-level off-target and safety effects."}]}],"findings_text":["Transcriptomic profiling of treated retinal organoids supports splicing rescue of the ABCA4 c.768G>T defect without major off-target safety signals."],"evidence":[{"reference":"PMID:39838063","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39838063","reference_title":"Preclinical assessment of splicing modulation therapy for ABCA4 variant c.768G>T in Stargardt disease.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Testing of these AONs in patient-derived photoreceptor precursor cells and retinal organoids allow the selection of a lead candidate AON (A7 21-mer) that rescues on average 52% and 50% expression of wild-type ABCA4 transcript and protein, respectively.","explanation":"This supports the GEO series as a Stargardt-relevant therapeutic perturbation dataset in disease-model retinal tissue."},{"reference":"PMID:39838063","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39838063","reference_title":"Preclinical assessment of splicing modulation therapy for ABCA4 variant c.768G>T in Stargardt disease.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"No major safety concerns regarding off-targets, immunostimulation and toxicity are observed in transcriptomics analysis, cytokine stimulation assays in human primary immune cells, and cytotoxicity assays.","explanation":"This supports the dataset's usefulness for evaluating transcriptome-level off-target and safety effects."}],"notes":[],"contexts":[{"id":"disorder:Stargardt_Disease","name":"Stargardt Disease","kind":"Disorder","source_path":"kb/disorders/Stargardt_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Stargardt_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Stargardt_Disease.html#dataset-geo-gse253344"}],"context_names":["Stargardt Disease"],"disease_names":["Stargardt Disease"],"disease_name":"Stargardt Disease","same_context_model_ids":["model:kb/disorders/Stargardt_Disease.yaml:Patient-derived retinal organoid model","model:kb/disorders/Stargardt_Disease.yaml:STGD1 iPSC-derived RPE disease-in-a-dish model"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Stargardt_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Stargardt_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Stargardt_Disease.html#dataset-geo-gse253344"]},{"id":"dataset:geo:gse253680","accession":"geo:GSE253680","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE253680","title":"Transcriptomic analysis of fetal epaxial muscle fibers from wildtype and dyW/dyW mice at embryonic day 17.5","alternate_titles":[],"description":"Fetal muscle-fibre transcriptomes from dyW/dyW and wild-type mice at embryonic day 17.5, the point at which disease onset has been placed in this model. It is the dataset that speaks most directly to the entry's claim that the pathology begins before birth rather than accumulating after it.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"house mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[7],"sample_count":7,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:6482","label":"LAMA2","display_label":"LAMA2","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/6482"}],"genes":["LAMA2"],"platforms":[],"platform":null,"publications":["PMID:39379105"],"publication_contexts":[{"context_id":"disorder:Congenital_Merosin-deficient_Muscular_Dystrophy_1A","publication":"PMID:39379105"}],"publication":"PMID:39379105","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39379105","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE253680","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE253680","reference_title":"Transcriptomic analysis of fetal epaxial muscle fibers from wildtype and dyW/dyW mice at embryonic day 17.5","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"However, it is not yet known what mechanisms are faulty, right at disease onset, which in the mouse model of LAMA2-CMD dyW/dyW has been previously established to occur between embryonic days (E) 17.5 and E18.5.","explanation":"The repository summary dates disease onset in this model to late gestation, which is what makes the dataset relevant to the prenatal-onset claim in the neonatal progression phase."}],"notes":[],"contexts":[{"id":"disorder:Congenital_Merosin-deficient_Muscular_Dystrophy_1A","name":"Congenital Merosin-deficient Muscular Dystrophy 1A","kind":"Disorder","source_path":"kb/disorders/Congenital_Merosin-deficient_Muscular_Dystrophy_1A.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Congenital_Merosin-deficient_Muscular_Dystrophy_1A.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Congenital_Merosin-deficient_Muscular_Dystrophy_1A.html#dataset-geo-gse253680"}],"context_names":["Congenital Merosin-deficient Muscular Dystrophy 1A"],"disease_names":["Congenital Merosin-deficient Muscular Dystrophy 1A"],"disease_name":"Congenital Merosin-deficient Muscular Dystrophy 1A","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Congenital_Merosin-deficient_Muscular_Dystrophy_1A.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Congenital_Merosin-deficient_Muscular_Dystrophy_1A.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Congenital_Merosin-deficient_Muscular_Dystrophy_1A.html#dataset-geo-gse253680"]},{"id":"dataset:geo:gse253700","accession":"geo:GSE253700","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE253700","title":"Early Host Immune Responses in Human Gallbladder to Salmonella Typhi Strains from Patients with Acute and Chronic Infections","alternate_titles":[],"description":"Microarray profiles of human organoid-derived polarized gallbladder monolayers infected with S. Typhi strains derived from acutely and chronically infected patients.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[35],"sample_count":35,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:38533492"],"publication_contexts":[{"context_id":"disorder:Typhoid_Fever","publication":"PMID:38533492"}],"publication":"PMID:38533492","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38533492","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Typhoid Fever; accession and metadata verified against NCBI E-utilities on 2026-09-25. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Typhoid_Fever","name":"Typhoid Fever","kind":"Disorder","source_path":"kb/disorders/Typhoid_Fever.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Typhoid_Fever.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Typhoid_Fever.html#dataset-geo-gse253700"}],"context_names":["Typhoid Fever"],"disease_names":["Typhoid Fever"],"disease_name":"Typhoid Fever","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Typhoid_Fever.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Typhoid_Fever.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Typhoid_Fever.html#dataset-geo-gse253700"]},{"id":"dataset:geo:gse254003","accession":"geo:GSE254003","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE254003","title":"A deep intronic splice-altering AIRE variant causes APECED syndrome through antisense oligonucleotide-targetable pseudoexon inclusion","alternate_titles":[],"description":"Bulk RNA-sequencing of human TEC4D6 thymic epithelial cells transfected with wild-type AIRE, pseudoexon-containing mutant AIRE, or GFP control. This is a mechanistic cell-line dataset rather than patient tissue and should not be used to estimate clinical expression frequencies.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"CL:0002293","label":"epithelial cell of thymus","display_label":"thymic epithelial cell","url":"http://purl.obolibrary.org/obo/CL_0002293"}],"sample_type_labels":["epithelial cell of thymus"],"sample_counts":[12],"sample_count":12,"conditions":["Wild-type AIRE transfection","Deep-intronic-variant AIRE transfection","GFP control transfection"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39292801"],"publication_contexts":[{"context_id":"disorder:Autoimmune_Polyendocrinopathy","publication":"PMID:39292801"}],"publication":"PMID:39292801","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39292801","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:39292801","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39292801","reference_title":"A deep intronic splice-altering AIRE variant causes APECED syndrome through antisense oligonucleotide-targetable pseudoexon inclusion.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Through protein modeling and transcriptomic analyses of AIRE-transfected human embryonic kidney 293 and thymic epithelial cell 4D6 cells, we showed that this variant alters the carboxyl terminus of the AIRE protein, abrogating its function.","explanation":"The publication identifies the cell systems and transcriptomic purpose represented by the GEO series."}],"notes":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE254003"],"contexts":[{"id":"disorder:Autoimmune_Polyendocrinopathy","name":"Autoimmune Polyendocrinopathy","kind":"Disorder","source_path":"kb/disorders/Autoimmune_Polyendocrinopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autoimmune_Polyendocrinopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autoimmune_Polyendocrinopathy.html#dataset-geo-gse254003"}],"context_names":["Autoimmune Polyendocrinopathy"],"disease_names":["Autoimmune Polyendocrinopathy"],"disease_name":"Autoimmune Polyendocrinopathy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Autoimmune_Polyendocrinopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autoimmune_Polyendocrinopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Autoimmune_Polyendocrinopathy.html#dataset-geo-gse254003"]},{"id":"dataset:geo:gse254100","accession":"geo:GSE254100","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE254100","title":"Cellular responses in the airway ciliary microenvironment from mouse models of primary ciliary dyskinesia with central pair apparatus defects","alternate_titles":[],"description":"Public mouse tracheal scRNA-seq with four GEO sample records: wild type and Cfap221/Pcdp1 nm1054, Spef2 bgh and Cfap54 gene-trap mutant preparations on the 129S6/SvEvTac background. Published cell-type-specific differential expression includes shared and distinct responses across genotypes. Human HGNC bindings identify the orthologous disease genes; the samples are mouse, not human. No raw-data reanalysis was performed in this curation.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"house mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:33720","label":"CFAP221","display_label":"CFAP221","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/33720"},{"id":"hgnc:26456","label":"CFAP54","display_label":"CFAP54","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/26456"},{"id":"hgnc:26293","label":"SPEF2","display_label":"SPEF2","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/26293"}],"genes":["CFAP221","CFAP54","SPEF2"],"platforms":[],"platform":null,"publications":["PMID:39558053"],"publication_contexts":[{"context_id":"disorder:Primary_Ciliary_Dyskinesia","publication":"PMID:39558053"}],"publication":"PMID:39558053","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39558053","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:39558053","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39558053","reference_title":"Airway ciliary microenvironment responses in mice with primary ciliary dyskinesia and central pair apparatus defects.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"we have used single-cell RNA sequencing to investigate responses in tracheal epithelial cells from mice with mutations in CPA genes","explanation":"Single-cell transcriptomic dataset of tracheal epithelium from central-pair-apparatus PCD mouse models (Cfap221, Cfap54, Spef2)."}],"notes":[],"contexts":[{"id":"disorder:Primary_Ciliary_Dyskinesia","name":"Primary_Ciliary_Dyskinesia","kind":"Disorder","source_path":"kb/disorders/Primary_Ciliary_Dyskinesia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Primary_Ciliary_Dyskinesia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Ciliary_Dyskinesia.html#dataset-geo-gse254100"}],"context_names":["Primary_Ciliary_Dyskinesia"],"disease_names":["Primary_Ciliary_Dyskinesia"],"disease_name":"Primary_Ciliary_Dyskinesia","same_context_model_ids":["model:kb/disorders/Primary_Ciliary_Dyskinesia.yaml:BCi-NS1.1 dyskinetic airway epithelial cell line","model:kb/disorders/Primary_Ciliary_Dyskinesia.yaml:BMI1-expanded DNAH5 patient airway epithelial cell model","model:kb/disorders/Primary_Ciliary_Dyskinesia.yaml:C1d-defective patient airway transport 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as a NAM","source_paths":["kb/disorders/Primary_Ciliary_Dyskinesia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Primary_Ciliary_Dyskinesia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Primary_Ciliary_Dyskinesia.html#dataset-geo-gse254100"]},{"id":"dataset:geo:gse254205","accession":"geo:GSE254205","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE254205","title":"APOE4/4 is linked to damaging lipid droplets in Alzheimer's microglia","alternate_titles":[],"description":"Single-nucleus RNA-seq of human Alzheimer brain stratified by APOE genotype, defining the ACSL1-positive lipid-droplet microglial state that is most abundant in APOE4/4 carriers.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA 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Because the donors are APOE-genotyped, the same nuclei also bear on whether the glial lipid phenotype is microglia-specific or shared with the oligodendrocyte lineage. Accession resolved against the GEO API with `just verify-datasets`."],"contexts":[{"id":"disorder:Alzheimer_Disease","name":"Alzheimer Disease","kind":"Disorder","source_path":"kb/disorders/Alzheimer_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alzheimer_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Alzheimer_Disease.html#dataset-geo-gse254205"}],"context_names":["Alzheimer Disease"],"disease_names":["Alzheimer Disease"],"disease_name":"Alzheimer Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association 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vitro","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Differentiation was monitored over 31 days through the detection of lineage-specific marker expression by qRT-PCR, immunofluorescence, and transcriptomics analysis.","explanation":"This GEO dataset contains transcriptomic analysis of JS iPSC differentiation."}],"notes":[],"contexts":[{"id":"disorder:Joubert_syndrome","name":"Joubert syndrome","kind":"Disorder","source_path":"kb/disorders/Joubert_syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Joubert_syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Joubert_syndrome.html#dataset-geo-gse254556"}],"context_names":["Joubert syndrome"],"disease_names":["Joubert syndrome"],"disease_name":"Joubert syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association 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Triaged as directly on-disease from the series title."],"contexts":[{"id":"disorder:Bone_Giant_Cell_Tumor","name":"Bone Giant Cell Tumor","kind":"Disorder","source_path":"kb/disorders/Bone_Giant_Cell_Tumor.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bone_Giant_Cell_Tumor.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Bone_Giant_Cell_Tumor.html#dataset-geo-gse254672"}],"context_names":["Bone Giant Cell Tumor"],"disease_names":["Bone Giant Cell Tumor"],"disease_name":"Bone Giant Cell Tumor","same_context_model_ids":["model:kb/disorders/Bone_Giant_Cell_Tumor.yaml:CRISPR-Cas9 H3.3 G34W-edited GCTB tumor-derived cells","model:kb/disorders/Bone_Giant_Cell_Tumor.yaml:Monocyte osteoclastogenesis co-culture with GCTB stromal cells","model:kb/disorders/Bone_Giant_Cell_Tumor.yaml:Patient-derived GCTB stromal cell culture"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Bone_Giant_Cell_Tumor.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bone_Giant_Cell_Tumor.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Bone_Giant_Cell_Tumor.html#dataset-geo-gse254672"]},{"id":"dataset:geo:gse254959","accession":"geo:GSE254959","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE254959","title":"Efficacy of melflufen in relapsed and refractory multiple myeloma patients with mutated or deleted TP53","alternate_titles":[],"description":"Despite the development of several new treatments for multiple myeloma (MM) clinical challenges remain for patients with relapsed/refractory disease. This is especially so for the high-risk subgroup of patients with del(17p) who have poor response and significantly shorter survival compared to patients without this aberration. Here, we report the clinical efficacy of melphalan flufenamide (melflufen) in patients with del(17p) from the OCEAN randomized, open label, head-to-head, phase III clinical trial. In the del(17p) subgroup, melflufen plus dexamethasone treatment resulted in favorable progression free survival compared to the pomalidomide plus dexamethasone arm.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[36],"sample_count":36,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41437395"],"publication_contexts":[{"context_id":"disorder:Multiple_Myeloma","publication":"PMID:41437395"}],"publication":"PMID:41437395","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41437395","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Multiple Myeloma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Multiple_Myeloma","name":"Multiple Myeloma","kind":"Disorder","source_path":"kb/disorders/Multiple_Myeloma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Multiple_Myeloma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Multiple_Myeloma.html#dataset-geo-gse254959"}],"context_names":["Multiple Myeloma"],"disease_names":["Multiple Myeloma"],"disease_name":"Multiple Myeloma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Multiple_Myeloma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Multiple_Myeloma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Multiple_Myeloma.html#dataset-geo-gse254959"]},{"id":"dataset:geo:gse254972","accession":"geo:GSE254972","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE254972","title":"JPF promotes repair of early nontraumatic osteonecrosis of the femoral head by inhibiting NAMPT/STK11/HMGCR/ACAT1 signal axis-mediated lipid production","alternate_titles":[],"description":"Jianpi Huogu Formula (JPF) has achieved good curative effects in nontraumatic osteonecrosis of the femoral head (NONFH) in clinical practice. However, its underlying pharmacological mechanisms remain unclear. Herein, chemical constituents of JPF were systematically identified by UPLC-Q-TOF-MS, and the putative targets were predicted using TCMIP v2.0 platform. Then, the transcriptomic profiling based on clinical cohorts were carried out to identify the early NONFH-related genes and JPF effective targets. Following network-based calculation and functional enrichment analysis, JPF candidate targets against early NONFH were screened and further validated by a series of in vivo experiments.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[8],"sample_count":8,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Osteonecrosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Osteonecrosis","name":"Osteonecrosis","kind":"Disorder","source_path":"kb/disorders/Osteonecrosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Osteonecrosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Osteonecrosis.html#dataset-geo-gse254972"}],"context_names":["Osteonecrosis"],"disease_names":["Osteonecrosis"],"disease_name":"Osteonecrosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Osteonecrosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Osteonecrosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Osteonecrosis.html#dataset-geo-gse254972"]},{"id":"dataset:geo:gse255685","accession":"geo:GSE255685","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE255685","title":"Age-related transcriptomic differences in peripheral blood of adolescents with major depressive disorder","alternate_titles":[],"description":"In this study, we collected peripheral blood samples of a typical large population, including MDD cases and healthy controls from children and adolescents, and aimed to apply RNA-seq sequencing to comprehensively analyze the transcriptomic characteristics in adolescent depression patients. In comparison to healthy patients, we discovered that several immune response-associated genes were dysregulated in MDD patients, with the majority of these differential genes strongly correlated with the HAMD-17 and HAMA scores.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[279],"sample_count":279,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41740874"],"publication_contexts":[{"context_id":"disorder:Major_Depressive_Disorder","publication":"PMID:41740874"}],"publication":"PMID:41740874","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41740874","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Major Depressive Disorder (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Major_Depressive_Disorder","name":"Major Depressive Disorder","kind":"Disorder","source_path":"kb/disorders/Major_Depressive_Disorder.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Major_Depressive_Disorder.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Major_Depressive_Disorder.html#dataset-geo-gse255685"}],"context_names":["Major Depressive Disorder"],"disease_names":["Major Depressive Disorder"],"disease_name":"Major Depressive Disorder","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Major_Depressive_Disorder.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Major_Depressive_Disorder.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Major_Depressive_Disorder.html#dataset-geo-gse255685"]},{"id":"dataset:geo:gse255796","accession":"geo:GSE255796","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE255796","title":"A Cell Type-Specific Approach to Elucidate the Role of miR-96 in Inner Ear Hair Cells","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:31648","label":"MIR96","display_label":"MIR96","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/31648"}],"genes":["MIR96"],"platforms":[],"platform":null,"publications":["PMID:38826689"],"publication_contexts":[{"context_id":"disorder:Autosomal_Dominant_Nonsyndromic_Hearing_Loss_50","publication":"PMID:38826689"}],"publication":"PMID:38826689","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38826689","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:38826689","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38826689","reference_title":"A cell type-specific approach to elucidate the role of miR-96 in inner ear hair cells.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"An important limitation of this study is the inclusion of both cochlear and vestibular HCs to generate the RNA for bulk sequencing.","explanation":"Defines the sampled cell population."}],"notes":["P1 bulk RNA-seq of FACS-isolated hair cells from cochlear and vestibular organs combined, with three mice per genotype (wild type, heterozygous and homozygous diminuendo). This supports cell-type enrichment, not cochlear-only or single-cell resolution. The publication reports a broad maturation-gene signature; an allele-specific Clic5 conclusion would require inspection of the gene-level data."],"contexts":[{"id":"disorder:Autosomal_Dominant_Nonsyndromic_Hearing_Loss_50","name":"Autosomal Dominant Nonsyndromic Hearing Loss 50","kind":"Disorder","source_path":"kb/disorders/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_50.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_50.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_50.html#dataset-geo-gse255796"}],"context_names":["Autosomal Dominant Nonsyndromic Hearing Loss 50"],"disease_names":["Autosomal Dominant Nonsyndromic Hearing Loss 50"],"disease_name":"Autosomal Dominant Nonsyndromic Hearing Loss 50","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_50.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_50.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_50.html#dataset-geo-gse255796"]},{"id":"dataset:geo:gse255914","accession":"geo:GSE255914","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE255914","title":"Drosha loss drives pineoblastoma by upregulating Ccnd2","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[64],"sample_count":64,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40240142"],"publication_contexts":[{"context_id":"disorder:Pineoblastoma","publication":"PMID:40240142"}],"publication":"PMID:40240142","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40240142","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Pineoblastoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Pineoblastoma","name":"Pineoblastoma","kind":"Disorder","source_path":"kb/disorders/Pineoblastoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pineoblastoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pineoblastoma.html#dataset-geo-gse255914"}],"context_names":["Pineoblastoma"],"disease_names":["Pineoblastoma"],"disease_name":"Pineoblastoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Pineoblastoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pineoblastoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Pineoblastoma.html#dataset-geo-gse255914"]},{"id":"dataset:geo:gse255946","accession":"geo:GSE255946","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE255946","title":"Notum Regulates the Cusp and Root Patterns in Mouse Molar","alternate_titles":[],"description":"Bulk RNA-seq of Notum-deficient mouse molar tooth germs to study Wnt-feedback regulation of cusp and root patterning with root fusion phenotypes.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[{"id":"UBERON:0008281","label":"tooth bud","display_label":"maxillary and mandibular molar tooth germs","url":"http://purl.obolibrary.org/obo/UBERON_0008281"}],"sample_type_labels":["tooth bud"],"sample_counts":[8],"sample_count":8,"conditions":["Notum knockout","wild-type control"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["GPL24247"],"platform":"GPL24247","publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE255946","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE255946","reference_title":"Notum Regulates the Cusp and Root Patterns in Mouse Molar","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"Notum-deficient mice exhibited enlarged secondary EKs, resulting in broader cusp tips, altered cusp patterns, and reduced concavity in crown outline.","explanation":"Supports a root/crown patterning model relevant to developmental mechanisms that overlap taurodont root morphology."}],"notes":[],"contexts":[{"id":"disorder:Taurodontism","name":"Taurodontism","kind":"Disorder","source_path":"kb/disorders/Taurodontism.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Taurodontism.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Taurodontism.html#dataset-geo-gse255946"}],"context_names":["Taurodontism"],"disease_names":["Taurodontism"],"disease_name":"Taurodontism","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Taurodontism.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Taurodontism.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Taurodontism.html#dataset-geo-gse255946"]},{"id":"dataset:geo:gse256075","accession":"geo:GSE256075","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE256075","title":"Structural variant allelic heterogeneity in MECP2 Duplication Syndrome provides insight into clinical severity and variability of disease expression","alternate_titles":[],"description":"MECP2 Duplication Syndrome, also known as X-linked intellectual developmental disorder Lubs type (MRXSL; MIM: 300260), is a neurodevelopmental disorder caused by copy number gains spanning MECP2. Despite varying genomic rearrangement structures, including duplications and triplications, and a wide range of duplication sizes, no clear correlation exists between DNA rearrangement and clinical features.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[73],"sample_count":73,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39696717"],"publication_contexts":[{"context_id":"disorder:MECP2_Duplication_Syndrome","publication":"PMID:39696717"}],"publication":"PMID:39696717","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39696717","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for MECP2 Duplication Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:MECP2_Duplication_Syndrome","name":"MECP2 Duplication Syndrome","kind":"Disorder","source_path":"kb/disorders/MECP2_Duplication_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MECP2_Duplication_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/MECP2_Duplication_Syndrome.html#dataset-geo-gse256075"}],"context_names":["MECP2 Duplication Syndrome"],"disease_names":["MECP2 Duplication Syndrome"],"disease_name":"MECP2 Duplication Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/MECP2_Duplication_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MECP2_Duplication_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/MECP2_Duplication_Syndrome.html#dataset-geo-gse256075"]},{"id":"dataset:geo:gse256142","accession":"geo:GSE256142","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE256142","title":"Variability vs. phenotype: Multimodal analysis of Dravet syndrome brain organoids powered by deep learning","alternate_titles":[],"description":"Dravet Syndrome (DS) is a developmental epileptic encephalopathy (DEE) driven by pathogenic variants in SCN1A gene. Brain organoids (BO) have emerged as reliable models for neurodevelopmental genetic disorders, reproducing human brain developmental milestones and rising as a promising drug testing tool. Here, we determined the underlaying molecular DS pathophysiology affecting neuronal connectivity, revealing an early onset excitatory-inhibitory imbalance in maturing DS organoids circuitry. However, neuronal circuitry modeling in BO remains hampered by the notorious inter- and intra-organoid variability.","alternate_descriptions":["Dravet Syndrome (DS) is a developmental epileptic encephalopathy (DEE) driven by pathogenic variants in SCN1A gene. Brain organoids (BO) have emerged as reliable models for neurodevelopmental genetic disorders, reproducing human brain developmental milestones and rising as a promising drug testing tool. Here, we determined the underlying molecular DS pathophysiology affecting neuronal connectivity, revealing an early onset excitatory-inhibitory imbalance in maturing DS organoids circuitry. However, neuronal circuitry modeling in BO remains hampered by the notorious inter- and intra-organoid variability."],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[18],"sample_count":18,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41323276"],"publication_contexts":[{"context_id":"disorder:Dravet_syndrome","publication":"PMID:41323276"},{"context_id":"disorder:Genetic_Developmental_and_Epileptic_Encephalopathy","publication":"PMID:41323276"}],"publication":"PMID:41323276","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41323276","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Dravet syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.","Identified by GEO DataSets index search for Genetic Developmental and Epileptic Encephalopathy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Dravet_syndrome","name":"Dravet_syndrome","kind":"Disorder","source_path":"kb/disorders/Dravet_syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dravet_syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Dravet_syndrome.html#dataset-geo-gse256142"},{"id":"disorder:Genetic_Developmental_and_Epileptic_Encephalopathy","name":"Genetic Developmental and Epileptic Encephalopathy","kind":"Disorder","source_path":"kb/disorders/Genetic_Developmental_and_Epileptic_Encephalopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Genetic_Developmental_and_Epileptic_Encephalopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Genetic_Developmental_and_Epileptic_Encephalopathy.html#dataset-geo-gse256142"}],"context_names":["Dravet_syndrome","Genetic Developmental and Epileptic Encephalopathy"],"disease_names":["Dravet_syndrome","Genetic Developmental and Epileptic Encephalopathy"],"disease_name":"Dravet_syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Dravet_syndrome.yaml","kb/disorders/Genetic_Developmental_and_Epileptic_Encephalopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dravet_syndrome.yaml","https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Genetic_Developmental_and_Epileptic_Encephalopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Dravet_syndrome.html#dataset-geo-gse256142","https://dismech.monarchinitiative.org/pages/disorders/Genetic_Developmental_and_Epileptic_Encephalopathy.html#dataset-geo-gse256142"]},{"id":"dataset:geo:gse256539","accession":"geo:GSE256539","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE256539","title":"Digital Spatial Profiling identifies distinct molecular signatures of vascular lesions in Pulmonary Arterial Hypertension","alternate_titles":[],"description":"GeoMx digital spatial transcriptomics of individually microdissected IPAH vascular lesions - plexiform, obliterative, intima plus media hypertrophy and adventitia - from 11 IPAH lungs, compared with the intima plus media and adventitia of five control pulmonary arteries. This is the dataset behind the plexiform-lesion and medial-hypertrophy histopathology findings curated here.","alternate_descriptions":[],"data_types":["SPATIAL_TRANSCRIPTOMICS"],"data_type_labels":["Spatially resolved transcriptomics"],"data_type_label":"Spatially resolved transcriptomics","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[220],"sample_count":220,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:38568479"],"publication_contexts":[{"context_id":"disorder:Idiopathic_Pulmonary_Arterial_Hypertension","publication":"PMID:38568479"}],"publication":"PMID:38568479","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38568479","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Relevance triage: DIRECT. IPAH is named in the series title and the regions of interest are the IPAH lesions themselves. Accession resolved 2026-09-03."],"contexts":[{"id":"disorder:Idiopathic_Pulmonary_Arterial_Hypertension","name":"Idiopathic Pulmonary Arterial Hypertension","kind":"Disorder","source_path":"kb/disorders/Idiopathic_Pulmonary_Arterial_Hypertension.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Idiopathic_Pulmonary_Arterial_Hypertension.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Idiopathic_Pulmonary_Arterial_Hypertension.html#dataset-geo-gse256539"}],"context_names":["Idiopathic Pulmonary Arterial Hypertension"],"disease_names":["Idiopathic Pulmonary Arterial Hypertension"],"disease_name":"Idiopathic Pulmonary Arterial Hypertension","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Idiopathic_Pulmonary_Arterial_Hypertension.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Idiopathic_Pulmonary_Arterial_Hypertension.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Idiopathic_Pulmonary_Arterial_Hypertension.html#dataset-geo-gse256539"]},{"id":"dataset:geo:gse260949","accession":"geo:GSE260949","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE260949","title":"Analysis of a mouse germ cell tumor model establishes pluripotency-associated miRNAs as conserved serum biomarkers for germ cell cancer detection","alternate_titles":[],"description":"Malignant testicular germ cells tumors (TGCTs) are the most common solid cancers in young men. Current TGCT diagnostics include conventional serum protein markers, but these lack the sensitivity and specificity to serve as accurate markers across all TGCT subtypes. MicroRNAs (miRNAs) are small non-coding regulatory RNAs and informative biomarkers for several diseases. In humans, miRNAs of the miR-371-373 cluster are detectable in the serum of patients with malignant TGCTs and outperform existing serum protein markers for both initial diagnosis and subsequent disease monitoring.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39910147"],"publication_contexts":[{"context_id":"disorder:Mixed_Germ_Cell_Tumor","publication":"PMID:39910147"}],"publication":"PMID:39910147","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39910147","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Mixed Germ Cell Tumor (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Mixed_Germ_Cell_Tumor","name":"Mixed Germ Cell Tumor","kind":"Disorder","source_path":"kb/disorders/Mixed_Germ_Cell_Tumor.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mixed_Germ_Cell_Tumor.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Mixed_Germ_Cell_Tumor.html#dataset-geo-gse260949"}],"context_names":["Mixed Germ Cell Tumor"],"disease_names":["Mixed Germ Cell Tumor"],"disease_name":"Mixed Germ Cell Tumor","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Mixed_Germ_Cell_Tumor.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mixed_Germ_Cell_Tumor.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Mixed_Germ_Cell_Tumor.html#dataset-geo-gse260949"]},{"id":"dataset:geo:gse260988","accession":"geo:GSE260988","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE260988","title":"Coactivator-independent vitamin D receptor signaling impairs intestinal calcium transport in mice, leading to severe rickets, which is not prevented by a diet high in calcium, phosphate, and lactose.","alternate_titles":[],"description":"Bulk RNA sequencing of duodenum and kidney from 8-week-old female wild-type, Vdr-null, and systemic VdrΔAF2 mice maintained on a high-calcium, high-phosphate, high-lactose diet. Each tissue contributes six wild-type, four null, and four VdrΔAF2 samples, for 28 samples total.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[{"id":"UBERON:0002114","label":"duodenum","display_label":"duodenum","url":"http://purl.obolibrary.org/obo/UBERON_0002114"},{"id":"UBERON:0001225","label":"cortex of kidney","display_label":"kidney cortex","url":"http://purl.obolibrary.org/obo/UBERON_0001225"}],"sample_type_labels":["duodenum","cortex of kidney"],"sample_counts":[28],"sample_count":28,"conditions":["Vdr wild-type","Vdr knockout","systemic Vdr Delta-AF2","high-calcium, high-phosphate, high-lactose rescue diet"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["QuantSeq expression profiling on Illumina HiSeq 4000"],"platform":"QuantSeq expression profiling on Illumina HiSeq 4000","publications":["PMID:39164247"],"publication_contexts":[{"context_id":"disorder:Vitamin_D-Dependent_Rickets_Type_2A","publication":"PMID:39164247"}],"publication":"PMID:39164247","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39164247","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:39164247","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39164247","reference_title":"Coactivator-independent vitamin D receptor signaling causes severe rickets in mice, that is not prevented by a diet high in calcium, phosphate, and lactose.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"In addition, RNA-sequencing analysis of duodenum and kidney revealed a decreased expression of VDR target genes in systemic VdrΔAF2 mice, which was not observed in Vdr-/- mice.","explanation":"Confirms the tissues, sequencing modality, and mechanistic comparison represented by the dataset."}],"notes":["GEO metadata and accession were independently resolved with just verify-datasets on 2026-08-20."],"contexts":[{"id":"disorder:Vitamin_D-Dependent_Rickets_Type_2A","name":"Vitamin D-Dependent Rickets Type 2A","kind":"Disorder","source_path":"kb/disorders/Vitamin_D-Dependent_Rickets_Type_2A.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Vitamin_D-Dependent_Rickets_Type_2A.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Vitamin_D-Dependent_Rickets_Type_2A.html#dataset-geo-gse260988"}],"context_names":["Vitamin D-Dependent Rickets Type 2A"],"disease_names":["Vitamin D-Dependent Rickets Type 2A"],"disease_name":"Vitamin D-Dependent Rickets Type 2A","same_context_model_ids":["model:kb/disorders/Vitamin_D-Dependent_Rickets_Type_2A.yaml:Patient-Derived p.Arg30* VDR Dermal Fibroblasts"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Vitamin_D-Dependent_Rickets_Type_2A.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Vitamin_D-Dependent_Rickets_Type_2A.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Vitamin_D-Dependent_Rickets_Type_2A.html#dataset-geo-gse260988"]},{"id":"dataset:geo:gse261102","accession":"geo:GSE261102","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE261102","title":"Autologous transplantation of P63+ lung progenitor cells in patients with bronchiectasis: a randomized, single-blind, controlled trial","alternate_titles":[],"description":"Non-cystic fibrosis bronchiectasis is a severe respiratory disease characterized by progressive loss of lung function, resulting in high morbidity and even early mortality. Current treatments cannot repair progressive lung damage, which encouraged the exploration of stem and progenitor cell-based regenerative therapies. In current study, we found that the P63+ progenitor cells normally located in airway basal layer could appear in the alveolar spaces of bronchiectasis patients. We successfully cloned and expanded the progenitor cells from the airway brushing tissues of patients.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[7],"sample_count":7,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39566467"],"publication_contexts":[{"context_id":"disorder:Bronchiectasis","publication":"PMID:39566467"}],"publication":"PMID:39566467","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39566467","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Bronchiectasis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Bronchiectasis","name":"Bronchiectasis","kind":"Disorder","source_path":"kb/disorders/Bronchiectasis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bronchiectasis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Bronchiectasis.html#dataset-geo-gse261102"}],"context_names":["Bronchiectasis"],"disease_names":["Bronchiectasis"],"disease_name":"Bronchiectasis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Bronchiectasis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bronchiectasis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Bronchiectasis.html#dataset-geo-gse261102"]},{"id":"dataset:geo:gse261158","accession":"geo:GSE261158","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE261158","title":"Aberrant neurodevelopment in human iPS cell-derived models of Alexander disease.","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[10],"sample_count":10,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39308436"],"publication_contexts":[{"context_id":"disorder:Alexander_Disease","publication":"PMID:39308436"}],"publication":"PMID:39308436","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39308436","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Alexander Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Alexander_Disease","name":"Alexander Disease","kind":"Disorder","source_path":"kb/disorders/Alexander_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alexander_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Alexander_Disease.html#dataset-geo-gse261158"}],"context_names":["Alexander Disease"],"disease_names":["Alexander Disease"],"disease_name":"Alexander Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Alexander_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alexander_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Alexander_Disease.html#dataset-geo-gse261158"]},{"id":"dataset:geo:gse261358","accession":"geo:GSE261358","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE261358","title":"Transcriptomic signature and pro-osteoclastic secreted factors of abnormal bone marrow stromal cells in fibrous dysplasia (Human)","alternate_titles":[],"description":"Fibrous dysplasia (FD) is a mosaic skeletal disorder caused by somatic activating variants in GNAS, encoding for Gαs, which leads to excessive cAMP signaling in bone marrow stromal cells (BMSCs). Despite advancements in our understanding of FD pathophysiology, the effect of Gαs activation in the BMSC transcriptome remains unclear, as well as how this translates into their local influence in the lesional microenvironment. In this study, we analyzed changes induced by Gαs activation in BMSC transcriptome and performed a comprehensive analysis of their production of cytokines and other secreted factors.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39273006"],"publication_contexts":[{"context_id":"disorder:Fibrous_Dysplasia","publication":"PMID:39273006"}],"publication":"PMID:39273006","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39273006","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Fibrous Dysplasia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Fibrous_Dysplasia","name":"Fibrous Dysplasia","kind":"Disorder","source_path":"kb/disorders/Fibrous_Dysplasia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fibrous_Dysplasia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Fibrous_Dysplasia.html#dataset-geo-gse261358"}],"context_names":["Fibrous Dysplasia"],"disease_names":["Fibrous Dysplasia"],"disease_name":"Fibrous Dysplasia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Fibrous_Dysplasia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fibrous_Dysplasia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Fibrous_Dysplasia.html#dataset-geo-gse261358"]},{"id":"dataset:geo:gse261534","accession":"geo:GSE261534","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE261534","title":"BPDCN MYB Fusions Regulate Cell Cycle Genes, Impair Differentiation and Induce Myeloid-Dendritic Cell Leukemia [BPDCNCutRun]","alternate_titles":[],"description":"CUT&RUN chromatin profiling in BPDCN cells showing MYB fusion binding redirected onto G2/M cell-cycle loci.","alternate_descriptions":[],"data_types":["CHIP_SEQ"],"data_type_labels":["Chromatin immunoprecipitation sequencing"],"data_type_label":"Chromatin immunoprecipitation sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39499902"],"publication_contexts":[{"context_id":"disorder:Blastic_Plasmacytoid_Dendritic_Cell_Neoplasm","publication":"PMID:39499902"}],"publication":"PMID:39499902","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39499902","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["CUT&RUN data are represented under the closest available chromatin-profiling data type. The companion series GSE261411 profiles K562 rather than BPDCN material."],"contexts":[{"id":"disorder:Blastic_Plasmacytoid_Dendritic_Cell_Neoplasm","name":"Blastic Plasmacytoid Dendritic Cell Neoplasm","kind":"Disorder","source_path":"kb/disorders/Blastic_Plasmacytoid_Dendritic_Cell_Neoplasm.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Blastic_Plasmacytoid_Dendritic_Cell_Neoplasm.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Blastic_Plasmacytoid_Dendritic_Cell_Neoplasm.html#dataset-geo-gse261534"}],"context_names":["Blastic Plasmacytoid Dendritic Cell Neoplasm"],"disease_names":["Blastic Plasmacytoid Dendritic Cell Neoplasm"],"disease_name":"Blastic Plasmacytoid Dendritic Cell Neoplasm","same_context_model_ids":["model:kb/disorders/Blastic_Plasmacytoid_Dendritic_Cell_Neoplasm.yaml:CAL-1 and GEN2.2 BPDCN cell lines","model:kb/disorders/Blastic_Plasmacytoid_Dendritic_Cell_Neoplasm.yaml:Tet2-edited HOXB8 dendritic differentiation culture"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Blastic_Plasmacytoid_Dendritic_Cell_Neoplasm.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Blastic_Plasmacytoid_Dendritic_Cell_Neoplasm.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Blastic_Plasmacytoid_Dendritic_Cell_Neoplasm.html#dataset-geo-gse261534"]},{"id":"dataset:geo:gse26155","accession":"geo:GSE26155","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE26155","title":"Advanced Study of Aortic Pathology (ASAP)","alternate_titles":[],"description":"Advanced Study of Aortic Pathology (ASAP) dataset comparing aortic tissue gene expression from patients with thoracic aortic aneurysms and bicuspid (BAV) vs tricuspid (TAV) aortic valves. Includes mammary artery controls and transplant donor samples.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0001515","label":"thoracic aorta","display_label":"thoracic aorta","url":"http://purl.obolibrary.org/obo/UBERON_0001515"}],"sample_type_labels":["thoracic aorta"],"sample_counts":[96],"sample_count":96,"conditions":["dilated aorta BAV","dilated aorta TAV","non-dilated aorta","mammary artery control"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["Affymetrix Human Exon 1.0 ST Array"],"platform":"Affymetrix Human Exon 1.0 ST Array","publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identifies immune response genes elevated in dilated TAV aortic tissue. Relevant for studying aortic aneurysm pathogenesis in connective tissue disorders including Marfan syndrome."],"contexts":[{"id":"disorder:Marfan_Syndrome","name":"Marfan Syndrome","kind":"Disorder","source_path":"kb/disorders/Marfan_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Marfan_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Marfan_Syndrome.html#dataset-geo-gse26155"}],"context_names":["Marfan Syndrome"],"disease_names":["Marfan Syndrome"],"disease_name":"Marfan Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Marfan_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Marfan_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Marfan_Syndrome.html#dataset-geo-gse26155"]},{"id":"dataset:geo:gse261617","accession":"geo:GSE261617","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE261617","title":"Iron supplementation alleviates pathologies in a mouse model of facioscapulohumeral muscular dystrophy","alternate_titles":[],"description":"Facioscapulohumeral muscular dystrophy (FSHD) is a genetic muscle disease caused by ectopic expression of the toxic protein DUX4, resulting in muscle weakness. However, the mechanism by which DUX4 exerts its toxicity remains unclear. In this study, we observed abnormal iron accumulation in muscles of patients with FSHD and in muscle-specific DUX4-expressing (DUX4-Tg) mice. Treatment with iron chelators, an iron-deficient diet, and genetic modifications inhibiting intracellular uptake of iron did not improve but rather exacerbated FSHD pathology in DUX4-Tg mice.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[23],"sample_count":23,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40591405"],"publication_contexts":[{"context_id":"disorder:Facioscapulohumeral_Muscular_Dystrophy","publication":"PMID:40591405"}],"publication":"PMID:40591405","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40591405","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Facioscapulohumeral Muscular Dystrophy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Facioscapulohumeral_Muscular_Dystrophy","name":"Facioscapulohumeral Muscular Dystrophy","kind":"Disorder","source_path":"kb/disorders/Facioscapulohumeral_Muscular_Dystrophy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Facioscapulohumeral_Muscular_Dystrophy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Facioscapulohumeral_Muscular_Dystrophy.html#dataset-geo-gse261617"}],"context_names":["Facioscapulohumeral Muscular Dystrophy"],"disease_names":["Facioscapulohumeral Muscular Dystrophy"],"disease_name":"Facioscapulohumeral Muscular Dystrophy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association 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SCA3."}],"notes":[],"contexts":[{"id":"disorder:Machado_Joseph_Disease","name":"Machado-Joseph Disease","kind":"Disorder","source_path":"kb/disorders/Machado_Joseph_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Machado_Joseph_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Machado-Joseph_Disease.html#dataset-geo-gse261670"}],"context_names":["Machado-Joseph Disease"],"disease_names":["Machado-Joseph Disease"],"disease_name":"Machado-Joseph Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association 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Psoriasis and AD are classically characterized by Th1/Th17 and Th2 polarization, respectively, but the neuroinflammatory profile of PN remains poorly defined. We characterized the neuroimmune phenotype of PN compared to AD, psoriasis, and healthy controls (HC), through transcriptomic analysis of lesional and nonlesional skin biopsies from 25 PN patients, 27 AD patients, 15 psoriasis patients, and 12 HC using a custom neuroinflammation-focused NanoString panel of 770 genes.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[120],"sample_count":120,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41333131"],"publication_contexts":[{"context_id":"disorder:Prurigo_Nodularis","publication":"PMID:41333131"}],"publication":"PMID:41333131","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41333131","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Prurigo Nodularis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Prurigo_Nodularis","name":"Prurigo Nodularis","kind":"Disorder","source_path":"kb/disorders/Prurigo_Nodularis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Prurigo_Nodularis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Prurigo_Nodularis.html#dataset-geo-gse261704"}],"context_names":["Prurigo Nodularis"],"disease_names":["Prurigo Nodularis"],"disease_name":"Prurigo Nodularis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Prurigo_Nodularis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Prurigo_Nodularis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Prurigo_Nodularis.html#dataset-geo-gse261704"]},{"id":"dataset:geo:gse261751","accession":"geo:GSE261751","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE261751","title":"Enterovirus-A71 Preferentially Infects and Replicates in Human Motor Neurons, Inducing Neurodegeneration by Ferroptosis","alternate_titles":[],"description":"Gene expression profiling of human motor neurons infected with EV-A71, investigating viral neurotropism and motor neuron vulnerability.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:39017655","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39017655","reference_title":"Enterovirus-A71 preferentially infects and replicates in human motor neurons, inducing neurodegeneration by ferroptosis.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Single cell transcriptomics of a mixed neuronal population reveal higher viral RNA load in motor neurons, suggesting higher infectivity and replication of EV-A71 in motor neurons.","explanation":"Supports this dataset as a human motor-neuron single-cell transcriptomic resource relevant to EV-A71 neurotropism."}],"notes":[],"contexts":[{"id":"disorder:Hand_Foot_and_Mouth_Disease","name":"Hand Foot and Mouth Disease","kind":"Disorder","source_path":"kb/disorders/Hand_Foot_and_Mouth_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hand_Foot_and_Mouth_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hand_Foot_and_Mouth_Disease.html#dataset-geo-gse261751"}],"context_names":["Hand Foot and Mouth Disease"],"disease_names":["Hand Foot and Mouth Disease"],"disease_name":"Hand Foot and Mouth Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hand_Foot_and_Mouth_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hand_Foot_and_Mouth_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hand_Foot_and_Mouth_Disease.html#dataset-geo-gse261751"]},{"id":"dataset:geo:gse262217","accession":"geo:GSE262217","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE262217","title":"Impaired B-cell function in ERCC2 deficiency","alternate_titles":[],"description":"Bulk mRNA sequencing of peripheral blood mononuclear cells from three unrelated patients with ERCC2-related TTD1 and five healthy controls. 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GSE262217 is linked to BioProject PRJNA1090832 and was released publicly on 2024-08-02; the repository describes expression profiling by high-throughput sequencing."],"contexts":[{"id":"disorder:Trichothiodystrophy","name":"Trichothiodystrophy","kind":"Disorder","source_path":"kb/disorders/Trichothiodystrophy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Trichothiodystrophy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Trichothiodystrophy.html#dataset-geo-gse262217"}],"context_names":["Trichothiodystrophy"],"disease_names":["Trichothiodystrophy"],"disease_name":"Trichothiodystrophy","same_context_model_ids":["model:kb/disorders/Trichothiodystrophy.yaml:ERCC2/ERCC3 patient-dermal-fibroblast R-loop model","model:kb/disorders/Trichothiodystrophy.yaml:GTF2E2-mutant patient iPSC-derived erythroid model","model:kb/disorders/Trichothiodystrophy.yaml:GTF2E2-mutant SV40-immortalized fibroblast temperature-challenge model","model:kb/disorders/Trichothiodystrophy.yaml:MPLKIP-deficient reconstructed human skin equivalent"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Trichothiodystrophy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Trichothiodystrophy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Trichothiodystrophy.html#dataset-geo-gse262217"]},{"id":"dataset:geo:gse262253","accession":"geo:GSE262253","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE262253","title":"Gene expression patterns in cMyBP-CΔC10mut HCM mice and cMyBP-C(t/t) DCM mice","alternate_titles":[],"description":"RNA-seq of the cMyBP-C(t/t) null mouse curated in this entry's animal models, alongside a transgenic mouse expressing a C10-domain mutant at roughly half the endogenous cMyBP-C level. The murine counterpart of the same allelic-dose contrast, with inflammatory pathway upregulation reported in the null hearts.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"house mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[4],"sample_count":4,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:7551","label":"MYBPC3","display_label":"MYBPC3","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/7551"}],"genes":["MYBPC3"],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE262253","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE262253","reference_title":"Gene expression patterns in cMyBP-CΔC10mut HCM mice and cMyBP-C(t/t) DCM mice","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"Similarly,to determine whether myocardial inflammation is associated with cardiac dysfunction in dilated cardiomyopathy (DCM) caused by MYBPC3 mutation, we used the well-characterized cMyBP-C(t/t) mouse model of DCM at 3months of age.","explanation":"Names the cMyBP-C(t/t) model curated under this entry's animal models and states what the null arm of the dataset measures. Quoted with the GEO summary's own missing spaces, as required."}],"notes":["The two arms are separate experiments in one series rather than a matched dose titration, and the null arm is sampled at 3 months, well past the neonatal window in which the human biallelic phenotype presents."],"contexts":[{"id":"disorder:Left_Ventricular_Noncompaction_10","name":"Left Ventricular Noncompaction 10","kind":"Disorder","source_path":"kb/disorders/Left_Ventricular_Noncompaction_10.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Left_Ventricular_Noncompaction_10.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Left_Ventricular_Noncompaction_10.html#dataset-geo-gse262253"}],"context_names":["Left Ventricular Noncompaction 10"],"disease_names":["Left Ventricular Noncompaction 10"],"disease_name":"Left Ventricular Noncompaction 10","same_context_model_ids":["model:kb/disorders/Left_Ventricular_Noncompaction_10.yaml:Biallelic MYBPC3 truncating hiPSC line with isogenic control","model:kb/disorders/Left_Ventricular_Noncompaction_10.yaml:Isogenic hiPSC-cardiomyocytes carrying MYBPC3 premature termination codon variants"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Left_Ventricular_Noncompaction_10.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Left_Ventricular_Noncompaction_10.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Left_Ventricular_Noncompaction_10.html#dataset-geo-gse262253"]},{"id":"dataset:geo:gse262882","accession":"geo:GSE262882","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE262882","title":"Activation of Fibroblast LRP1 by AT2-secreted MDK Affects OTUB1/SLC7A11 Ubiquitination to Inhibit Fibroblast Ferroptosis in Idiopathic Pulmonary Fibrosis.","alternate_titles":[],"description":"Idiopathic pulmonary fibrosis (IPF), a chronic interstitial fibrosing pneumonia of unknown cause, is characterized by an irreversible decrease in alveolar cells and an increase in fibroblasts. In our research, the numbers of AT2 cells and fibroblasts are abnormally regulated, but AT1 cells are significantly reduced in lung tissue sections from patients with IPF and mice. By analyzing the single-cell sequence from GEO database and experimental validation both in vivo and in vitro, it is found that the abnormally regulated AT2 cells secreting a large amount of MDK to activate the CTHRC1+ fibroblasts LRP1 receptor and inhibit the ferroptosis of fibroblasts.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42305620"],"publication_contexts":[{"context_id":"disorder:Idiopathic_Pulmonary_Fibrosis","publication":"PMID:42305620"}],"publication":"PMID:42305620","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42305620","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Idiopathic Pulmonary Fibrosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Idiopathic_Pulmonary_Fibrosis","name":"Idiopathic Pulmonary Fibrosis","kind":"Disorder","source_path":"kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Idiopathic_Pulmonary_Fibrosis.html#dataset-geo-gse262882"}],"context_names":["Idiopathic Pulmonary Fibrosis"],"disease_names":["Idiopathic Pulmonary Fibrosis"],"disease_name":"Idiopathic Pulmonary Fibrosis","same_context_model_ids":["model:kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml:Immune-cell-free AT2-lineage and fibroblast organoids","model:kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml:Microengineered alveolar array lung-on-chip with breathing mechanics"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Idiopathic_Pulmonary_Fibrosis.html#dataset-geo-gse262882"]},{"id":"dataset:geo:gse263272","accession":"geo:GSE263272","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE263272","title":"Human iPS cell-derived respiratory organoids as a model for respiratory syncytial virus infection","alternate_titles":[],"description":"Respiratory syncytial virus (RSV) is a seasonal respiratory pathogen that primarily affects young children, potentially causing severe lower respiratory tract disease. Despite the high disease burden, understanding of RSV pathophysiology remains limited. To address this, advanced RSV infection models are needed. While HEp-2 cells are widely used due to their high susceptibility to RSV, they do not accurately reflect the host response of the human respiratory tract.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40262853"],"publication_contexts":[{"context_id":"disorder:Respiratory_Syncytial_Virus_Infection","publication":"PMID:40262853"}],"publication":"PMID:40262853","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40262853","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Respiratory Syncytial Virus Infection (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Respiratory_Syncytial_Virus_Infection","name":"Respiratory Syncytial Virus Infection","kind":"Disorder","source_path":"kb/disorders/Respiratory_Syncytial_Virus_Infection.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Respiratory_Syncytial_Virus_Infection.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Respiratory_Syncytial_Virus_Infection.html#dataset-geo-gse263272"}],"context_names":["Respiratory Syncytial Virus Infection"],"disease_names":["Respiratory Syncytial Virus Infection"],"disease_name":"Respiratory Syncytial Virus Infection","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Respiratory_Syncytial_Virus_Infection.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Respiratory_Syncytial_Virus_Infection.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Respiratory_Syncytial_Virus_Infection.html#dataset-geo-gse263272"]},{"id":"dataset:geo:gse263666","accession":"geo:GSE263666","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE263666","title":"scRNAseq of CD8+ T cells from autoimmune encephalitis","alternate_titles":[],"description":"Single-cell RNA sequencing in seven anti-Ri autoimmune encephalitis (AIE) patients and three controls showed that neuron-reactive CD8+ T cells are cytotoxic KIR+ CD8+ regulatory T cells. In Ri-AIE, these cells had reduced KIR and IKZF2 (Helios) expression, alongside activated TCR signaling and elevated TNF and IFNG. They also overexpressed TOX, linked to brain-infiltrating cytotoxicity. These findings suggest a loss of regulatory function in KIR+ CD8+ T cells contributes to Ri-AIE pathogenesis.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[11],"sample_count":11,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41022795"],"publication_contexts":[{"context_id":"disorder:Autoimmune_Encephalitis","publication":"PMID:41022795"}],"publication":"PMID:41022795","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41022795","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Autoimmune Encephalitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Autoimmune_Encephalitis","name":"Autoimmune Encephalitis","kind":"Disorder","source_path":"kb/disorders/Autoimmune_Encephalitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autoimmune_Encephalitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autoimmune_Encephalitis.html#dataset-geo-gse263666"}],"context_names":["Autoimmune Encephalitis"],"disease_names":["Autoimmune Encephalitis"],"disease_name":"Autoimmune Encephalitis","same_context_model_ids":["model:kb/disorders/Autoimmune_Encephalitis.yaml:Chronic Patient-CSF Passive-Transfer Mouse Model","model:kb/disorders/Autoimmune_Encephalitis.yaml:Patient-CSF Hippocampal Neuron Culture Model"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Autoimmune_Encephalitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autoimmune_Encephalitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Autoimmune_Encephalitis.html#dataset-geo-gse263666"]},{"id":"dataset:geo:gse263736","accession":"geo:GSE263736","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE263736","title":"Development of an AAV-RNAi strategy to silence the dominant variant GNAO1 c.607G>A linked to encephalopathy","alternate_titles":[],"description":"RNA sequencing of patient-specific GABAergic neurons carrying the GNAO1 c.607G>A (p.G203R) hotspot variant, profiling the transcriptome consequences of AAV transduction, RNAi-machinery activation, and the allele-selective shRNA sh1500. The comparison the series was built for is a safety readout - off-target and vector-associated changes - so it reports on the therapeutic strategy at least as much as on the disease state, and the untreated patient-neuron arm is the part that speaks to the mechanism.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:4389","label":"GNAO1","display_label":"GNAO1","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/4389"}],"genes":["GNAO1"],"platforms":[],"platform":null,"publications":["PMID:40229422"],"publication_contexts":[{"context_id":"disorder:GNAO1-Related_Developmental_and_Epileptic_Encephalopathy","publication":"PMID:40229422"}],"publication":"PMID:40229422","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40229422","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Found by a targeted GEO DataSets title search for GNAO1; accession and metadata verified against NCBI E-utilities on 2026-08-27. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:GNAO1-Related_Developmental_and_Epileptic_Encephalopathy","name":"GNAO1-Related Developmental and Epileptic Encephalopathy","kind":"Disorder","source_path":"kb/disorders/GNAO1-Related_Developmental_and_Epileptic_Encephalopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/GNAO1-Related_Developmental_and_Epileptic_Encephalopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/GNAO1-Related_Developmental_and_Epileptic_Encephalopathy.html#dataset-geo-gse263736"}],"context_names":["GNAO1-Related Developmental and Epileptic Encephalopathy"],"disease_names":["GNAO1-Related Developmental and Epileptic Encephalopathy"],"disease_name":"GNAO1-Related Developmental and Epileptic Encephalopathy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/GNAO1-Related_Developmental_and_Epileptic_Encephalopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/GNAO1-Related_Developmental_and_Epileptic_Encephalopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/GNAO1-Related_Developmental_and_Epileptic_Encephalopathy.html#dataset-geo-gse263736"]},{"id":"dataset:geo:gse264100","accession":"geo:GSE264100","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE264100","title":"Resilience to Endoplasmic Reticulum Stress Mitigates Calcium-Dependent Membrane Hyperexcitability Underlying Late Disease Onset in Spinocerebellar Ataxia Type 6","alternate_titles":[],"description":"Bulk RNA-seq age series of SCA6 knock-in and wild-type mouse cerebellum used to identify unfolded-protein-response resilience and age-dependent ER-stress decompensation.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[40],"sample_count":40,"conditions":["SCA6 knock-in cerebellum at 3, 6, 12, and 19 months","Wild-type cerebellum at matched ages"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["Illumina NovaSeq"],"platform":"Illumina NovaSeq","publications":["PMID:40990218"],"publication_contexts":[{"context_id":"disorder:Autosomal_Dominant_Cerebellar_Ataxia_Type_III","publication":"PMID:40990218"}],"publication":"PMID:40990218","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40990218","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"url:https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE264100","reference_url":null,"reference_title":"GEO Accession viewer","supports":"SUPPORT","evidence_source":"OTHER","snippet":"Expression profiling by high throughput sequencing","explanation":"The GEO record identifies the dataset as sequencing-based expression profiling."},{"reference":"url:https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE264100","reference_url":null,"reference_title":"GEO Accession viewer","supports":"SUPPORT","evidence_source":"OTHER","snippet":"Samples (40)","explanation":"The GEO record reports 40 samples."}],"notes":[],"contexts":[{"id":"disorder:Autosomal_Dominant_Cerebellar_Ataxia_Type_III","name":"Autosomal Dominant Cerebellar Ataxia Type III","kind":"Disorder","source_path":"kb/disorders/Autosomal_Dominant_Cerebellar_Ataxia_Type_III.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autosomal_Dominant_Cerebellar_Ataxia_Type_III.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Dominant_Cerebellar_Ataxia_Type_III.html#dataset-geo-gse264100"}],"context_names":["Autosomal Dominant Cerebellar Ataxia Type III"],"disease_names":["Autosomal Dominant Cerebellar Ataxia Type III"],"disease_name":"Autosomal Dominant Cerebellar Ataxia Type III","same_context_model_ids":["model:kb/disorders/Autosomal_Dominant_Cerebellar_Ataxia_Type_III.yaml:SCA6 patient-derived iPSC Purkinje-cell model"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Autosomal_Dominant_Cerebellar_Ataxia_Type_III.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autosomal_Dominant_Cerebellar_Ataxia_Type_III.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Dominant_Cerebellar_Ataxia_Type_III.html#dataset-geo-gse264100"]},{"id":"dataset:geo:gse264182","accession":"geo:GSE264182","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE264182","title":"Iron-induced oxidative stress alters the transcriptome of bronchoalveolar lavage cells in silicosis","alternate_titles":[],"description":"Elevated iron levels are observed in silicosis patients, leading alveolar macrophages to increase ferritin production in response to this cellular stress. Our study employed a multi-omic approach to investigate how excess iron/ferritin influences the molecular profile of bronchoalveolar lavage (BAL) cells. Thirty-one participants were included, with RNA sequencing conducted on BAL cells from stone benchtop industry workers diagnosed with simple or complicated silicosis, compared to a cohort with no disease. BAL fluid (BALF) was analysed using gas chromatography-mass spectrometry (GC-MS) to screen for 498 volatile organic compounds (VOCs).","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[19],"sample_count":19,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39485079"],"publication_contexts":[{"context_id":"disorder:Silicosis","publication":"PMID:39485079"}],"publication":"PMID:39485079","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39485079","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Silicosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Silicosis","name":"Silicosis","kind":"Disorder","source_path":"kb/disorders/Silicosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Silicosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Silicosis.html#dataset-geo-gse264182"}],"context_names":["Silicosis"],"disease_names":["Silicosis"],"disease_name":"Silicosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Silicosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Silicosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Silicosis.html#dataset-geo-gse264182"]},{"id":"dataset:geo:gse264359","accession":"geo:GSE264359","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE264359","title":"A rare non-coding enhancer variant in SCN5A contributes to the high prevalence of Brugada syndrome in Thailand","alternate_titles":[],"description":"Brugada syndrome (BrS) is a cardiac arrhythmia disorder that causes sudden death in young adults. Rare genetic variants in the SCN5A gene, encoding the Nav1.5 sodium channel, and common non-coding variants at this locus, are robustly associated with the condition. BrS is particularly prevalent in Southeast Asia but the underlying ancestry-specific factors remain largely unknown. Methods: Genome sequencing of BrS probands and population-matched controls from Thailand was performed to identify rare non-coding variants at the SCN5A-SCN10A locus that were enriched in BrS cases.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[8],"sample_count":8,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39391988"],"publication_contexts":[{"context_id":"disorder:Brugada_Syndrome","publication":"PMID:39391988"}],"publication":"PMID:39391988","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39391988","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Brugada syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Brugada_Syndrome","name":"Brugada syndrome","kind":"Disorder","source_path":"kb/disorders/Brugada_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Brugada_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Brugada_syndrome.html#dataset-geo-gse264359"}],"context_names":["Brugada syndrome"],"disease_names":["Brugada syndrome"],"disease_name":"Brugada syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Brugada_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Brugada_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Brugada_syndrome.html#dataset-geo-gse264359"]},{"id":"dataset:geo:gse265851","accession":"geo:GSE265851","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE265851","title":"LAM cell mTOR dysregulation induces IL6 and paracrine AT2 cell senescence impeding lung repair in lymphangioleiomyomatosis.","alternate_titles":[],"description":"LAM is a rare disease which causes lung cysts and respiratory failure. TSC2 deficient ‘LAM cells’ with dysregulated mTOR signalling form nodules with fibroblasts causing lung injury. We examined if mTOR dysregulation could induce senescence and impair responses to lung injury. Senescence markers p21 and p16 were increased in LAM lungs and co-localised with alveolar type 2 cells. The SenMayo senescence gene panel was upregulated in LAM alveolar type 2 cells with senescence supressed by mTOR inhibition in patients. LAM cell / fibroblast spheroid cultures induced senescence markers in alveolar type 2 cell organoids, altered their growth and delayed epithelial scratch wound repair.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[30],"sample_count":30,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41068078"],"publication_contexts":[{"context_id":"disorder:Lymphangioleiomyomatosis","publication":"PMID:41068078"}],"publication":"PMID:41068078","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41068078","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Lymphangioleiomyomatosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Lymphangioleiomyomatosis","name":"Lymphangioleiomyomatosis","kind":"Disorder","source_path":"kb/disorders/Lymphangioleiomyomatosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Lymphangioleiomyomatosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Lymphangioleiomyomatosis.html#dataset-geo-gse265851"}],"context_names":["Lymphangioleiomyomatosis"],"disease_names":["Lymphangioleiomyomatosis"],"disease_name":"Lymphangioleiomyomatosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Lymphangioleiomyomatosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Lymphangioleiomyomatosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Lymphangioleiomyomatosis.html#dataset-geo-gse265851"]},{"id":"dataset:geo:gse266241","accession":"geo:GSE266241","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE266241","title":"Reduction of inhibitory signaling and selective induction of C-C motif chemokine ligands after spinal cord ischemia","alternate_titles":[],"description":"We used our mouse model of transient aortic cross clamping (ACC)-induced ischemic spinal cord injury (ISCI) to identify the early molecular changes in the spinal cord (SC) after ACC that contribute to delayed paraplegia in 65-70% of mice. SCs were collected one and four hours (h) after ACC, segmented into cervical and thoracic+lumbar (Th-Lu) sections, and RNA was sequenced. The non-ischemic cervical SC was used as control for the 1h post-ACC mice. At 4h, the transcriptome of ACC Th-Lu sections was compared with the transcriptome of sham Th-Lu.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[29],"sample_count":29,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Spinal Cord Ischemia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Spinal_Cord_Ischemia","name":"Spinal Cord Ischemia","kind":"Disorder","source_path":"kb/disorders/Spinal_Cord_Ischemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Spinal_Cord_Ischemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Spinal_Cord_Ischemia.html#dataset-geo-gse266241"}],"context_names":["Spinal Cord Ischemia"],"disease_names":["Spinal Cord Ischemia"],"disease_name":"Spinal Cord Ischemia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Spinal_Cord_Ischemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Spinal_Cord_Ischemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Spinal_Cord_Ischemia.html#dataset-geo-gse266241"]},{"id":"dataset:geo:gse266295","accession":"geo:GSE266295","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE266295","title":"A novel immunosenescent CD8+ T cell subset in patients with Ankylosing Spondylitis and Psoriatic Arthritis links spontaneous motility to telomere shortening and dysfunction","alternate_titles":[],"description":"Objectives: A pathogenetic role of CD8+ T lymphocytes in ankylosing spondylitis (AS) and other spondyloarthritis (SpA) is sustained by genome-wide association studies (GWAS) as well as the expansion of public T cell clonotypes in the target tissues. This study focuses on CD8+ T cells from AS and psoriatic arthritis (PsA) patients with the aim to correlate their phenotype and function with motility. Methods: Peripheral blood CD8+ and CD4+ T cells were isolated from AS (n= 128), PsA (n= 60) and rheumatoid arthritis (RA, n= 74) patients and healthy donors (HD, n= 79). Transwell migration assay was performed in the presence of different chemokines.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[16],"sample_count":16,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39835465"],"publication_contexts":[{"context_id":"disorder:Ankylosing_Spondylitis","publication":"PMID:39835465"},{"context_id":"disorder:Psoriatic_Arthritis","publication":"PMID:39835465"}],"publication":"PMID:39835465","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39835465","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Ankylosing Spondylitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.","Identified by GEO DataSets index search for Psoriatic Arthritis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Ankylosing_Spondylitis","name":"Ankylosing Spondylitis","kind":"Disorder","source_path":"kb/disorders/Ankylosing_Spondylitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ankylosing_Spondylitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Ankylosing_Spondylitis.html#dataset-geo-gse266295"},{"id":"disorder:Psoriatic_Arthritis","name":"Psoriatic Arthritis","kind":"Disorder","source_path":"kb/disorders/Psoriatic_Arthritis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Psoriatic_Arthritis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Psoriatic_Arthritis.html#dataset-geo-gse266295"}],"context_names":["Ankylosing Spondylitis","Psoriatic Arthritis"],"disease_names":["Ankylosing Spondylitis","Psoriatic Arthritis"],"disease_name":"Ankylosing Spondylitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Ankylosing_Spondylitis.yaml","kb/disorders/Psoriatic_Arthritis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ankylosing_Spondylitis.yaml","https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Psoriatic_Arthritis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Ankylosing_Spondylitis.html#dataset-geo-gse266295","https://dismech.monarchinitiative.org/pages/disorders/Psoriatic_Arthritis.html#dataset-geo-gse266295"]},{"id":"dataset:geo:gse266585","accession":"geo:GSE266585","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE266585","title":"Deconstruction of cellular dynamics after treatment of volumetric muscle loss injury with extracellular matrix","alternate_titles":[],"description":"Volumetric muscle loss (VML) is an acute loss of a critical volume of skeletal muscle that results in inflammation, fibrotic scarring in muscle tissue, and permanent muscle defects. The cellular and molecular processes that underlie fibrosis induced from VML injury need to be evaluated in larger animal models. Therefore, we used a canine model of VML alongside treatment with an extracellular matrix (ECM) hydrogel. Treatment with the ECM hydrogel improved muscle regenerative responses and decreased proportions and spatial signatures of fibrotic and inflammatory cell populations.","alternate_descriptions":[],"data_types":["SPATIAL_TRANSCRIPTOMICS"],"data_type_labels":["Spatially resolved transcriptomics"],"data_type_label":"Spatially resolved transcriptomics","organisms":[{"id":"NCBITaxon:9615","label":"Canis lupus familiaris","display_label":"dog","url":"http://purl.obolibrary.org/obo/NCBITaxon_9615"}],"organism_labels":["Canis lupus familiaris"],"organism_label":"Canis lupus familiaris","sample_types":[],"sample_type_labels":[],"sample_counts":[17],"sample_count":17,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41022770"],"publication_contexts":[{"context_id":"disorder:Volumetric_Muscle_Loss","publication":"PMID:41022770"}],"publication":"PMID:41022770","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41022770","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Volumetric Muscle Loss (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Volumetric_Muscle_Loss","name":"Volumetric Muscle Loss","kind":"Disorder","source_path":"kb/disorders/Volumetric_Muscle_Loss.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Volumetric_Muscle_Loss.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Volumetric_Muscle_Loss.html#dataset-geo-gse266585"}],"context_names":["Volumetric Muscle Loss"],"disease_names":["Volumetric Muscle Loss"],"disease_name":"Volumetric Muscle Loss","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Volumetric_Muscle_Loss.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Volumetric_Muscle_Loss.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Volumetric_Muscle_Loss.html#dataset-geo-gse266585"]},{"id":"dataset:geo:gse266789","accession":"geo:GSE266789","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE266789","title":"Early human fetal lung atlas reveals the temporal dynamics of epithelial cell plasticity [scRNAseq-hPSC]","alternate_titles":[],"description":"Early human fetal lung single-cell atlas dataset profiling over 150,000 cells from gestational weeks 10-19, with trajectories of CFTR-expressing progenitor populations and comparison to hPSC-derived fetal lung models.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0002048","label":"lung","display_label":"fetal lung tissue","url":"http://purl.obolibrary.org/obo/UBERON_0002048"}],"sample_type_labels":["lung"],"sample_counts":[19],"sample_count":19,"conditions":["normal fetal development"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39003323"],"publication_contexts":[{"context_id":"disorder:Cystic_Fibrosis","publication":"PMID:39003323"}],"publication":"PMID:39003323","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39003323","publication_status":"Publication recorded","findings":[{"statement":"Fetal lung development includes CFTR-high progenitor trajectories that inform developmental context for CFTR biology","evidence":[{"reference":"PMID:39003323","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39003323","reference_title":"Early human fetal lung atlas reveals the temporal dynamics of epithelial cell plasticity.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"We capture dynamic developmental trajectories from progenitor cells that express abundant levels of the cystic fibrosis conductance transmembrane regulator (CFTR).","explanation":"Establishes developmental CFTR-expressing progenitor trajectories relevant to CFTR biology."}]}],"findings_text":["Fetal lung development includes CFTR-high progenitor trajectories that inform developmental context for CFTR biology"],"evidence":[{"reference":"PMID:39003323","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39003323","reference_title":"Early human fetal lung atlas reveals the temporal dynamics of epithelial cell plasticity.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"We capture dynamic developmental trajectories from progenitor cells that express abundant levels of the cystic fibrosis conductance transmembrane regulator (CFTR).","explanation":"Establishes developmental CFTR-expressing progenitor trajectories relevant to CFTR biology."}],"notes":["Developmental fetal-lung atlas with explicit CFTR-expressing progenitor characterization."],"contexts":[{"id":"disorder:Cystic_Fibrosis","name":"Cystic Fibrosis","kind":"Disorder","source_path":"kb/disorders/Cystic_Fibrosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cystic_Fibrosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cystic_Fibrosis.html#dataset-geo-gse266789"}],"context_names":["Cystic Fibrosis"],"disease_names":["Cystic Fibrosis"],"disease_name":"Cystic Fibrosis","same_context_model_ids":["model:kb/disorders/Cystic_Fibrosis.yaml:CF airway-on-chip microphysiological model","model:kb/disorders/Cystic_Fibrosis.yaml:NuLi/CuFi airway epithelial cell-line model","model:kb/disorders/Cystic_Fibrosis.yaml:Patient-derived airway organoid theratyping model"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Cystic_Fibrosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cystic_Fibrosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cystic_Fibrosis.html#dataset-geo-gse266789"]},{"id":"dataset:geo:gse266862","accession":"geo:GSE266862","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE266862","title":"Single-cell RNA sequencing comparison of CD4+, CD8+ and T-cell receptor γδ+ cutaneous T-cell lymphomas reveals subset-specific molecular phenotypes","alternate_titles":[],"description":"Background: Malignant clones of primary cutaneous T-cell lymphomas (CTCL) can show a CD4+, CD8+ or T-cell receptor γδ+ phenotype, but their individual impact on tumor biology and skin lesion formation remains ill-defined. We perform a comprehensive molecular characterization of CD4+ vs. CD8+ and TCR-γ/δ+ CTCL lesions. Methods: We performed scRNA-seq of 18 CTCL skin biopsies to compare classic CD4+ advanced-stage mycosis fungoides (MF) with TCR-γ/δ+ MF and primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma (Berti’s lymphoma).","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[44],"sample_count":44,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39133553"],"publication_contexts":[{"context_id":"disorder:Primary_Cutaneous_Aggressive_Epidermotropic_CD8_T-cell_Lymphoma","publication":"PMID:39133553"}],"publication":"PMID:39133553","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39133553","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Primary Cutaneous Aggressive Epidermotropic CD8+ T-cell Lymphoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Primary_Cutaneous_Aggressive_Epidermotropic_CD8_T-cell_Lymphoma","name":"Primary Cutaneous Aggressive Epidermotropic CD8+ T-cell Lymphoma","kind":"Disorder","source_path":"kb/disorders/Primary_Cutaneous_Aggressive_Epidermotropic_CD8_T-cell_Lymphoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Primary_Cutaneous_Aggressive_Epidermotropic_CD8_T-cell_Lymphoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Cutaneous_Aggressive_Epidermotropic_CD8+_T-cell_Lymphoma.html#dataset-geo-gse266862"}],"context_names":["Primary Cutaneous Aggressive Epidermotropic CD8+ T-cell Lymphoma"],"disease_names":["Primary Cutaneous Aggressive Epidermotropic CD8+ T-cell Lymphoma"],"disease_name":"Primary Cutaneous Aggressive Epidermotropic CD8+ T-cell Lymphoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Primary_Cutaneous_Aggressive_Epidermotropic_CD8_T-cell_Lymphoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Primary_Cutaneous_Aggressive_Epidermotropic_CD8_T-cell_Lymphoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Primary_Cutaneous_Aggressive_Epidermotropic_CD8+_T-cell_Lymphoma.html#dataset-geo-gse266862"]},{"id":"dataset:geo:gse266943","accession":"geo:GSE266943","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE266943","title":"A humanized neuronal model system reveals key roles for the trace element manganese in neuronal endocytosis, calcium flux and mitochondrial bioenergetics","alternate_titles":[],"description":"Manganese (Mn) is an essential trace metal that is necessary for life. Its duality as both a crucial micronutrient and potential neurotoxicant necessitates tight control of intracellular and extracellular Mn levels. Dysregulation of Mn is implicated in a broad range of human diseases, from neurodevelopmental sequelae related to Mn levels in drinking water, to acquired forms of manganism, rare inherited Mn transportopathies and more common disorders such as Parkinson’s and Alzheimer’s disease. Despite the clear association between Mn dysregulation and neurodevelopmental or neurodegenerative diseases, the underlying cellular mechanisms that govern neuropathology remain poorly understood.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[48],"sample_count":48,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40917882"],"publication_contexts":[{"context_id":"disorder:Manganism","publication":"PMID:40917882"}],"publication":"PMID:40917882","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40917882","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Manganism (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Manganism","name":"Manganism","kind":"Disorder","source_path":"kb/disorders/Manganism.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Manganism.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Manganism.html#dataset-geo-gse266943"}],"context_names":["Manganism"],"disease_names":["Manganism"],"disease_name":"Manganism","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Manganism.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Manganism.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Manganism.html#dataset-geo-gse266943"]},{"id":"dataset:geo:gse267397","accession":"geo:GSE267397","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE267397","title":"A scalable gut epithelial organoid model reveals the genome-wide colonization landscape of a human-adapted pathogen","alternate_titles":[],"description":"Transcriptomics study using intestinal organoid model to characterize Shigella colonization mechanisms and host epithelial cell responses at the molecular level. Provides genome-wide insights into pathogen-host interactions during infection.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"Homo sapiens","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"CL:0002669","label":"intestinal epithelial cell","display_label":"intestinal epithelial cell","url":"http://purl.obolibrary.org/obo/CL_0002669"}],"sample_type_labels":["intestinal epithelial cell"],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40506541"],"publication_contexts":[{"context_id":"disorder:Shigellosis","publication":"PMID:40506541"}],"publication":"PMID:40506541","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40506541","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":[],"contexts":[{"id":"disorder:Shigellosis","name":"Shigellosis","kind":"Disorder","source_path":"kb/disorders/Shigellosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Shigellosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Shigellosis.html#dataset-geo-gse267397"}],"context_names":["Shigellosis"],"disease_names":["Shigellosis"],"disease_name":"Shigellosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Shigellosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Shigellosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Shigellosis.html#dataset-geo-gse267397"]},{"id":"dataset:geo:gse267834","accession":"geo:GSE267834","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE267834","title":"Hepatitis C Virus-induced Differential Transcriptional Traits in Host Cells After Persistent Infection Elimination by Direct-Acting Antivirals In Cell Culture","alternate_titles":[],"description":"Chronic hepatitis C virus infection (HCV) causes liver inflammation and fibrosis, leading to development of severe liver disease, such as cirrhosis or hepatocellular carcinoma (HCC). Approval of direct acting antiviral (DAA) drug combinations has revolutionized chronic HCV therapy, with virus eradication in >98% of the treated patients. The efficacy of these treatments is such that it is formally possible for cured patients to carry formerly infected cells that display irreversible transcriptional alterations directly caused by chronic HCV Infection.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[28],"sample_count":28,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:38988177"],"publication_contexts":[{"context_id":"disorder:Hepatitis_C","publication":"PMID:38988177"}],"publication":"PMID:38988177","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38988177","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Hepatitis C (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Hepatitis_C","name":"Hepatitis C","kind":"Disorder","source_path":"kb/disorders/Hepatitis_C.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatitis_C.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hepatitis_C.html#dataset-geo-gse267834"}],"context_names":["Hepatitis C"],"disease_names":["Hepatitis C"],"disease_name":"Hepatitis C","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hepatitis_C.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatitis_C.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hepatitis_C.html#dataset-geo-gse267834"]},{"id":"dataset:geo:gse267932","accession":"geo:GSE267932","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE267932","title":"Single-nucleus and spatial transcriptomics of human ovary: Molecular insights into signaling pathways underlying primary ovarian insufficiency in classic galactosemia","alternate_titles":[],"description":"Classic galactosemia (CG) is a rare inborn error of galactose metabolism caused by mutations in GALT gene. Primary ovarian insufficiency (POI) is a later complication that affects 80% of women with CG due to significant decline in ovarian follicle reserve. The definite mechanisms underlying the early onset of POI in CG patients is not fully understood. We utilized single-nucleus RNA sequencing (snRNA-seq) to generate a single-nucleus transcriptomic atlas of human ovaries from pre-pubertal girls with CG to investigate dynamic gene expression profiles in ovarian follicles and stromal cells.","alternate_descriptions":[],"data_types":["MULTI_OMICS"],"data_type_labels":["Multi Omics"],"data_type_label":"Multi Omics","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[9],"sample_count":9,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39440457"],"publication_contexts":[{"context_id":"disorder:Galactosemia","publication":"PMID:39440457"}],"publication":"PMID:39440457","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39440457","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Galactosemia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Galactosemia","name":"Galactosemia","kind":"Disorder","source_path":"kb/disorders/Galactosemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Galactosemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Galactosemia.html#dataset-geo-gse267932"}],"context_names":["Galactosemia"],"disease_names":["Galactosemia"],"disease_name":"Galactosemia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Galactosemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Galactosemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Galactosemia.html#dataset-geo-gse267932"]},{"id":"dataset:geo:gse268177","accession":"geo:GSE268177","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE268177","title":"Modulating alternative splicing of MECP2: A potential therapeutic strategy for Rett syndrome","alternate_titles":[],"description":"Rett syndrome (RTT) is a neurological disorder caused by loss-of-function mutations in methyl CpG binding protein 2 (MECP2), a transcriptional regulator essential for maintenance of normal neuronal function. The current FDA-approved treatment for RTT, Trofinetide, mildly alleviates some symptoms. In contrast, re-introducing MeCP2 or upregulating it through transgenesis in mouse RTT models improves most neurological phenotypes and enhances survival. Here, we devised a therapeutic strategy to moderately increase MeCP2 protein by modulating the alternative splicing of MECP2 to switch the less efficiently translated e2 to the more efficiently translated e1 isoform.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[93],"sample_count":93,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41779872"],"publication_contexts":[{"context_id":"disorder:Rett_Syndrome","publication":"PMID:41779872"}],"publication":"PMID:41779872","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41779872","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Rett Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Rett_Syndrome","name":"Rett Syndrome","kind":"Disorder","source_path":"kb/disorders/Rett_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rett_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Rett_Syndrome.html#dataset-geo-gse268177"}],"context_names":["Rett Syndrome"],"disease_names":["Rett Syndrome"],"disease_name":"Rett Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Rett_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rett_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Rett_Syndrome.html#dataset-geo-gse268177"]},{"id":"dataset:geo:gse268986","accession":"geo:GSE268986","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE268986","title":"Agonism of the glutamate receptor GluK2 suppresses dermal mast cell activation and cutaneous inflammation","alternate_titles":[],"description":"Mouse mast-cell transcriptomic dataset from a study of GluK2 agonism (SYM2081) as a suppressor of MrgprB2-driven mast cell activation, with in vivo validation in murine dermatitis and rosacea models. Aligns with the mast cell-mediated amplification node; rosacea is one of two disease models in the study, not its sole focus.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":["SYM2081-treated mast cells","vehicle-treated mast cells"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39661706"],"publication_contexts":[{"context_id":"disorder:Rosacea","publication":"PMID:39661706"}],"publication":"PMID:39661706","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39661706","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE268986","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE268986","reference_title":"Agonism of the glutamate receptor GluK2 suppresses dermal mast cell activation and cutaneous inflammation","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"Finally, pretreatment with SYM2081 significantly reduced skin inflammation in murine dermatitis and rosacea models.","explanation":"GEO summary reports rosacea-model validation of mast-cell-targeted suppression, relevant to the mast cell amplification step in this entry."}],"notes":[],"contexts":[{"id":"disorder:Rosacea","name":"Rosacea","kind":"Disorder","source_path":"kb/disorders/Rosacea.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rosacea.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Rosacea.html#dataset-geo-gse268986"}],"context_names":["Rosacea"],"disease_names":["Rosacea"],"disease_name":"Rosacea","same_context_model_ids":["model:kb/disorders/Rosacea.yaml:HaCaT keratinocytes under simulated rosacea conditions","model:kb/disorders/Rosacea.yaml:Paired lesional and non-lesional papulopustular rosacea skin explants","model:kb/disorders/Rosacea.yaml:SZ95 sebocyte and live Demodex mite co-culture"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Rosacea.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rosacea.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Rosacea.html#dataset-geo-gse268986"]},{"id":"dataset:geo:gse269047","accession":"geo:GSE269047","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE269047","title":"HERV activation segregates ME/CFS from fibromyalgia while defining a novel nosologic entity","alternate_titles":[],"description":"Research of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia (FM), two acquired chronic illnesses affecting mainly females, has failed to ascertain their frequent co-appearance and etiology. Despite prior detection of human endogenous retrovirus (HERV) activation in these diseases, the potential biomarker value of HERV expression profiles for their diagnosis, and the relationship of HERV expression profiles with patient immune systems and symptoms had remained unexplored.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[43],"sample_count":43,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40338225"],"publication_contexts":[{"context_id":"disorder:Fibromyalgia","publication":"PMID:40338225"}],"publication":"PMID:40338225","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40338225","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Fibromyalgia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Fibromyalgia","name":"Fibromyalgia","kind":"Disorder","source_path":"kb/disorders/Fibromyalgia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fibromyalgia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Fibromyalgia.html#dataset-geo-gse269047"}],"context_names":["Fibromyalgia"],"disease_names":["Fibromyalgia"],"disease_name":"Fibromyalgia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Fibromyalgia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fibromyalgia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Fibromyalgia.html#dataset-geo-gse269047"]},{"id":"dataset:geo:gse269117","accession":"geo:GSE269117","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE269117","title":"Multiomic-based Immune Response Profiling in Migraine, Vestibular Migraine and Meniere's Disease","alternate_titles":[],"description":"We analysed the immune profile of individuals with MI, VM, and MD using scRNAseq and scATACseq in PBMCs and to determine active biochemical pathways to identify new potential druggable molecular targets","alternate_descriptions":[],"data_types":["MULTI_OMICS"],"data_type_labels":["Multi Omics"],"data_type_label":"Multi Omics","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[24],"sample_count":24,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39294737"],"publication_contexts":[{"context_id":"disorder:Menieres_Disease","publication":"PMID:39294737"},{"context_id":"disorder:Migraine","publication":"PMID:39294737"}],"publication":"PMID:39294737","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39294737","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Meniere's Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values.","Identified by GEO DataSets index search for Migraine (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Menieres_Disease","name":"Meniere's Disease","kind":"Disorder","source_path":"kb/disorders/Menieres_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Menieres_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Meniere's_Disease.html#dataset-geo-gse269117"},{"id":"disorder:Migraine","name":"Migraine","kind":"Disorder","source_path":"kb/disorders/Migraine.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Migraine.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Migraine.html#dataset-geo-gse269117"}],"context_names":["Meniere's Disease","Migraine"],"disease_names":["Meniere's Disease","Migraine"],"disease_name":"Meniere's Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Menieres_Disease.yaml","kb/disorders/Migraine.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Menieres_Disease.yaml","https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Migraine.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Meniere's_Disease.html#dataset-geo-gse269117","https://dismech.monarchinitiative.org/pages/disorders/Migraine.html#dataset-geo-gse269117"]},{"id":"dataset:geo:gse269151","accession":"geo:GSE269151","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE269151","title":"Transcriptome immune-regulatory differences between leprosy patients and type 1 reaction patients, before onset of symptoms","alternate_titles":[],"description":"Leprosy is a chronic disease of the skin and peripheral nerves caused by Mycobacterium leprae. A major public health and clinical problem are leprosy reactions, which are inflammatory episodes that often contribute to nerve damage and disability. Type I reversal reactions (T1R) can occur after microbiological cure of leprosy and affect up to 50% of leprosy patients. Early intervention to prevent T1R and, hence, nerve damage, is a major focus of current leprosy control efforts. In this study, we compared transcript (i.e. isoform) expression and usage profiles from leprosy patients free of T1R at enrollment (who eventually developed T1R) against T1R-free leprosy patients.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[64],"sample_count":64,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39680574"],"publication_contexts":[{"context_id":"disorder:Leprosy","publication":"PMID:39680574"}],"publication":"PMID:39680574","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39680574","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Leprosy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Leprosy","name":"Leprosy","kind":"Disorder","source_path":"kb/disorders/Leprosy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Leprosy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Leprosy.html#dataset-geo-gse269151"}],"context_names":["Leprosy"],"disease_names":["Leprosy"],"disease_name":"Leprosy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Leprosy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Leprosy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Leprosy.html#dataset-geo-gse269151"]},{"id":"dataset:geo:gse269174","accession":"geo:GSE269174","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE269174","title":"Single cell lineage tracing of pulmonary endothelial cells in mouse model of Hereditary Hemorrhagic Telangiectasia 2","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"house mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[2],"sample_count":2,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39429196"],"publication_contexts":[{"context_id":"disorder:Hereditary_Hemorrhagic_Telangiectasia_Type_2","publication":"PMID:39429196"}],"publication":"PMID:39429196","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39429196","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Lineage-tracing arm of the endothelial Alk1 deletion study. Relevance triaged manually: the series names HHT2 explicitly and the model is Alk1, so this is the ACVRL1 genotype and not HHT generally."],"contexts":[{"id":"disorder:Hereditary_Hemorrhagic_Telangiectasia_Type_2","name":"Hereditary Hemorrhagic Telangiectasia Type 2","kind":"Disorder","source_path":"kb/disorders/Hereditary_Hemorrhagic_Telangiectasia_Type_2.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hereditary_Hemorrhagic_Telangiectasia_Type_2.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hereditary_Hemorrhagic_Telangiectasia_Type_2.html#dataset-geo-gse269174"}],"context_names":["Hereditary Hemorrhagic Telangiectasia Type 2"],"disease_names":["Hereditary Hemorrhagic Telangiectasia Type 2"],"disease_name":"Hereditary Hemorrhagic Telangiectasia Type 2","same_context_model_ids":["model:kb/disorders/Hereditary_Hemorrhagic_Telangiectasia_Type_2.yaml:LUMCi029-A-3 isogenic hiPSC line carrying ACVRL1 c.143G>A (p.Gly48Glu)"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Hereditary_Hemorrhagic_Telangiectasia_Type_2.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hereditary_Hemorrhagic_Telangiectasia_Type_2.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hereditary_Hemorrhagic_Telangiectasia_Type_2.html#dataset-geo-gse269174"]},{"id":"dataset:geo:gse26934","accession":"geo:GSE26934","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE26934","title":"Post-epidemic eosinophilia myalgia syndrome associated with L-Tryptophan","alternate_titles":[],"description":"Expression profiling by array of lesional skin from the 2011 post-epidemic case, against comparison samples. This is the source of the TGF-beta and IL-4 signalling signature reported in PMID:21702023, and it is the only EMS-specific dataset in GEO.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":["lesional skin from L-tryptophan-associated eosinophilia-myalgia syndrome"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:21702023"],"publication_contexts":[{"context_id":"disorder:Eosinophilia-Myalgia_Syndrome","publication":"PMID:21702023"}],"publication":"PMID:21702023","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/21702023","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE26934","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE26934","reference_title":"Post-epidemic eosinophilia myalgia syndrome associated with L-Tryptophan","supports":"SUPPORT","evidence_source":"OTHER","snippet":"The EMS epidemic in 1989 was linked to L-tryptophan consumption originating from a single source.","explanation":"The GEO record's own summary establishes the series is about this disease and this exposure, which is the relevance check an accession resolving does not supply."}],"notes":["Six samples from a single post-epidemic case and its comparisons, so the series is a case-level profiling experiment rather than a cohort. The signature it carries is curated on `Fibroblast Activation and Type I Collagen Overproduction` as a `PMID:21702023` evidence item; an earlier draft of this note said so before that item existed, which made the note a false statement about the entry. The evidence item quotes the publication rather than this GEO record because the GEO summary states the disease and the exposure and not the result."],"contexts":[{"id":"disorder:Eosinophilia-Myalgia_Syndrome","name":"Eosinophilia-Myalgia Syndrome","kind":"Disorder","source_path":"kb/disorders/Eosinophilia-Myalgia_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Eosinophilia-Myalgia_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Eosinophilia-Myalgia_Syndrome.html#dataset-geo-gse26934"}],"context_names":["Eosinophilia-Myalgia Syndrome"],"disease_names":["Eosinophilia-Myalgia Syndrome"],"disease_name":"Eosinophilia-Myalgia Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Eosinophilia-Myalgia_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Eosinophilia-Myalgia_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Eosinophilia-Myalgia_Syndrome.html#dataset-geo-gse26934"]},{"id":"dataset:geo:gse269535","accession":"geo:GSE269535","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE269535","title":"Defective mitochondrial COX1 translation due to loss of COX14 function triggers ROS-induced inflammation in mouse liver","alternate_titles":[],"description":"Bulk liver transcriptomics comparing wild-type and homozygous COX14 Met19Ile mice. 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Expression differences do not by themselves establish motor-neuron causal pathways."],"contexts":[{"id":"disorder:Amyotrophic_Lateral_Sclerosis_Type_1","name":"Amyotrophic Lateral Sclerosis Type 1","kind":"Disorder","source_path":"kb/disorders/Amyotrophic_Lateral_Sclerosis_Type_1.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Amyotrophic_Lateral_Sclerosis_Type_1.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Amyotrophic_Lateral_Sclerosis_Type_1.html#dataset-geo-gse271030"}],"context_names":["Amyotrophic Lateral Sclerosis Type 1"],"disease_names":["Amyotrophic Lateral Sclerosis Type 1"],"disease_name":"Amyotrophic Lateral Sclerosis Type 1","same_context_model_ids":["model:kb/disorders/Amyotrophic_Lateral_Sclerosis_Type_1.yaml:ATP-triggered SOD1 donor and recipient cultures","model:kb/disorders/Amyotrophic_Lateral_Sclerosis_Type_1.yaml:Embryonic spinal-cord SOD1 toxicity and rescue cultures","model:kb/disorders/Amyotrophic_Lateral_Sclerosis_Type_1.yaml:Mutant SOD1 Derlin-1 and ERAD assays","model:kb/disorders/Amyotrophic_Lateral_Sclerosis_Type_1.yaml:WTC11 motor-neuron transcription-factor perturbation"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Amyotrophic_Lateral_Sclerosis_Type_1.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Amyotrophic_Lateral_Sclerosis_Type_1.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Amyotrophic_Lateral_Sclerosis_Type_1.html#dataset-geo-gse271030"]},{"id":"dataset:geo:gse271179","accession":"geo:GSE271179","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE271179","title":"Transcriptome analysis of cell line/patient-derived xenograft (PDX) samples of myeloid leukemia associated with Down syndrome (ML-DS)","alternate_titles":[],"description":"Myeloid leukemia associated with Down syndrome (ML-DS) is a rare pediatric cancer in which 10-20% patients who are relapsed/refractory have very limited treatment options. 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Total RNA that was purified from glomeruli which were extracted from mutant and wild type kidneys was measured and then converted into first strand cDNA. qPCR was followed by using the instrument-specific and ready-to-use RT2 qPCR Master Mixes and gene specific primer sets.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[9],"sample_count":9,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40484355"],"publication_contexts":[{"context_id":"disorder:Alport_Syndrome","publication":"PMID:40484355"}],"publication":"PMID:40484355","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40484355","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Alport Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. 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The mechanisms that determine these persistent muscle problems are not well known. We aimed to identify circulating microRNAs (miRNAs) with differential expression that could be potential biomarkers for the diagnosis and/or prognosis in Cushing's syndrome.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[36],"sample_count":36,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39086897"],"publication_contexts":[{"context_id":"disorder:Cushings_Syndrome","publication":"PMID:39086897"}],"publication":"PMID:39086897","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39086897","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Cushing's Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Cushings_Syndrome","name":"Cushing's Syndrome","kind":"Disorder","source_path":"kb/disorders/Cushings_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cushings_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cushing's_Syndrome.html#dataset-geo-gse271649"}],"context_names":["Cushing's Syndrome"],"disease_names":["Cushing's Syndrome"],"disease_name":"Cushing's Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cushings_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cushings_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cushing's_Syndrome.html#dataset-geo-gse271649"]},{"id":"dataset:geo:gse271780","accession":"geo:GSE271780","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE271780","title":"Identification of apelin/APJ signaling dysregulation in a human iPSC-derived granulosa cell model of Turner syndrome","alternate_titles":[],"description":"Bulk RNA sequencing of day-14 granulosa-like cells differentiated from 45,X Turner and unaffected-control iPSCs, with adult cumulus granulosa cells used in the study as a reference population.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"CL:0000501","label":"granulosa cell","display_label":"granulosa cell","url":"http://purl.obolibrary.org/obo/CL_0000501"}],"sample_type_labels":["granulosa cell"],"sample_counts":[10],"sample_count":10,"conditions":["2 unaffected-control iPSC-derived granulosa-like cell lines","4 45,X Turner syndrome iPSC-derived granulosa-like cell subclones from 2 source donors (2 subclones per donor)","4 adult luteinized cumulus granulosa-cell reference samples"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["Illumina NovaSeq 6000"],"platform":"Illumina NovaSeq 6000","publications":["PMID:39543104"],"publication_contexts":[{"context_id":"disorder:Turner_Syndrome","publication":"PMID:39543104"}],"publication":"PMID:39543104","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39543104","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:39543104","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39543104","reference_title":"Identification of apelin/APJ signaling dysregulation in a human iPSC-derived granulosa cell model of Turner syndrome.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The raw data was deposited in GEO: GSE271780.","explanation":"Direct accession statement from the primary publication."}],"notes":["Direct disease-model dataset discovered with `just discover-datasets`; accession, organism, publication, data type, NovaSeq platform, and 10-sample three-group composition verified against NCBI GEO metadata on 2026-08-16."],"contexts":[{"id":"disorder:Turner_Syndrome","name":"Turner Syndrome","kind":"Disorder","source_path":"kb/disorders/Turner_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Turner_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Turner_Syndrome.html#dataset-geo-gse271780"}],"context_names":["Turner Syndrome"],"disease_names":["Turner Syndrome"],"disease_name":"Turner Syndrome","same_context_model_ids":["model:kb/disorders/Turner_Syndrome.yaml:45,X patient-derived iPSC cardiomyocytes","model:kb/disorders/Turner_Syndrome.yaml:45,X patient-derived iPSC granulosa-like cells"],"candidate_model_ids":["model:kb/disorders/Turner_Syndrome.yaml:45,X patient-derived iPSC granulosa-like cells"],"association_basis":"Same publication as a NAM (candidate)","nam_disease_context":"Same publication as a NAM (candidate)","source_paths":["kb/disorders/Turner_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Turner_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Turner_Syndrome.html#dataset-geo-gse271780"]},{"id":"dataset:geo:gse271789","accession":"geo:GSE271789","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE271789","title":"Single-Cell Analysis Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitis","alternate_titles":[],"description":"Single-cell and single-nucleus RNA-seq of PBMCs and BAL cells from fibrotic hypersensitivity pneumonitis, idiopathic pulmonary fibrosis, and controls. The HP cohort is not stratified by inciting antigen.","alternate_descriptions":["Rationale: Fibrotic hypersensitivity pneumonitis is a debilitating interstitial lung disease driven by incompletely understood immune mechanisms. Objectives: To elucidate immune aberrations in fibrotic hypersensitivity pneumonitis in single-cell resolution. Methods: Single-cell 5’ RNA sequencing was conducted on peripheral blood mononuclear cells and bronchoalveolar lavage cells obtained from 45 patients with fibrotic hypersensitivity pneumonitis, 63 idiopathic pulmonary fibrosis, 4 non-fibrotic hypersensitivity pneumonitis, and 36 healthy controls in the United States and Mexico."],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"CL:2000001","label":"peripheral blood mononuclear cell","display_label":"peripheral blood mononuclear cell","url":"http://purl.obolibrary.org/obo/CL_2000001"},{"id":"NCIT:C13195","label":"Bronchoalveolar Lavage Fluid","display_label":"bronchoalveolar lavage","url":"http://purl.obolibrary.org/obo/NCIT_C13195"}],"sample_type_labels":["peripheral blood mononuclear cell","Bronchoalveolar Lavage Fluid"],"sample_counts":[76],"sample_count":76,"conditions":["fibrotic hypersensitivity pneumonitis","idiopathic pulmonary fibrosis","healthy control"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:38924775"],"publication_contexts":[{"context_id":"disorder:Bird_Fanciers_Lung","publication":"PMID:38924775"},{"context_id":"disorder:Hypersensitivity_Pneumonitis","publication":"PMID:38924775"}],"publication":"PMID:38924775","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38924775","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:38924775","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/38924775","reference_title":"Single-Cell Analysis Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitis.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"Single-cell 5' RNA sequencing was conducted on peripheral blood mononuclear cells and BAL cells obtained from 45 patients with FHP, 63 patients with idiopathic pulmonary fibrosis (IPF), 4 patients with nonfibrotic hypersensitivity pneumonitis, and 36 healthy control subjects in the United States and Mexico.","explanation":"The abstract documents single-cell sequencing of PBMC and BAL cells from fibrotic HP, IPF, and controls, aligning with the dataset."}],"notes":["GEO record linked to the AJRCCM 2024 single-cell study profiling PBMC and BAL; it informs shared fibrotic-HP mechanisms rather than a proven avian-specific program.","Identified by GEO DataSets index search for Hypersensitivity pneumonitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Bird_Fanciers_Lung","name":"Bird Fancier's Lung","kind":"Disorder","source_path":"kb/disorders/Bird_Fanciers_Lung.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bird_Fanciers_Lung.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Bird_Fancier's_Lung.html#dataset-geo-gse271789"},{"id":"disorder:Hypersensitivity_Pneumonitis","name":"Hypersensitivity pneumonitis","kind":"Disorder","source_path":"kb/disorders/Hypersensitivity_Pneumonitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hypersensitivity_Pneumonitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hypersensitivity_pneumonitis.html#dataset-geo-gse271789"}],"context_names":["Bird Fancier's Lung","Hypersensitivity pneumonitis"],"disease_names":["Bird Fancier's Lung","Hypersensitivity pneumonitis"],"disease_name":"Bird Fancier's Lung","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Bird_Fanciers_Lung.yaml","kb/disorders/Hypersensitivity_Pneumonitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bird_Fanciers_Lung.yaml","https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hypersensitivity_Pneumonitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Bird_Fancier's_Lung.html#dataset-geo-gse271789","https://dismech.monarchinitiative.org/pages/disorders/Hypersensitivity_pneumonitis.html#dataset-geo-gse271789"]},{"id":"dataset:geo:gse271866","accession":"geo:GSE271866","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE271866","title":"Unveiling Cancer-Related Metaplastic Cells in Both Helicobacter pylori Infection and Autoimmune Gastritis","alternate_titles":[],"description":"We used 10X 5' single cell RNA sequencing (scRNAseq) technology to examine the transcriptional profiles of distinct gastric metaplastic cell types within the gastric corpus of mice chronically infected with Helicobacter pylori or chronically inflamed with autoimmune gastritis and humans with autoimmune gastritis.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[7],"sample_count":7,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39236896"],"publication_contexts":[{"context_id":"disorder:Autoimmune_Gastritis","publication":"PMID:39236896"}],"publication":"PMID:39236896","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39236896","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Autoimmune Gastritis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Autoimmune_Gastritis","name":"Autoimmune Gastritis","kind":"Disorder","source_path":"kb/disorders/Autoimmune_Gastritis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autoimmune_Gastritis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autoimmune_Gastritis.html#dataset-geo-gse271866"}],"context_names":["Autoimmune Gastritis"],"disease_names":["Autoimmune Gastritis"],"disease_name":"Autoimmune Gastritis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Autoimmune_Gastritis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autoimmune_Gastritis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Autoimmune_Gastritis.html#dataset-geo-gse271866"]},{"id":"dataset:geo:gse272062","accession":"geo:GSE272062","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE272062","title":"Lysophosphatidic acid (LPA)-dependent propagation of neuroinflammation in an optimized model of post-hemorrhagic hydrocephalus","alternate_titles":[],"description":"Single-cell transcriptomics in a mouse model of post-haemorrhagic hydrocephalus, relevant to the intraventricular-haemorrhage and choroid plexus inflammatory nodes of this entry.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"house mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40971013"],"publication_contexts":[{"context_id":"disorder:Congenital_Hydrocephalus","publication":"PMID:40971013"}],"publication":"PMID:40971013","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40971013","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Discovered with just discover-datasets (DIRECT) and resolved with just verify-datasets. Model-organism dataset; relevance triaged manually against the post-haemorrhagic subtype."],"contexts":[{"id":"disorder:Congenital_Hydrocephalus","name":"Congenital Hydrocephalus","kind":"Disorder","source_path":"kb/disorders/Congenital_Hydrocephalus.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Congenital_Hydrocephalus.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Congenital_Hydrocephalus.html#dataset-geo-gse272062"}],"context_names":["Congenital Hydrocephalus"],"disease_names":["Congenital Hydrocephalus"],"disease_name":"Congenital Hydrocephalus","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Congenital_Hydrocephalus.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Congenital_Hydrocephalus.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Congenital_Hydrocephalus.html#dataset-geo-gse272062"]},{"id":"dataset:geo:gse272125","accession":"geo:GSE272125","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE272125","title":"Transfer RNAs, not microRNAs, are linked to ischemic stroke and major bleeding in patients with end-stage kidney disease","alternate_titles":[],"description":"Background: Patients with end-stage kidney disease (ESKD) are at very high risk for thromboembolism and bleeding. This study aimed to identify small non-coding RNAs (sncRNAs), specifically microRNAs and transfer-RNA (tRNA)-derived fragments (tRFs), as potential novel biomarkers for predicting thromboembolism and bleeding in this high-risk population. Methods: In this sncRNA discovery research, we leveraged the VIVALDI cohort, consisting of 625 ESKD patients on hemodialysis, to conduct two nested case-control studies, each comprising 18 participants. The primary outcomes were ischemic stroke in the first study and major bleeding in the second.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[34],"sample_count":34,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39260398"],"publication_contexts":[{"context_id":"disorder:Chronic_Kidney_Disease","publication":"PMID:39260398"},{"context_id":"disorder:Ischemic_Stroke","publication":"PMID:39260398"}],"publication":"PMID:39260398","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39260398","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Chronic Kidney Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values.","Identified by GEO DataSets index search for Ischemic Stroke (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Chronic_Kidney_Disease","name":"Chronic Kidney Disease","kind":"Disorder","source_path":"kb/disorders/Chronic_Kidney_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Kidney_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chronic_Kidney_Disease.html#dataset-geo-gse272125"},{"id":"disorder:Ischemic_Stroke","name":"Ischemic Stroke","kind":"Disorder","source_path":"kb/disorders/Ischemic_Stroke.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ischemic_Stroke.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Ischemic_Stroke.html#dataset-geo-gse272125"}],"context_names":["Chronic Kidney Disease","Ischemic Stroke"],"disease_names":["Chronic Kidney Disease","Ischemic Stroke"],"disease_name":"Chronic Kidney Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chronic_Kidney_Disease.yaml","kb/disorders/Ischemic_Stroke.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Kidney_Disease.yaml","https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ischemic_Stroke.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chronic_Kidney_Disease.html#dataset-geo-gse272125","https://dismech.monarchinitiative.org/pages/disorders/Ischemic_Stroke.html#dataset-geo-gse272125"]},{"id":"dataset:geo:gse272142","accession":"geo:GSE272142","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE272142","title":"Genome‑wideBrain DNAMethylationandGeneExpression Patterns Unravel Epigenetic Reprogramming in Mesial Temporal Lobe Epilepsy","alternate_titles":[],"description":"Mesial temporal lobe epilepsy (MTLE) is the most common drug-resistant epilepsy in adults, characterized by hippocampus sclerosis. To date, the etiology of MTLE epileptogenesis and the molecular mechanisms underlying hippocampus sclerosis remain largely unclear. Altered genome-wide DNA methylation patterns and differential gene expression have been reported to be involved in the pathophysiological mechanism of epileptogenesis. To discover epigenetic reprogramming patterns associated with MTLE, we used a higher-throughput microarray, Illumina Infinium 850 K BeadChip, and RNA sequence to analyze epigenome-wide DNA methylation and related gene expressions.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Temporal Lobe Epilepsy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Temporal_Lobe_Epilepsy","name":"Temporal Lobe Epilepsy","kind":"Disorder","source_path":"kb/disorders/Temporal_Lobe_Epilepsy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Temporal_Lobe_Epilepsy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Temporal_Lobe_Epilepsy.html#dataset-geo-gse272142"}],"context_names":["Temporal Lobe Epilepsy"],"disease_names":["Temporal Lobe Epilepsy"],"disease_name":"Temporal Lobe Epilepsy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Temporal_Lobe_Epilepsy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Temporal_Lobe_Epilepsy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Temporal_Lobe_Epilepsy.html#dataset-geo-gse272142"]},{"id":"dataset:geo:gse272189","accession":"geo:GSE272189","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE272189","title":"Gene expression profile at single cell level of human nasal primary airway cells from DNAH5 subjects","alternate_titles":[],"description":"Public human nasal ALI-culture scRNA-seq series linked to PMID:39042459. GEO lists 15 samples; the primary discovery comparison includes four DNAH5 PCD donors, their four heterozygous mothers and five unrelated controls, with additional samples represented in the accession. Sample count is not an independent patient count. Cultured and iPSC validation identified oxidative stress and ciliary GSTA2 responses; no independent raw-data reanalysis was performed in this curation.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:2950","label":"DNAH5","display_label":"DNAH5","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/2950"}],"genes":["DNAH5"],"platforms":[],"platform":null,"publications":["PMID:39042459"],"publication_contexts":[{"context_id":"disorder:Primary_Ciliary_Dyskinesia","publication":"PMID:39042459"}],"publication":"PMID:39042459","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39042459","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:39042459","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39042459","reference_title":"Transcriptional analysis of primary ciliary dyskinesia airway cells reveals a dedicated cilia glutathione pathway.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We used single-cell RNA-Seq, proteomics, and advanced microscopy to compare primary culture epithelial cells from patients with PCD, their heterozygous mothers, and healthy individuals","explanation":"Single-cell transcriptomic dataset of human PCD airway epithelial cells (DNAH5 patients) versus heterozygous mothers and controls."}],"notes":[],"contexts":[{"id":"disorder:Primary_Ciliary_Dyskinesia","name":"Primary_Ciliary_Dyskinesia","kind":"Disorder","source_path":"kb/disorders/Primary_Ciliary_Dyskinesia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Primary_Ciliary_Dyskinesia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Ciliary_Dyskinesia.html#dataset-geo-gse272189"}],"context_names":["Primary_Ciliary_Dyskinesia"],"disease_names":["Primary_Ciliary_Dyskinesia"],"disease_name":"Primary_Ciliary_Dyskinesia","same_context_model_ids":["model:kb/disorders/Primary_Ciliary_Dyskinesia.yaml:BCi-NS1.1 dyskinetic airway epithelial cell line","model:kb/disorders/Primary_Ciliary_Dyskinesia.yaml:BMI1-expanded DNAH5 patient airway epithelial cell model","model:kb/disorders/Primary_Ciliary_Dyskinesia.yaml:C1d-defective patient airway transport model","model:kb/disorders/Primary_Ciliary_Dyskinesia.yaml:CCDC40 mRNA replacement in patient airway cultures","model:kb/disorders/Primary_Ciliary_Dyskinesia.yaml:DNAH5 patient redox profiling and separate GSTA2 airway-cell perturbation","model:kb/disorders/Primary_Ciliary_Dyskinesia.yaml:GAS2L2-deficient patient nasal epithelial orientation model","model:kb/disorders/Primary_Ciliary_Dyskinesia.yaml:iPSC-derived microfluidic airway-on-a-chip model","model:kb/disorders/Primary_Ciliary_Dyskinesia.yaml:Mixed wild-type and CCDC40-deficient airway epithelial cultures","model:kb/disorders/Primary_Ciliary_Dyskinesia.yaml:Patient-derived airway organoid model","model:kb/disorders/Primary_Ciliary_Dyskinesia.yaml:Patient-derived nasal epithelial air-liquid interface model","model:kb/disorders/Primary_Ciliary_Dyskinesia.yaml:Patient-specific hiPSC-derived airway epithelium model"],"candidate_model_ids":["model:kb/disorders/Primary_Ciliary_Dyskinesia.yaml:DNAH5 patient redox profiling and separate GSTA2 airway-cell perturbation"],"association_basis":"Same publication as a NAM (candidate)","nam_disease_context":"Same publication as a NAM (candidate)","source_paths":["kb/disorders/Primary_Ciliary_Dyskinesia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Primary_Ciliary_Dyskinesia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Primary_Ciliary_Dyskinesia.html#dataset-geo-gse272189"]},{"id":"dataset:geo:gse272226","accession":"geo:GSE272226","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE272226","title":"Tumor RNA sequencing identifies a group of Mycosis Fungoides patients with failure of skin-directed therapies","alternate_titles":[],"description":"Mycosis fungoides (MF), the most common type of primary cutaneous T-cell lymphoma, has a heterogeneous clinical course, and the factors determining disease progression from the indolent to the aggressive disease stages are not well known. Our previous study described prognostic groups of MF cases according to the transcription factors Twist and Zeb1. Using Twist expression, we differentiated distinct groups based on their global RNA expression. Using the same dataset with 40 formalin-fixed paraffin-embedded MF samples, we performed RNA sequencing using bioinformatics tools. Based on the consensus clustering, we defined four clusters with different disease pathologies and prognostic groups.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[48],"sample_count":48,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39245139"],"publication_contexts":[{"context_id":"disorder:Mycosis_Fungoides","publication":"PMID:39245139"}],"publication":"PMID:39245139","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39245139","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Mycosis Fungoides (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Mycosis_Fungoides","name":"Mycosis Fungoides","kind":"Disorder","source_path":"kb/disorders/Mycosis_Fungoides.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mycosis_Fungoides.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Mycosis_Fungoides.html#dataset-geo-gse272226"}],"context_names":["Mycosis Fungoides"],"disease_names":["Mycosis Fungoides"],"disease_name":"Mycosis Fungoides","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Mycosis_Fungoides.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mycosis_Fungoides.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Mycosis_Fungoides.html#dataset-geo-gse272226"]},{"id":"dataset:geo:gse272426","accession":"geo:GSE272426","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE272426","title":"Immunological landscape of human lymphoid explants during measles virus infection [BulkSeq]","alternate_titles":[],"description":"In humans, lymph nodes are the primary site of measles virus (MeV) replication. To understand the immunological events that occur at this site, we infected human lymphoid tissue explants using a pathogenic strain of MeV that expresses GFP. We found that MeV infected between 5-15% of cells across donors. Using single cell RNA-Seq (scRNA-Seq) and flow cytometry, we found that while most of the 29 cell populations identified in the lymphoid culture were susceptible to MeV, there was a broad preferential infection of B cells and reduced infection of T cells. Further subsetting of T cells revealed that this reduction may be driven by the decreased infection of naïve T cells.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39253971"],"publication_contexts":[{"context_id":"disorder:Measles","publication":"PMID:39253971"}],"publication":"PMID:39253971","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39253971","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Measles (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Measles","name":"Measles","kind":"Disorder","source_path":"kb/disorders/Measles.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Measles.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Measles.html#dataset-geo-gse272426"}],"context_names":["Measles"],"disease_names":["Measles"],"disease_name":"Measles","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Measles.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Measles.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Measles.html#dataset-geo-gse272426"]},{"id":"dataset:geo:gse272560","accession":"geo:GSE272560","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE272560","title":"A measles virus collective infectious unit that caused lethal human brain disease includes many locally restricted and few widespread copy-back defective genomes","alternate_titles":[],"description":"During virus replication in cultured cells, copy-back defective viral genomes (cbDVG) can arise. CbDVG are powerful inducers of innate immune responses in vitro, but their occurrence and impact on natural infections of human hosts remain poorly defined. We asked whether cbDVG were generated in the brain of a patient who succumbed to subacute sclerosing panencephalitis (SSPE) about 20 years after acute measles virus (MeV) infection. Previous analyses of 13 brain specimens of this patient indicated that a collective infectious unit (CIU) drove lethal MeV spread. In this study, we identified 276 replication-competent cbDVG species, each present in over 100 copies in the brain.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[16],"sample_count":16,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39431848"],"publication_contexts":[{"context_id":"disorder:Measles","publication":"PMID:39431848"}],"publication":"PMID:39431848","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39431848","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Measles (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Measles","name":"Measles","kind":"Disorder","source_path":"kb/disorders/Measles.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Measles.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Measles.html#dataset-geo-gse272560"}],"context_names":["Measles"],"disease_names":["Measles"],"disease_name":"Measles","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Measles.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Measles.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Measles.html#dataset-geo-gse272560"]},{"id":"dataset:geo:gse272589","accession":"geo:GSE272589","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE272589","title":"Zebrafish Cyp1b1 knockout alters eye and brain metabolomic profiles, affecting ocular and neurobehavioral function","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:7955","label":"Danio rerio","display_label":"zebrafish","url":"http://purl.obolibrary.org/obo/NCBITaxon_7955"}],"organism_labels":["Danio rerio"],"organism_label":"Danio rerio","sample_types":[],"sample_type_labels":[],"sample_counts":[40],"sample_count":40,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39890032"],"publication_contexts":[{"context_id":"disorder:Congenital_Glaucoma","publication":"PMID:39890032"}],"publication":"PMID:39890032","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39890032","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Cyp1b1 loss-of-function zebrafish, explicitly framed by its authors around the unresolved role of CYP1B1 in primary congenital glaucoma -- relevant to the metabolic-route question recorded in the cyp1b1_expression_site discussion. Verified against NCBI E-utilities on 2026-08-20."],"contexts":[{"id":"disorder:Congenital_Glaucoma","name":"Congenital Glaucoma","kind":"Disorder","source_path":"kb/disorders/Congenital_Glaucoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Congenital_Glaucoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Congenital_Glaucoma.html#dataset-geo-gse272589"}],"context_names":["Congenital Glaucoma"],"disease_names":["Congenital Glaucoma"],"disease_name":"Congenital Glaucoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Congenital_Glaucoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Congenital_Glaucoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Congenital_Glaucoma.html#dataset-geo-gse272589"]},{"id":"dataset:geo:gse272656","accession":"geo:GSE272656","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE272656","title":"VGLL-fusions define a new class of intraparenchymal CNS schwannoma","alternate_titles":[],"description":"This study is important as it identifies and characterizes a new class of benign CNS tumors, termed VGLL-altered intraparenchymal CNS schwannomas. These rare tumors, previously unclassified, resemble schwannomas but are found within CNS tissue. By analyzing 20 tumor samples using advanced molecular and histological techniques, the study reveals that these tumors have a distinct DNA methylation profile and frequently harbor VGLL3 or VGLL1 gene fusions. The findings offer a clearer understanding of their morphology, molecular characteristics, and behavior, with MRI showing well-defined, nodular tumors and clinical data indicating no recurrence during follow-up.","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[24],"sample_count":24,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39713960"],"publication_contexts":[{"context_id":"disorder:Schwannoma","publication":"PMID:39713960"}],"publication":"PMID:39713960","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39713960","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Schwannoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Schwannoma","name":"Schwannoma","kind":"Disorder","source_path":"kb/disorders/Schwannoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Schwannoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Schwannoma.html#dataset-geo-gse272656"}],"context_names":["Schwannoma"],"disease_names":["Schwannoma"],"disease_name":"Schwannoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Schwannoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Schwannoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Schwannoma.html#dataset-geo-gse272656"]},{"id":"dataset:geo:gse272767","accession":"geo:GSE272767","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE272767","title":"Modular small RNA drives the emergence of virulence traits and environmental trade-offs in Vibrio cholerae [Biofilm, AKI]","alternate_titles":[],"description":"The sole gain of laterally acquired virulence genes does not fully explain the transition of environmental strains into human pathogens. To date, the specific molecular drivers and fitness trade-offs that enable some strains within a population to undergo this process remain enigmatic. Here, we describe a small RNA (sRNA) with a unique modular structure that shapes the evolution of toxigenic Vibrio cholerae, the agent of cholera. The sRNA comprises of a highly variable 5’ module located within the ompU ORF and a conserved 3’ one downstream from the gene.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[34],"sample_count":34,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Cholera (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Cholera","name":"Cholera","kind":"Disorder","source_path":"kb/disorders/Cholera.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cholera.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cholera.html#dataset-geo-gse272767"}],"context_names":["Cholera"],"disease_names":["Cholera"],"disease_name":"Cholera","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cholera.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cholera.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cholera.html#dataset-geo-gse272767"]},{"id":"dataset:geo:gse272816","accession":"geo:GSE272816","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE272816","title":"POISONING OF HEALTHY HEMATOPOIESIS IS AN UNANTICIPATED MECHANISM DRIVING CLONAL DOMINANCE IN VEXAS SYNDROME [scRNA-seq]","alternate_titles":[],"description":"Clonal dominance characterizes hematopoiesis during aging and increases susceptibility to blood cancers and common non-malignant disorders. VEXAS syndrome is a recently discovered adult-onset autoinflammatory disease burdened by a high mortality rate and caused by dominant hematopoietic clones bearing somatic mutations in the UBA1 gene. However, pathogenic mechanisms fueling clonal dominance are unknown. Moreover, the lack of disease models hampers the development of disease-modifying therapies. Here, we performed immunophenotypic dissection of hematopoiesis and single-cell transcriptomics in a VEXAS patient cohort revealing pervasive inflammation across all lineages.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[14],"sample_count":14,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40195449"],"publication_contexts":[{"context_id":"disorder:VEXAS_Syndrome","publication":"PMID:40195449"}],"publication":"PMID:40195449","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40195449","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for VEXAS Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:VEXAS_Syndrome","name":"VEXAS Syndrome","kind":"Disorder","source_path":"kb/disorders/VEXAS_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/VEXAS_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/VEXAS_Syndrome.html#dataset-geo-gse272816"}],"context_names":["VEXAS Syndrome"],"disease_names":["VEXAS Syndrome"],"disease_name":"VEXAS Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/VEXAS_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/VEXAS_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/VEXAS_Syndrome.html#dataset-geo-gse272816"]},{"id":"dataset:geo:gse272832","accession":"geo:GSE272832","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE272832","title":"Study on peripheral blood methylation and transcriptome in patients with Graves' disease and Graves' ophthalmopathy","alternate_titles":[],"description":"By studying the differences in transcriptional and methylation levels between the GO (Graves' ophthalmopathy) patient group and the GH (Graves' hyperthyroidism) patient group, we aim to explore the pathogenic mechanisms of GO in patients with GH, and provide intervention guidance for the prevention of GO.","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[54],"sample_count":54,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40215267"],"publication_contexts":[{"context_id":"disorder:Graves_Disease","publication":"PMID:40215267"}],"publication":"PMID:40215267","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40215267","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Graves' Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Graves_Disease","name":"Graves' Disease","kind":"Disorder","source_path":"kb/disorders/Graves_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Graves_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Graves'_Disease.html#dataset-geo-gse272832"}],"context_names":["Graves' Disease"],"disease_names":["Graves' Disease"],"disease_name":"Graves' Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Graves_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Graves_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Graves'_Disease.html#dataset-geo-gse272832"]},{"id":"dataset:geo:gse272904","accession":"geo:GSE272904","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE272904","title":"Emergence of inflammatory fibroblasts with aging in Hermansky-Pudlak syndrome associated pulmonary fibrosis","alternate_titles":[],"description":"The longitudinal cellular interactions that drive pulmonary fibrosis are not well understood. To investigate the disease underpinnings associated with fibrosis onset and progression, we generated a scRNAseq atlas of lungs from young and aged mouse models of multiple subtypes of Hermansky-Pudlak syndrome (HPS), a collection of rare autosomal recessive diseases associated with albinism, platelet dysfunction, and pulmonary fibrosis. We identified an age-dependent increase in SAA3+ inflammatory lung fibroblasts in HPS mice, including in double-mutant HPS1-2 mice which develop spontaneous fibrosis.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[23],"sample_count":23,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39987372"],"publication_contexts":[{"context_id":"disorder:Hermansky_Pudlak_Syndrome","publication":"PMID:39987372"}],"publication":"PMID:39987372","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39987372","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Hermansky-Pudlak Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Hermansky_Pudlak_Syndrome","name":"Hermansky-Pudlak Syndrome","kind":"Disorder","source_path":"kb/disorders/Hermansky_Pudlak_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hermansky_Pudlak_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hermansky-Pudlak_Syndrome.html#dataset-geo-gse272904"}],"context_names":["Hermansky-Pudlak Syndrome"],"disease_names":["Hermansky-Pudlak Syndrome"],"disease_name":"Hermansky-Pudlak Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hermansky_Pudlak_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hermansky_Pudlak_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hermansky-Pudlak_Syndrome.html#dataset-geo-gse272904"]},{"id":"dataset:geo:gse272947","accession":"geo:GSE272947","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE272947","title":"Methylation profiling by array for Dementia with Lewy Bodies using brain tissue","alternate_titles":[],"description":"Synucleinopathies encompass Parkinson's disease (PD), dementia with Lewy bodies (DLB), and Parkinson's disease dementia (PDD) and are recognized for presenting a range of cognitive, neuropsychiatric, sleep-related, motor, and autonomic symptoms. DLB manifests with early-onset dementia when Lewy bodies develop in the brainstem and cerebral cortex. We profiled the DNA methylation using the post-mortem brain tissue from the parietal cortex, specifically Brodmann area 7 and compared them with age-, and sex-matched controls. Through the integration of multi-omics approaches, we anticipate the identification of notable alterations in these well-defined samples.","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[31],"sample_count":31,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39736077"],"publication_contexts":[{"context_id":"disorder:Dementia_with_Lewy_Bodies","publication":"PMID:39736077"}],"publication":"PMID:39736077","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39736077","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Dementia with Lewy Bodies (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Dementia_with_Lewy_Bodies","name":"Dementia with Lewy Bodies","kind":"Disorder","source_path":"kb/disorders/Dementia_with_Lewy_Bodies.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dementia_with_Lewy_Bodies.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Dementia_with_Lewy_Bodies.html#dataset-geo-gse272947"}],"context_names":["Dementia with Lewy Bodies"],"disease_names":["Dementia with Lewy Bodies"],"disease_name":"Dementia with Lewy Bodies","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Dementia_with_Lewy_Bodies.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dementia_with_Lewy_Bodies.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Dementia_with_Lewy_Bodies.html#dataset-geo-gse272947"]},{"id":"dataset:geo:gse273095","accession":"geo:GSE273095","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE273095","title":"Decades-long elevation of interferon-alpha can initiate and drive Sjogren syndrome I","alternate_titles":[],"description":"Sjogren syndrome (SS) is a chronic inflammatory disease with no effective targeted treatments. There is a pressing need to identify targetable pathways which drive disease. Here we combine ultrasensitive detection of IFN-α with proteomic approaches in two cohorts including UK Biobank to demonstrate that IFN-α is elevated in the majority of individuals with SS, and this elevation can precede diagnosis by 15 years and persists for 30 years. We identify a distinct immunological phenotype associated with elevated IFN-α characterised by peripheral blood cytopenias, hypergammaglobulinaemia and SS-specific autoantibody formation.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[8],"sample_count":8,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Sjogren's Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Sjogrens_Syndrome","name":"Sjogren's Syndrome","kind":"Disorder","source_path":"kb/disorders/Sjogrens_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sjogrens_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Sjogren's_Syndrome.html#dataset-geo-gse273095"}],"context_names":["Sjogren's Syndrome"],"disease_names":["Sjogren's Syndrome"],"disease_name":"Sjogren's Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Sjogrens_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sjogrens_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Sjogren's_Syndrome.html#dataset-geo-gse273095"]},{"id":"dataset:geo:gse273098","accession":"geo:GSE273098","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE273098","title":"Decades-long elevation of interferon-alpha can initiate and drive Sjogren syndrome II","alternate_titles":[],"description":"Sjogren syndrome (SS) is a chronic inflammatory disease with no effective targeted treatments. There is a pressing need to identify targetable pathways which drive disease. Here we combine ultrasensitive detection of IFN-α with proteomic approaches in two cohorts including UK Biobank to demonstrate that IFN-α is elevated in the majority of individuals with SS, and this elevation can precede diagnosis by 15 years and persists for 30 years. We identify a distinct immunological phenotype associated with elevated IFN-α characterised by peripheral blood cytopenias, hypergammaglobulinaemia and SS-specific autoantibody formation.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[9],"sample_count":9,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Sjogren's Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Sjogrens_Syndrome","name":"Sjogren's Syndrome","kind":"Disorder","source_path":"kb/disorders/Sjogrens_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sjogrens_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Sjogren's_Syndrome.html#dataset-geo-gse273098"}],"context_names":["Sjogren's Syndrome"],"disease_names":["Sjogren's Syndrome"],"disease_name":"Sjogren's Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Sjogrens_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sjogrens_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Sjogren's_Syndrome.html#dataset-geo-gse273098"]},{"id":"dataset:geo:gse273529","accession":"geo:GSE273529","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE273529","title":"Varicella-zoster virus hijacks the type I interferon response and antigen presentation pathways in matured hiPSC-derived neurospheroids","alternate_titles":[],"description":"NanoString nCounter immune profiling (targeted hybridization-based digital counting; currently mapped to MICROARRAY because schema data_type lacks a targeted expression/NanoString category) of VZV-infected vs Sendai virus-infected hiPSC-derived neurospheroids. Demonstrates that VZV actively suppresses type I interferon signaling and antigen presentation pathways in a CNS-like environment, while Sendai virus triggers robust antiviral responses.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"CL:0000540","label":"neuron","display_label":"neuron","url":"http://purl.obolibrary.org/obo/CL_0000540"}],"sample_type_labels":["neuron"],"sample_counts":[12],"sample_count":12,"conditions":["VZV-infected neurospheroids","Sendai virus-infected neurospheroids","mock-infected controls"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["NanoString nCounter (585 immune transcripts)"],"platform":"NanoString nCounter (585 immune transcripts)","publications":["PMID:39351233"],"publication_contexts":[{"context_id":"disorder:Chickenpox","publication":"PMID:39351233"}],"publication":"PMID:39351233","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39351233","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Directly relevant to VZV immune evasion pathophysiology. Shows VZV suppresses innate immunity in neurons, supporting the latency establishment mechanism. cell_type_term uses neuron to represent the predominant infected cell population within the neurospheroid model."],"contexts":[{"id":"disorder:Chickenpox","name":"Chickenpox","kind":"Disorder","source_path":"kb/disorders/Chickenpox.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chickenpox.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chickenpox.html#dataset-geo-gse273529"}],"context_names":["Chickenpox"],"disease_names":["Chickenpox"],"disease_name":"Chickenpox","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chickenpox.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chickenpox.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chickenpox.html#dataset-geo-gse273529"]},{"id":"dataset:geo:gse273559","accession":"geo:GSE273559","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE273559","title":"Single-cell profiling of prurigo nodularis demonstrates immune-stromal crosstalk driving profibrotic responses and reversal with nemolizumab","alternate_titles":[],"description":"Prurigo nodularis (PN) is a chronic neuroimmune skin disease characterized by bilaterally distributed pruritic hyperkeratotic nodules on extremities and trunk. Neuroimmune dysregulation and chronic scratching are believed to both induce and maintain the characteristic lesions. This study sought to provide a comprehensive view of the molecular pathogenesis of PN at the single-cell level to identify and outline key pathologic processes and the cell types involved. Features that distinguish PN skin from the skin of patients with atopic dermatitis were of particular interest.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:37506977"],"publication_contexts":[{"context_id":"disorder:Prurigo_Nodularis","publication":"PMID:37506977"}],"publication":"PMID:37506977","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/37506977","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Prurigo Nodularis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Prurigo_Nodularis","name":"Prurigo Nodularis","kind":"Disorder","source_path":"kb/disorders/Prurigo_Nodularis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Prurigo_Nodularis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Prurigo_Nodularis.html#dataset-geo-gse273559"}],"context_names":["Prurigo Nodularis"],"disease_names":["Prurigo Nodularis"],"disease_name":"Prurigo Nodularis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Prurigo_Nodularis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Prurigo_Nodularis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Prurigo_Nodularis.html#dataset-geo-gse273559"]},{"id":"dataset:geo:gse273571","accession":"geo:GSE273571","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE273571","title":"JAK-STAT1 as therapeutic target for EGFR deficiency-associated inflammation and scarring alopecia (RNA-seq of HFSC)","alternate_titles":[],"description":"Bulk RNA-seq of mouse hair follicle stem cells from EGFR-deficient versus wild-type conditions in a model used to study chronic folliculitis and scarring alopecia.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"house mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":["hair follicle stem cells, EGFR-deficient model","hair follicle stem cells, wild type"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39521937"],"publication_contexts":[{"context_id":"disorder:Folliculitis","publication":"PMID:39521937"}],"publication":"PMID:39521937","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39521937","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE273571","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE273571","reference_title":"JAK-STAT1 as therapeutic target for EGFR deficiency-associated inflammation and scarring alopecia (RNA-seq of HFSC)","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"Mechanistically, disruption of EGFR signalling generated a cell-intrinsic hypersensitivity within the JAK-STAT1 pathway, which, synergistically with interferon gamma expressing CD8 T-cell and NK-cell-mediated inflammation, compromised the stem cell niche.","explanation":"Supports mechanistic transcriptomic interrogation of EGFR-driven follicular inflammatory injury."},{"reference":"GEO:GSE273571","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE273571","reference_title":"JAK-STAT1 as therapeutic target for EGFR deficiency-associated inflammation and scarring alopecia (RNA-seq of HFSC)","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"Our findings offer molecular insights and present a mechanism-based therapeutic strategy for addressing chronic folliculitis associated with EGFR-inhibitor anti-cancer therapy and cicatricial alopecia.","explanation":"Explicitly links this dataset context to chronic folliculitis biology."}],"notes":[],"contexts":[{"id":"disorder:Folliculitis","name":"Folliculitis","kind":"Disorder","source_path":"kb/disorders/Folliculitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Folliculitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Folliculitis.html#dataset-geo-gse273571"}],"context_names":["Folliculitis"],"disease_names":["Folliculitis"],"disease_name":"Folliculitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Folliculitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Folliculitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Folliculitis.html#dataset-geo-gse273571"]},{"id":"dataset:geo:gse273572","accession":"geo:GSE273572","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE273572","title":"JAK-STAT1 as therapeutic target for EGFR deficiency-associated inflammation and scarring alopecia (scRNA-seq)","alternate_titles":[],"description":"Single-cell RNA-seq of EGFR-deficient mouse epidermal context generated to characterize follicular immune-epithelial dysregulation in scarring folliculitis biology.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"house mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[1],"sample_count":1,"conditions":["EGFR-deficient epidermal context"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39521937"],"publication_contexts":[{"context_id":"disorder:Folliculitis","publication":"PMID:39521937"}],"publication":"PMID:39521937","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39521937","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE273572","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE273572","reference_title":"JAK-STAT1 as therapeutic target for EGFR deficiency-associated inflammation and scarring alopecia (scRNA-seq)","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"In this study, we demonstrated the protective role of hair follicle-specific epidermal growth factor receptor (EGFR) against scarring hair follicle destruction.","explanation":"Supports the dataset's central focus on follicle-protective EGFR signaling in a scarring folliculitis model."},{"reference":"GEO:GSE273572","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE273572","reference_title":"JAK-STAT1 as therapeutic target for EGFR deficiency-associated inflammation and scarring alopecia (scRNA-seq)","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"Notably, a case study of folliculitis decalvans, characterized by progressive hair loss, scaling and perifollicular erythema, demonstrated successful treatment with JAK1/2 inhibition.","explanation":"Provides direct folliculitis decalvans clinical linkage for interpretation of model-derived single-cell signatures."}],"notes":[],"contexts":[{"id":"disorder:Folliculitis","name":"Folliculitis","kind":"Disorder","source_path":"kb/disorders/Folliculitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Folliculitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Folliculitis.html#dataset-geo-gse273572"}],"context_names":["Folliculitis"],"disease_names":["Folliculitis"],"disease_name":"Folliculitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Folliculitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Folliculitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Folliculitis.html#dataset-geo-gse273572"]},{"id":"dataset:geo:gse273720","accession":"geo:GSE273720","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE273720","title":"ICI-SJS/TEN mediated by macrophage-derived CXCL10 and abated by TNF blockade","alternate_titles":[],"description":"Immune checkpoint inhibitors (ICI) represent new anticancer agents and have been used worldwide. However, ICI can potentially induce life-threatening severe cutaneous adverse reaction (SCAR), such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), hindering continuous ICI therapy. We examined 6 cohorts within 25 ICI-induced SJS/TEN patients and conducted single-cell RNA sequencing (scRNA-seq) analysis, which revealed overexpression of macrophage-derived CXCL10 that recruited CXCR3+ cytotoxic T lymphocytes (CTL) in blister cells from ICI-SJS/TEN skin lesions.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[46],"sample_count":46,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39737932"],"publication_contexts":[{"context_id":"disorder:Stevens-Johnson_Syndrome","publication":"PMID:39737932"}],"publication":"PMID:39737932","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39737932","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Stevens-Johnson Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Stevens-Johnson_Syndrome","name":"Stevens-Johnson Syndrome","kind":"Disorder","source_path":"kb/disorders/Stevens-Johnson_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Stevens-Johnson_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Stevens-Johnson_Syndrome.html#dataset-geo-gse273720"}],"context_names":["Stevens-Johnson Syndrome"],"disease_names":["Stevens-Johnson Syndrome"],"disease_name":"Stevens-Johnson Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Stevens-Johnson_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Stevens-Johnson_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Stevens-Johnson_Syndrome.html#dataset-geo-gse273720"]},{"id":"dataset:geo:gse273805","accession":"geo:GSE273805","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE273805","title":"TNF Superfamily Member 14 Drives Post-Influenza Depletion of Alveolar  Macrophages Enabling Secondary Pneumococcal Pneumonia","alternate_titles":[],"description":"Secondary bacterial infection, often caused by Streptococcus pneumoniae (Spn), is one of the most frequent and severe complications of influenza A virus (IAV)-induced pneumonia. Phenotyping of the pulmonary innate immune landscape after IAV infection revealed a significant depletion of the tissue-resident alveolar macrophage (TR-AM) population at day 7, which was associated with increased susceptibility to Spn outgrowth. To elucidate the molecular mechanisms underlying TR-AM depletion, and to define putative targets for treatment, we combined single-cell transcriptomics and cell-specific PCR profiling in an unbiased manner, using in vivo models of IAV infection and IAV/Spn co-infection.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[7],"sample_count":7,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41252214"],"publication_contexts":[{"context_id":"disorder:Pneumococcal_Pneumonia","publication":"PMID:41252214"}],"publication":"PMID:41252214","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41252214","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Pneumococcal Pneumonia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Pneumococcal_Pneumonia","name":"Pneumococcal Pneumonia","kind":"Disorder","source_path":"kb/disorders/Pneumococcal_Pneumonia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pneumococcal_Pneumonia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pneumococcal_Pneumonia.html#dataset-geo-gse273805"}],"context_names":["Pneumococcal Pneumonia"],"disease_names":["Pneumococcal Pneumonia"],"disease_name":"Pneumococcal Pneumonia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Pneumococcal_Pneumonia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pneumococcal_Pneumonia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Pneumococcal_Pneumonia.html#dataset-geo-gse273805"]},{"id":"dataset:geo:gse274124","accession":"geo:GSE274124","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE274124","title":"Transcriptome analysis of patient derived induced pluripotent stem cell derived cardiomyocytes with severe, early onset hypertrophic cardiomyopathy due to biallelic MYBPC3 variants c.442G>A and c.506-1G>A","alternate_titles":[],"description":"Transcriptomes of cardiomyocytes derived from a patient carrying two MYBPC3 variants in trans with severe early-onset disease, against a healthy control line. The closest available omics resource to the LVNC10 genotype in human cells, though not an exact match: one allele is a splice variant and the other is annotated low-penetrance pathogenic, so this is a biallelic genotype but not the truncating/truncating configuration the biallelic subtype is defined by.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:7551","label":"MYBPC3","display_label":"MYBPC3","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/7551"}],"genes":["MYBPC3"],"platforms":[],"platform":null,"publications":["PMID:39633578"],"publication_contexts":[{"context_id":"disorder:Left_Ventricular_Noncompaction_10","publication":"PMID:39633578"}],"publication":"PMID:39633578","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39633578","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE274124","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE274124","reference_title":"Transcriptome analysis of patient derived induced pluripotent stem cell derived cardiomyocytes with severe, early onset hypertrophic cardiomyopathy due to biallelic MYBPC3 variants c.442G>A and c.506-1G>A","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Induced pluripotent stem cells (iPSCs) were generated from a patient with severe, early onset hypertrophic cardiomyopathy due to pathogenic (c.506-1G>A) and low penetrance pathogenic (c.442G>A) variants in MYBPC3 in trans (i.e. MYBPC3 biallelic patient).","explanation":"The GEO summary establishes the biallelic in-trans genotype and the severe early-onset presentation, which is why this dataset is curated here rather than under the heterozygous CMH4 entry."}],"notes":["The patient's phenotype is recorded as hypertrophic, not noncompaction, and the allele pair is splice-plus-low-penetrance-missense rather than two truncating alleles. Curated for the biallelic configuration and the early-onset severity, which are what this entry models; it is not a noncompaction dataset, and no omics resource keyed to the LVNC10 phenotype itself was found."],"contexts":[{"id":"disorder:Left_Ventricular_Noncompaction_10","name":"Left Ventricular Noncompaction 10","kind":"Disorder","source_path":"kb/disorders/Left_Ventricular_Noncompaction_10.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Left_Ventricular_Noncompaction_10.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Left_Ventricular_Noncompaction_10.html#dataset-geo-gse274124"}],"context_names":["Left Ventricular Noncompaction 10"],"disease_names":["Left Ventricular Noncompaction 10"],"disease_name":"Left Ventricular Noncompaction 10","same_context_model_ids":["model:kb/disorders/Left_Ventricular_Noncompaction_10.yaml:Biallelic MYBPC3 truncating hiPSC line with isogenic control","model:kb/disorders/Left_Ventricular_Noncompaction_10.yaml:Isogenic hiPSC-cardiomyocytes carrying MYBPC3 premature termination codon variants"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Left_Ventricular_Noncompaction_10.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Left_Ventricular_Noncompaction_10.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Left_Ventricular_Noncompaction_10.html#dataset-geo-gse274124"]},{"id":"dataset:geo:gse274298","accession":"geo:GSE274298","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE274298","title":"SMPDL3b in Podocytes: Decoupling Proteinuria from CKD Progression in Experimental Alport Syndrome","alternate_titles":[],"description":"Alport Syndrome (AS) is a rare genetic disease with impaired production of collagen type IV alpha 3, 4 and 5 chains in the glomerular basement membranes (GBM), which results amongst others in progressive loss of kidney function. In AS, abnormalities in the GBM and associated podocyte detachment may potentially result from the dysregulation of sphingolipid metabolism. Here we investigated whether renal sphingomyelin phosphodiesterase acid-like 3b (SMPDL3b) overexpression modulates the generation of sphingosine-1-phosphate (S1P) and contributes to renal failure in Col4a3 knockout mice, a mouse model of AS.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39684843"],"publication_contexts":[{"context_id":"disorder:Alport_Syndrome","publication":"PMID:39684843"}],"publication":"PMID:39684843","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39684843","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Alport Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Alport_Syndrome","name":"Alport Syndrome","kind":"Disorder","source_path":"kb/disorders/Alport_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alport_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Alport_Syndrome.html#dataset-geo-gse274298"}],"context_names":["Alport Syndrome"],"disease_names":["Alport Syndrome"],"disease_name":"Alport Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Alport_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alport_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Alport_Syndrome.html#dataset-geo-gse274298"]},{"id":"dataset:geo:gse274660","accession":"geo:GSE274660","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE274660","title":"Epigenetic insights into GABAergic development in Dravet Syndrome iPSC and therapeutic implications","alternate_titles":[],"description":"Dravet syndrome (DS) is a devastating early onset refractory epilepsy syndrome caused by variants in the SCN1A gene. A disturbed GABAergic interneuron function is implicated in the progression to DS but the underlying developmental and pathophysiological mechanisms remain elusive, in particularly at the chromatin level. In this study, we utilized induced pluripotent stem cells (iPSCs) derived from DS cases and healthy donors to model disease-associated epigenetic abnormalities of GABAergic development. Employing the ATAC-Seq technique, we assessed chromatin accessibility at multiple time points (Day 0, Day 19, Day 35, and Day 65) of GABAergic differentiation.","alternate_descriptions":[],"data_types":["ATAC_SEQ"],"data_type_labels":["Assay for transposase-accessible chromatin sequencing"],"data_type_label":"Assay for transposase-accessible chromatin sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[56],"sample_count":56,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Dravet syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Dravet_syndrome","name":"Dravet_syndrome","kind":"Disorder","source_path":"kb/disorders/Dravet_syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dravet_syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Dravet_syndrome.html#dataset-geo-gse274660"}],"context_names":["Dravet_syndrome"],"disease_names":["Dravet_syndrome"],"disease_name":"Dravet_syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Dravet_syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dravet_syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Dravet_syndrome.html#dataset-geo-gse274660"]},{"id":"dataset:geo:gse274766","accession":"geo:GSE274766","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE274766","title":"scRNA-seq time-course of Coccidioides posadasii infected lungs","alternate_titles":[],"description":"Single-cell RNA-seq time course of murine lung during Coccidioides posadasii infection, comparing uninfected lung (D0) with infected lung at 5, 9, and 14 days post-infection. Resolves the cellular composition of the pulmonary response over the interval in which containment is established or lost.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"house mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[1],"sample_count":1,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39611685"],"publication_contexts":[{"context_id":"disorder:Coccidioidomycosis","publication":"PMID:39611685"}],"publication":"PMID:39611685","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39611685","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Coccidioidomycosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities. Title, sample count, and organism are GEO's own values. No evidence block: bulk-discovered dataset records carry repository provenance rather than a quoted abstract."],"contexts":[{"id":"disorder:Coccidioidomycosis","name":"Coccidioidomycosis","kind":"Disorder","source_path":"kb/disorders/Coccidioidomycosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Coccidioidomycosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Coccidioidomycosis.html#dataset-geo-gse274766"}],"context_names":["Coccidioidomycosis"],"disease_names":["Coccidioidomycosis"],"disease_name":"Coccidioidomycosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Coccidioidomycosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Coccidioidomycosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Coccidioidomycosis.html#dataset-geo-gse274766"]},{"id":"dataset:geo:gse274767","accession":"geo:GSE274767","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE274767","title":"Spatial Transcriptomics of Lungs Infected with Coccidioides posadasii","alternate_titles":[],"description":"10x Visium spatial transcriptomics of murine lung, comparing non-infected lung (D0) with lung at 14 days post-infection with Coccidioides posadasii. Spatially resolved counterpart to GSE274766 from the same study, relevant to the organization of the granulomatous lesion.","alternate_descriptions":[],"data_types":["SPATIAL_TRANSCRIPTOMICS"],"data_type_labels":["Spatially resolved transcriptomics"],"data_type_label":"Spatially resolved transcriptomics","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"house mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[2],"sample_count":2,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39611685"],"publication_contexts":[{"context_id":"disorder:Coccidioidomycosis","publication":"PMID:39611685"}],"publication":"PMID:39611685","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39611685","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Coccidioidomycosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Coccidioidomycosis","name":"Coccidioidomycosis","kind":"Disorder","source_path":"kb/disorders/Coccidioidomycosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Coccidioidomycosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Coccidioidomycosis.html#dataset-geo-gse274767"}],"context_names":["Coccidioidomycosis"],"disease_names":["Coccidioidomycosis"],"disease_name":"Coccidioidomycosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Coccidioidomycosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Coccidioidomycosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Coccidioidomycosis.html#dataset-geo-gse274767"]},{"id":"dataset:geo:gse274795","accession":"geo:GSE274795","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE274795","title":"Unveiling the molecular landscape of dental caries and its impact on ECM remodeling","alternate_titles":[],"description":"The rapid progression of caries lesions in dentin is facilitated by its reduced mineralization, high organic content, and tubular structure, contributing to ECM degradation through MMP activation in acidic conditions. This study investigates the expression of collagenases (MMP-2 and MMP-9) and their inhibitors (TIMP-1 and TIMP-2) in the pulp, predentin, and dentin of decayed teeth. RNA from these tissues was sequenced using Illumina® technology. Quality validation, read alignment to the human transcriptome, and differential gene expression analysis were performed. Gene Ontology and KEGG pathway analyses identified significant biological processes.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Dental Caries (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Dental_Caries","name":"Dental Caries","kind":"Disorder","source_path":"kb/disorders/Dental_Caries.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dental_Caries.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Dental_Caries.html#dataset-geo-gse274795"}],"context_names":["Dental Caries"],"disease_names":["Dental Caries"],"disease_name":"Dental Caries","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Dental_Caries.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dental_Caries.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Dental_Caries.html#dataset-geo-gse274795"]},{"id":"dataset:geo:gse275048","accession":"geo:GSE275048","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE275048","title":"The CoREST complex is a therapeutic vulnerability in malignant peripheral nerve sheath tumors (RNA-Seq)","alternate_titles":[],"description":"Malignant peripheral nerve sheath tumor (MPNST) is a highly aggressive sarcoma that may be seen in patients with neurofibromatosis type 1 (NF1) or occur sporadically. While surgery is the primary treatment for localized MPNST with a 61.9% overall survival rate, metastatic disease is often fatal due to resistance to systemic therapies which underscores the urgent need for effective treatments. MPNSTs frequently harbor inactivating driver mutations in the PRC2 epigenetic repressor complex suggesting epigenetic therapies may represent a specific vulnerability in these tumors.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[16],"sample_count":16,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40128216"],"publication_contexts":[{"context_id":"disorder:Malignant_Peripheral_Nerve_Sheath_Tumor","publication":"PMID:40128216"}],"publication":"PMID:40128216","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40128216","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Malignant Peripheral Nerve Sheath Tumor (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Malignant_Peripheral_Nerve_Sheath_Tumor","name":"Malignant Peripheral Nerve Sheath Tumor","kind":"Disorder","source_path":"kb/disorders/Malignant_Peripheral_Nerve_Sheath_Tumor.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Malignant_Peripheral_Nerve_Sheath_Tumor.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Malignant_Peripheral_Nerve_Sheath_Tumor.html#dataset-geo-gse275048"}],"context_names":["Malignant Peripheral Nerve Sheath Tumor"],"disease_names":["Malignant Peripheral Nerve Sheath Tumor"],"disease_name":"Malignant Peripheral Nerve Sheath Tumor","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Malignant_Peripheral_Nerve_Sheath_Tumor.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Malignant_Peripheral_Nerve_Sheath_Tumor.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Malignant_Peripheral_Nerve_Sheath_Tumor.html#dataset-geo-gse275048"]},{"id":"dataset:geo:gse275370","accession":"geo:GSE275370","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE275370","title":"Multicellular derived S100A8/A9 maintains megakaryocytes in an immature state in immune thrombocytopenia.","alternate_titles":[],"description":"Immune thrombocytopenia (ITP) is a common acquired autoimmune bleeding disorder characterized by reduced platelet count. Impaired maturation of megakaryocyte (MK) plays an important role, although the exact mechanisms are not fully understood. In this study, we performed 10x Genomics single-cell sequencing (SC-seq) on bone marrow samples from ITP patients and validated the data through in vitro models of megakaryocyte generation.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[7],"sample_count":7,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41414965"],"publication_contexts":[{"context_id":"disorder:Immune_Thrombocytopenia","publication":"PMID:41414965"}],"publication":"PMID:41414965","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41414965","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Immune Thrombocytopenia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Immune_Thrombocytopenia","name":"Immune Thrombocytopenia","kind":"Disorder","source_path":"kb/disorders/Immune_Thrombocytopenia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Immune_Thrombocytopenia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Immune_Thrombocytopenia.html#dataset-geo-gse275370"}],"context_names":["Immune Thrombocytopenia"],"disease_names":["Immune Thrombocytopenia"],"disease_name":"Immune Thrombocytopenia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Immune_Thrombocytopenia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Immune_Thrombocytopenia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Immune_Thrombocytopenia.html#dataset-geo-gse275370"]},{"id":"dataset:geo:gse27545","accession":"geo:GSE27545","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE27545","title":"A Systems Approach for Decoding Mitochondrial Retrograde Signaling Pathways","alternate_titles":[],"description":"Expression profiling of cells engineered to carry varying amounts of m.3243A>G, used to infer the transcription factors mediating mitochondrial retrograde signalling; identifies an RXRA-ROS-JNK-PGC1alpha loop that further suppresses nuclear-encoded OXPHOS genes.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[17],"sample_count":17,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:23443683"],"publication_contexts":[{"context_id":"disorder:MELAS_Syndrome","publication":"PMID:23443683"}],"publication":"PMID:23443683","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/23443683","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:23443683","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/23443683","reference_title":"A systems approach for decoding mitochondrial retrograde signaling pathways.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"This RXR pathway contributed to the decrease in mRNA abundances of oxidative phosphorylation enzymes encoded in the nuclear genome, thereby aggravating the dysfunction in oxidative phosphorylation caused by the reduced abundance of mitochondria-encoded enzymes of oxidative phosphorylation.","explanation":"Describes a self-aggravating retrograde loop, a candidate mechanism for progression from a non-progressive genetic lesion."}],"notes":["Supplies a candidate feed-forward mechanism by which a fixed mtDNA lesion progressively worsens nuclear OXPHOS gene expression, which is one of the few published proposals for why MELAS is progressive rather than static."],"contexts":[{"id":"disorder:MELAS_Syndrome","name":"MELAS Syndrome","kind":"Disorder","source_path":"kb/disorders/MELAS_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MELAS_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/MELAS_Syndrome.html#dataset-geo-gse27545"}],"context_names":["MELAS Syndrome"],"disease_names":["MELAS Syndrome"],"disease_name":"MELAS Syndrome","same_context_model_ids":["model:kb/disorders/MELAS_Syndrome.yaml:m.3243A>G patient iPSC-derived neurons"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/MELAS_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MELAS_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/MELAS_Syndrome.html#dataset-geo-gse27545"]},{"id":"dataset:geo:gse275494","accession":"geo:GSE275494","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE275494","title":"Non-canonical roles of CFH in retinal pigment epithelial cells revealed by dysfunctional rare CFH variants","alternate_titles":[],"description":"Complement Factor H (CFH) common genetic variants have been associated with age-related macular degeneration (AMD). While most previous in vitro RPE studies focused on the common p.His402Tyr CFH variant, we characterized rare CFH variants that are highly penetrant for AMD using induced pluripotent stem cell derived retinal pigment epithelium (iPSC-RPE). Our results show that lower FH levels were detected in AMD RPE, which potentially disrupted canonical and non-canonical roles of FH. Specifically, AMD RPE displayed higher inflammation rate and a reduced set of differentially expressed genes compared to control RPE upon A2E and blue light challenge.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[90],"sample_count":90,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39753135"],"publication_contexts":[{"context_id":"disorder:Age_Related_Macular_Degeneration","publication":"PMID:39753135"}],"publication":"PMID:39753135","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39753135","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Age-Related Macular Degeneration (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Age_Related_Macular_Degeneration","name":"Age-Related Macular Degeneration","kind":"Disorder","source_path":"kb/disorders/Age_Related_Macular_Degeneration.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Age_Related_Macular_Degeneration.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Age-Related_Macular_Degeneration.html#dataset-geo-gse275494"}],"context_names":["Age-Related Macular Degeneration"],"disease_names":["Age-Related Macular Degeneration"],"disease_name":"Age-Related Macular Degeneration","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Age_Related_Macular_Degeneration.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Age_Related_Macular_Degeneration.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Age-Related_Macular_Degeneration.html#dataset-geo-gse275494"]},{"id":"dataset:geo:gse275677","accession":"geo:GSE275677","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE275677","title":"RUNX2 as a novel Biomarker for early identification of Patients Progressing to Advanced-Stage Mycosis Fungoides","alternate_titles":[],"description":"Here, we used spatial transcriptomics on skin samples at time-of-diagnosis to enable prediction of patients who later progressed to advanced stages of MF. Formalin-fixed, paraffin-embedded skin biopsies at time of diagnosis from six patients with MF who progressed to advanced stages of disease within 4 months to 12 years after diagnosis, and nine patients who remained in early-stage disease over 9 to 27 years were analyzed using the GeoMx Digital Spatial Profiler to capture spatially resolved high-plex RNA gene expression data.","alternate_descriptions":[],"data_types":["SPATIAL_TRANSCRIPTOMICS"],"data_type_labels":["Spatially resolved transcriptomics"],"data_type_label":"Spatially resolved transcriptomics","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[68],"sample_count":68,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39435287"],"publication_contexts":[{"context_id":"disorder:Mycosis_Fungoides","publication":"PMID:39435287"}],"publication":"PMID:39435287","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39435287","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Mycosis Fungoides (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Mycosis_Fungoides","name":"Mycosis Fungoides","kind":"Disorder","source_path":"kb/disorders/Mycosis_Fungoides.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mycosis_Fungoides.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Mycosis_Fungoides.html#dataset-geo-gse275677"}],"context_names":["Mycosis Fungoides"],"disease_names":["Mycosis Fungoides"],"disease_name":"Mycosis Fungoides","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Mycosis_Fungoides.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mycosis_Fungoides.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Mycosis_Fungoides.html#dataset-geo-gse275677"]},{"id":"dataset:geo:gse275710","accession":"geo:GSE275710","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE275710","title":"MicroRNAs in plasma-derived extracellular vesicles as non-invasive biomarkers for eosinophilic esophagitis","alternate_titles":[],"description":"Background: The lack of non-invasive biomarkers imposes the dependence on endoscopy with biopsies for the diagnosis and monitoring of eosinophilic esophagitis (EoE), a prevalent chronic inflammation of the esophagus mediated by a type 2 immune response. We aimed to identify potential non-invasive biomarkers using microRNAs (miRNAs) in plasma-derived extracellular vesicles (pEVs). Methods: This is a prospective single-center observational study including a discovery cohort of EoE patients (n=26) with active disease (EoE.Basal) and after anti-inflammatory treatment (EoE.Post.tx), and control subjects (n=16).","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[70],"sample_count":70,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39859353"],"publication_contexts":[{"context_id":"disorder:Eosinophilic_Esophagitis","publication":"PMID:39859353"}],"publication":"PMID:39859353","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39859353","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Eosinophilic Esophagitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Eosinophilic_Esophagitis","name":"Eosinophilic Esophagitis","kind":"Disorder","source_path":"kb/disorders/Eosinophilic_Esophagitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Eosinophilic_Esophagitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Eosinophilic_Esophagitis.html#dataset-geo-gse275710"}],"context_names":["Eosinophilic Esophagitis"],"disease_names":["Eosinophilic Esophagitis"],"disease_name":"Eosinophilic Esophagitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Eosinophilic_Esophagitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Eosinophilic_Esophagitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Eosinophilic_Esophagitis.html#dataset-geo-gse275710"]},{"id":"dataset:geo:gse276210","accession":"geo:GSE276210","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE276210","title":"Beta-Adrenergic Stimulation and MYH7 G256E Mutant Gene Dosage Drive Hypertrophic Cardiomyopathy Phenotype Penetrance","alternate_titles":[],"description":"Single-cell RNA sequencing of day-30 iPSC-cardiomyocytes carrying heterozygous MYH7 G256E and H251N, plus homozygous G256E and isoproterenol-treated heterozygotes. 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No evidence block: a bulk-discovered accession has no abstract quote to anchor an evidence item."],"contexts":[{"id":"disorder:Toxoplasmosis","name":"Toxoplasmosis","kind":"Disorder","source_path":"kb/disorders/Toxoplasmosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Toxoplasmosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Toxoplasmosis.html#dataset-geo-gse276786"}],"context_names":["Toxoplasmosis"],"disease_names":["Toxoplasmosis"],"disease_name":"Toxoplasmosis","same_context_model_ids":["model:kb/disorders/Toxoplasmosis.yaml:Human cell culture single-cell transcriptomics of ROP/GRA effector injection","model:kb/disorders/Toxoplasmosis.yaml:Stress-induced bradyzoite differentiation in cell culture"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Toxoplasmosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Toxoplasmosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Toxoplasmosis.html#dataset-geo-gse276786"]},{"id":"dataset:geo:gse276899","accession":"geo:GSE276899","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE276899","title":"Circulating nucleic acids in plasma of individuals with human lymphatic filariasis","alternate_titles":[],"description":"Circulating nucleic acids (RNA / DNA) found in body fluids have been shown to be good biomarkers for diagnosis of infections. 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mechanistic insight into MED13L syndrome."}],"notes":[],"contexts":[{"id":"disorder:Mediator_Complex_Neurodevelopmental_Disorder","name":"Mediator Complex Neurodevelopmental Disorder","kind":"Disorder","source_path":"kb/disorders/Mediator_Complex_Neurodevelopmental_Disorder.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mediator_Complex_Neurodevelopmental_Disorder.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Mediator_Complex_Neurodevelopmental_Disorder.html#dataset-geo-gse277054"}],"context_names":["Mediator Complex Neurodevelopmental Disorder"],"disease_names":["Mediator Complex Neurodevelopmental Disorder"],"disease_name":"Mediator Complex Neurodevelopmental Disorder","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Mediator_Complex_Neurodevelopmental_Disorder.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mediator_Complex_Neurodevelopmental_Disorder.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Mediator_Complex_Neurodevelopmental_Disorder.html#dataset-geo-gse277054"]},{"id":"dataset:geo:gse277340","accession":"geo:GSE277340","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE277340","title":"Transcriptomic Profiling Reveals the Role of Hedgehog Signaling as a Biomarker and in the Pathogenesis of Ménétrier’s Disease","alternate_titles":[],"description":"Human stomach bulk RNA-seq dataset including juvenile polyposis syndrome, Ménétrier's disease, and unaffected stomach samples, generated to define shared versus differential gastric transcriptomic programs and improve diagnostic discrimination.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0000945","label":"stomach","display_label":"stomach tissue","url":"http://purl.obolibrary.org/obo/UBERON_0000945"}],"sample_type_labels":["stomach"],"sample_counts":[9],"sample_count":9,"conditions":["juvenile polyposis syndrome","Ménétrier's disease","unaffected stomach"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41199529"],"publication_contexts":[{"context_id":"disorder:Juvenile_Polyposis_Syndrome","publication":"PMID:41199529"}],"publication":"PMID:41199529","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41199529","publication_status":"Publication recorded","findings":[{"statement":"Gastric transcriptomic profiling distinguishes JPS from Ménétrier's disease while revealing shared estrogen receptor, integrin, and mTOR pathway signatures.","evidence":[{"reference":"PMID:41199529","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41199529","reference_title":"Transcriptomic profiling reveals the role of Hedgehog signaling as a biomarker and in the pathogenesis of Ménétrier's disease.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"Comparative analysis between MD and JPS revealed both common and differential gene signatures.","explanation":"This supports the dataset's value for direct transcriptomic comparison between gastric JPS and Ménétrier's disease."},{"reference":"PMID:41199529","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41199529","reference_title":"Transcriptomic profiling reveals the role of Hedgehog signaling as a biomarker and in the pathogenesis of Ménétrier's disease.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"Common gene signatures included estrogen receptor signaling, integrin signaling, mTOR signaling, and others, which may be responsible for histopathological similarities.","explanation":"This supports the dataset as a resource for pathway-level analysis of shared gastric disease biology in JPS."}]}],"findings_text":["Gastric transcriptomic profiling distinguishes JPS from Ménétrier's disease while revealing shared estrogen receptor, integrin, and mTOR pathway signatures."],"evidence":[{"reference":"PMID:41199529","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41199529","reference_title":"Transcriptomic profiling reveals the role of Hedgehog signaling as a biomarker and in the pathogenesis of Ménétrier's disease.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"To identify diagnostic markers for MD and to better understand the pathogenesis of the disease, we performed transcriptomic profiling of stomach tissues from normal (NL), MD, and JPS patients.","explanation":"This supports inclusion of the GEO series as a JPS-relevant human stomach transcriptomic dataset."},{"reference":"PMID:41199529","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41199529","reference_title":"Transcriptomic profiling reveals the role of Hedgehog signaling as a biomarker and in the pathogenesis of Ménétrier's disease.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"Comparative analysis between MD and JPS revealed both common and differential gene signatures.","explanation":"This supports the dataset's value for direct transcriptomic comparison between gastric JPS and Ménétrier's disease."},{"reference":"PMID:41199529","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41199529","reference_title":"Transcriptomic profiling reveals the role of Hedgehog signaling as a biomarker and in the pathogenesis of Ménétrier's disease.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"Common gene signatures included estrogen receptor signaling, integrin signaling, mTOR signaling, and others, which may be responsible for histopathological similarities.","explanation":"This supports the dataset as a resource for pathway-level analysis of shared gastric disease biology in JPS."}],"notes":[],"contexts":[{"id":"disorder:Juvenile_Polyposis_Syndrome","name":"Juvenile Polyposis Syndrome","kind":"Disorder","source_path":"kb/disorders/Juvenile_Polyposis_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Juvenile_Polyposis_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Juvenile_Polyposis_Syndrome.html#dataset-geo-gse277340"}],"context_names":["Juvenile Polyposis Syndrome"],"disease_names":["Juvenile Polyposis Syndrome"],"disease_name":"Juvenile Polyposis Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Juvenile_Polyposis_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Juvenile_Polyposis_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Juvenile_Polyposis_Syndrome.html#dataset-geo-gse277340"]},{"id":"dataset:geo:gse277596","accession":"geo:GSE277596","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE277596","title":"Dissection of the immune landscape in Psoriatic Arthritis patients","alternate_titles":[],"description":"Despite significant advancements in psoriatic arthritis (PsA) treatment modalities, a considerable proportion of patients continue to experience persistent joint inflammation and functional impairment, unresponsive to the armamentarium of biological disease-modifying antirheumatic drugs (bDMARDs) or Janus kinase (JAK) inhibitors. The etiology of resistance in these cases is complex, likely involving intricate immunological and genetic factors which are currently mostly unknown. Identifying novel biomarkers and targets for refractory disease is urgently needed.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[635],"sample_count":635,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40478933"],"publication_contexts":[{"context_id":"disorder:Psoriatic_Arthritis","publication":"PMID:40478933"}],"publication":"PMID:40478933","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40478933","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Psoriatic Arthritis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Psoriatic_Arthritis","name":"Psoriatic Arthritis","kind":"Disorder","source_path":"kb/disorders/Psoriatic_Arthritis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Psoriatic_Arthritis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Psoriatic_Arthritis.html#dataset-geo-gse277596"}],"context_names":["Psoriatic Arthritis"],"disease_names":["Psoriatic Arthritis"],"disease_name":"Psoriatic Arthritis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Psoriatic_Arthritis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Psoriatic_Arthritis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Psoriatic_Arthritis.html#dataset-geo-gse277596"]},{"id":"dataset:geo:gse277624","accession":"geo:GSE277624","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE277624","title":"CD163+ cardiac macrophages attenuate pressure overload-induced left ventricular systolic dysfunction via interleukin-10","alternate_titles":[],"description":"Background Chronic sustained pressure overload induces cardiac remodeling, which often leads to heart failure. Cardiac macrophages (cMacs) are heterogeneous cell populations, and their elimination has been shown to exacerbate pressure overload-induced heart failure. CD163, a macrophage-specific scavenger receptor expressed in a subset of cMacs, has been linked to cardiovascular events through its serum soluble form. This study aimed to elucidate the functional role of the CD163+ cMacs subset in pressure overload-induced heart failure.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[10],"sample_count":10,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40343453"],"publication_contexts":[{"context_id":"disorder:Hypertensive_Heart_Disease","publication":"PMID:40343453"}],"publication":"PMID:40343453","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40343453","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Hypertensive Heart Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Hypertensive_Heart_Disease","name":"Hypertensive Heart Disease","kind":"Disorder","source_path":"kb/disorders/Hypertensive_Heart_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hypertensive_Heart_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertensive_Heart_Disease.html#dataset-geo-gse277624"}],"context_names":["Hypertensive Heart Disease"],"disease_names":["Hypertensive Heart Disease"],"disease_name":"Hypertensive Heart Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hypertensive_Heart_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hypertensive_Heart_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hypertensive_Heart_Disease.html#dataset-geo-gse277624"]},{"id":"dataset:geo:gse277674","accession":"geo:GSE277674","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE277674","title":"Digital Spatial Profiling of Human Kidney Biopsies from Patients with Minimal Change Disease","alternate_titles":[],"description":"Spatial transcriptomic profiling enables precise quantification of gene expression with simultaneous localization of expression profiles onto tissue structures. This new technology promises to improve our understanding of the disease mechanisms. Therefore, there is intense interest in applying these methods in clinical trials or as laboratory developed tests to aid in diagnosis of disease. Before these applications can been more broadly deployed in clinical research and diagnostics, it is necessary to thoroughly understand the technology’s performance in real world conditions.","alternate_descriptions":[],"data_types":["SPATIAL_TRANSCRIPTOMICS"],"data_type_labels":["Spatially resolved transcriptomics"],"data_type_label":"Spatially resolved transcriptomics","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[96],"sample_count":96,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40311874"],"publication_contexts":[{"context_id":"disorder:Minimal_Change_Disease","publication":"PMID:40311874"}],"publication":"PMID:40311874","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40311874","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Minimal Change Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Minimal_Change_Disease","name":"Minimal Change Disease","kind":"Disorder","source_path":"kb/disorders/Minimal_Change_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Minimal_Change_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Minimal_Change_Disease.html#dataset-geo-gse277674"}],"context_names":["Minimal Change Disease"],"disease_names":["Minimal Change Disease"],"disease_name":"Minimal Change Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Minimal_Change_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Minimal_Change_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Minimal_Change_Disease.html#dataset-geo-gse277674"]},{"id":"dataset:geo:gse277739","accession":"geo:GSE277739","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE277739","title":"Gene expression data of NMDAR-E Associated with Ovarian Teratoma","alternate_titles":[],"description":"Purpose: To identify significantly differentially expressed genes and to investigate the intricate molecular regulatory network underlying anti-NMDA receptor encephalitis associated with ovarian teratoma. Methods: This retrospective study analyzed ovarian teratoma samples from patients with and without NMDAR-E. We employed RNA sequencing for gene expression profiling. qPCR and Western blotting were used for gene and protein expression validation. Results: We identified 2524 significantly differentially expressed genes. The changes were notable in mRNA levels in ovarian teratomas associated with NMDAR-E.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[7],"sample_count":7,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41339905"],"publication_contexts":[{"context_id":"disorder:Anti-NMDA_Receptor_Encephalitis","publication":"PMID:41339905"}],"publication":"PMID:41339905","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41339905","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Anti-NMDA Receptor Encephalitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Anti-NMDA_Receptor_Encephalitis","name":"Anti-NMDA Receptor Encephalitis","kind":"Disorder","source_path":"kb/disorders/Anti-NMDA_Receptor_Encephalitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Anti-NMDA_Receptor_Encephalitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Anti-NMDA_Receptor_Encephalitis.html#dataset-geo-gse277739"}],"context_names":["Anti-NMDA Receptor Encephalitis"],"disease_names":["Anti-NMDA Receptor Encephalitis"],"disease_name":"Anti-NMDA Receptor Encephalitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Anti-NMDA_Receptor_Encephalitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Anti-NMDA_Receptor_Encephalitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Anti-NMDA_Receptor_Encephalitis.html#dataset-geo-gse277739"]},{"id":"dataset:geo:gse277780","accession":"geo:GSE277780","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE277780","title":"A common molecular mechanism underlying Cornelia de Lange and CHOPS syndromes","alternate_titles":[],"description":"The cohesin protein complex is essential for the formation of topologically associating domains (TADs) and chromatin loops on interphase chromosomes. For the loading onto chromosomes, cohesin requires the cohesin loader complex formed by NIPBL and MAU2. Cohesin localizes at enhancers and gene promoters with NIPBL in mammalian cells and forms enhancer-promoter loops. Cornelia de Lange syndrome (CdLS) is a rare, genetically heterogeneous disorder affecting multiple organs and systems during development, caused by mutations in the cohesin loader NIPBL gene (> 60% of patients), as well as in genes encoding cohesin, a chromatin regulator, BRD4, and cohesin-related factors.","alternate_descriptions":[],"data_types":["CHIP_SEQ"],"data_type_labels":["Chromatin immunoprecipitation sequencing"],"data_type_label":"Chromatin immunoprecipitation sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[16],"sample_count":16,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39983729"],"publication_contexts":[{"context_id":"disorder:Cornelia_de_Lange_Syndrome","publication":"PMID:39983729"}],"publication":"PMID:39983729","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39983729","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Cornelia de Lange syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Cornelia_de_Lange_Syndrome","name":"Cornelia de Lange syndrome","kind":"Disorder","source_path":"kb/disorders/Cornelia_de_Lange_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cornelia_de_Lange_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cornelia_de_Lange_syndrome.html#dataset-geo-gse277780"}],"context_names":["Cornelia de Lange syndrome"],"disease_names":["Cornelia de Lange syndrome"],"disease_name":"Cornelia de Lange syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cornelia_de_Lange_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cornelia_de_Lange_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cornelia_de_Lange_syndrome.html#dataset-geo-gse277780"]},{"id":"dataset:geo:gse277910","accession":"geo:GSE277910","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE277910","title":"10 Ehlers-Danlos SYndrome (EDS) patients","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[28],"sample_count":28,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40345454"],"publication_contexts":[{"context_id":"disorder:Ehlers-Danlos_Syndrome","publication":"PMID:40345454"}],"publication":"PMID:40345454","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40345454","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Ehlers-Danlos Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Ehlers-Danlos_Syndrome","name":"Ehlers-Danlos Syndrome","kind":"Disorder","source_path":"kb/disorders/Ehlers-Danlos_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ehlers-Danlos_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Ehlers-Danlos_Syndrome.html#dataset-geo-gse277910"}],"context_names":["Ehlers-Danlos Syndrome"],"disease_names":["Ehlers-Danlos Syndrome"],"disease_name":"Ehlers-Danlos Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Ehlers-Danlos_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ehlers-Danlos_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Ehlers-Danlos_Syndrome.html#dataset-geo-gse277910"]},{"id":"dataset:geo:gse278318","accession":"geo:GSE278318","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE278318","title":"Sex-biased ZRSR2 mutations in myeloid malignancies impair plasmacytoid dendritic cell activation and apoptosis [PDX]","alternate_titles":[],"description":"RNA-seq of BPDCN patient-derived xenografts from the study linking X-linked ZRSR2 loss to the disease's male predominance.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:34615655"],"publication_contexts":[{"context_id":"disorder:Blastic_Plasmacytoid_Dendritic_Cell_Neoplasm","publication":"PMID:34615655"}],"publication":"PMID:34615655","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34615655","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":[],"contexts":[{"id":"disorder:Blastic_Plasmacytoid_Dendritic_Cell_Neoplasm","name":"Blastic Plasmacytoid Dendritic Cell Neoplasm","kind":"Disorder","source_path":"kb/disorders/Blastic_Plasmacytoid_Dendritic_Cell_Neoplasm.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Blastic_Plasmacytoid_Dendritic_Cell_Neoplasm.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Blastic_Plasmacytoid_Dendritic_Cell_Neoplasm.html#dataset-geo-gse278318"}],"context_names":["Blastic Plasmacytoid Dendritic Cell Neoplasm"],"disease_names":["Blastic Plasmacytoid Dendritic Cell Neoplasm"],"disease_name":"Blastic Plasmacytoid Dendritic Cell Neoplasm","same_context_model_ids":["model:kb/disorders/Blastic_Plasmacytoid_Dendritic_Cell_Neoplasm.yaml:CAL-1 and GEN2.2 BPDCN cell lines","model:kb/disorders/Blastic_Plasmacytoid_Dendritic_Cell_Neoplasm.yaml:Tet2-edited HOXB8 dendritic differentiation culture"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Blastic_Plasmacytoid_Dendritic_Cell_Neoplasm.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Blastic_Plasmacytoid_Dendritic_Cell_Neoplasm.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Blastic_Plasmacytoid_Dendritic_Cell_Neoplasm.html#dataset-geo-gse278318"]},{"id":"dataset:geo:gse278421","accession":"geo:GSE278421","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE278421","title":"N-Palmitoylglycine activates transient receptor potential channel 5 and increases the risk of Brugada syndrome","alternate_titles":[],"description":"Brugada syndrome (BrS) is an arrhythmic disorder associated with an increased risk of sudden cardiac death; however, current treatment options are limited due to their side effects and variable efficacy. In this study, we employed Mendelian randomization analysis utilizing proteomic, transcriptomic, and metabolomic data to identify potential therapeutic targets for BrS. Our findings indicate that N-palmitoylglycine (PalGly) is linked to an increased risk of BrS and interacts with BrS-associated proteins, demonstrating moderate binding affinities for proteins such as DCC, CR1, CTSB, NAAA, DEFB1, EPHA1, IGF1/IGFBP3/ALS, and LTA.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10116","label":"Rattus norvegicus","display_label":"rat","url":"http://purl.obolibrary.org/obo/NCBITaxon_10116"}],"organism_labels":["Rattus norvegicus"],"organism_label":"Rattus norvegicus","sample_types":[],"sample_type_labels":[],"sample_counts":[10],"sample_count":10,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41315851"],"publication_contexts":[{"context_id":"disorder:Brugada_Syndrome","publication":"PMID:41315851"}],"publication":"PMID:41315851","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41315851","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Brugada syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Brugada_Syndrome","name":"Brugada syndrome","kind":"Disorder","source_path":"kb/disorders/Brugada_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Brugada_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Brugada_syndrome.html#dataset-geo-gse278421"}],"context_names":["Brugada syndrome"],"disease_names":["Brugada syndrome"],"disease_name":"Brugada syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Brugada_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Brugada_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Brugada_syndrome.html#dataset-geo-gse278421"]},{"id":"dataset:geo:gse278713","accession":"geo:GSE278713","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE278713","title":"Transcriptome-wide Profiling between Cystic and Solid Vestibular Schwannoma Patients Reveal Candidate Long noncoding RNA molecular signatures","alternate_titles":[],"description":"Vestibular Schwannoma (VS) is a benign tumor that arises from the Schwann cells of the VIII vestibulocochlear nerve. They contribute to 6-8% of the brain tumors and 80% of tumors originate from the cerebellopontine angle. Cystic vestibular schwannoma (cVS) represents 10% of vestibular schwannomas and are associated with an unpredictable growth behavior and poor surgical outcomes compared with solid vestibular schwannoma (sVS). Long non-coding RNAs (lncRNAs) belong to the class of non-coding RNAs and are known to regulate gene transcription and involved in chromatin remodeling via various mechanism.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42507076"],"publication_contexts":[{"context_id":"disorder:Schwannoma","publication":"PMID:42507076"}],"publication":"PMID:42507076","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42507076","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Schwannoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Schwannoma","name":"Schwannoma","kind":"Disorder","source_path":"kb/disorders/Schwannoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Schwannoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Schwannoma.html#dataset-geo-gse278713"}],"context_names":["Schwannoma"],"disease_names":["Schwannoma"],"disease_name":"Schwannoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Schwannoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Schwannoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Schwannoma.html#dataset-geo-gse278713"]},{"id":"dataset:geo:gse278723","accession":"geo:GSE278723","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE278723","title":"Differential Roles of Astrocytic CSF1 in Alzheimer's Disease and Cerebral Amyloid Angiopathy: Insights from Transcriptomic Analysis","alternate_titles":[],"description":"Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA) are neurodegenerative disorders characterized by the pathological deposition of amyloid-beta (Aβ) in the brain. Although both conditions share common pathogenic pathways, they exhibit distinct cellular manifestations and disease progression. Our study focused on the differential expression and role of astrocytic colony-stimulating factor 1 (CSF1) in these diseases. Using transcriptomic analysis of 248 brain tissue samples from the hippocampal-entorhinal system of 50 individuals, we identified a significant increase in CSF1 expression in the CA4 subfield of AD patients compared to a marked decrease in CAA.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[248],"sample_count":248,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39571157"],"publication_contexts":[{"context_id":"disorder:Cerebral_Amyloid_Angiopathy","publication":"PMID:39571157"}],"publication":"PMID:39571157","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39571157","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Cerebral Amyloid Angiopathy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Cerebral_Amyloid_Angiopathy","name":"Cerebral Amyloid Angiopathy","kind":"Disorder","source_path":"kb/disorders/Cerebral_Amyloid_Angiopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cerebral_Amyloid_Angiopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cerebral_Amyloid_Angiopathy.html#dataset-geo-gse278723"}],"context_names":["Cerebral Amyloid Angiopathy"],"disease_names":["Cerebral Amyloid Angiopathy"],"disease_name":"Cerebral Amyloid Angiopathy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cerebral_Amyloid_Angiopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cerebral_Amyloid_Angiopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cerebral_Amyloid_Angiopathy.html#dataset-geo-gse278723"]},{"id":"dataset:geo:gse278808","accession":"geo:GSE278808","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE278808","title":"Mutations of schizophrenia risk gene SETD1A dysregulate synaptic function in human neurons","alternate_titles":[],"description":"Schizophrenia (SCZ) is a complex neuropsychiatric disorder associated with both common risk variants of small effect sizes and rare risk variants of high penetrance. Rare protein truncating variants (PTVs) in SETD1A (SET Domain Containing 1A) show a strong association with SCZ; however, it remains largely unclear how rare PTVs in SETD1A contribute to the pathophysiology of SCZ. To understand the impact of SETD1A rare PTVs in human neurons, we CRISPR/Cas9-engineered five isogenic pairs of human induced pluripotent stem cells (iPSCs), with a recurrent heterozygous patient-specific PTV mutation c.4582-2delAG in two donor lines and a heterozygous frameshift mutation c.4596_4597insG (p.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[26],"sample_count":26,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40962831"],"publication_contexts":[{"context_id":"disorder:Schizophrenia","publication":"PMID:40962831"}],"publication":"PMID:40962831","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40962831","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Schizophrenia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Schizophrenia","name":"Schizophrenia","kind":"Disorder","source_path":"kb/disorders/Schizophrenia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Schizophrenia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Schizophrenia.html#dataset-geo-gse278808"}],"context_names":["Schizophrenia"],"disease_names":["Schizophrenia"],"disease_name":"Schizophrenia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Schizophrenia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Schizophrenia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Schizophrenia.html#dataset-geo-gse278808"]},{"id":"dataset:geo:gse278882","accession":"geo:GSE278882","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE278882","title":"Esoinophilic fasciitis and morphea share gene signatures of inflammatory cell death, self-DNA recognition, and JAK/STAT signaling","alternate_titles":[],"description":"The pathogenesis of eosinophilic fasciitis (EF) and morphea is poorly understood. We analyzed skin biopsies from EF and morphea patients compared to adult healthy skin (HS) using gene expression profiling, Ingenuity Pathway Analysis, and immunostaining. EF gene expression showed significant overlap with morphea. 51/61 differentially expressed genes (DEG), 80/99 canonical pathways, and 40/51 upstream regulators were shared in EF and morphea. Both conditions exhibited robust T cell activation and cytotoxic signatures despite their pauci-inflammatory histological appearance, suggesting small numbers of T cells may drive injury, inflammation, and fibrosis.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[24],"sample_count":24,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Eosinophilic Fasciitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Eosinophilic_Fasciitis","name":"Eosinophilic Fasciitis","kind":"Disorder","source_path":"kb/disorders/Eosinophilic_Fasciitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Eosinophilic_Fasciitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Eosinophilic_Fasciitis.html#dataset-geo-gse278882"}],"context_names":["Eosinophilic Fasciitis"],"disease_names":["Eosinophilic Fasciitis"],"disease_name":"Eosinophilic Fasciitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Eosinophilic_Fasciitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Eosinophilic_Fasciitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Eosinophilic_Fasciitis.html#dataset-geo-gse278882"]},{"id":"dataset:geo:gse278888","accession":"geo:GSE278888","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE278888","title":"Differing Epithelial and Immunologic Activation Patterns Following Food Reintroduction Reveal Differential Transcriptional Profiles in Active Eosinophilic Esophagitis","alternate_titles":[],"description":"During food trigger reintroductions, eosinophilia can recur in a patchy manner both endoscopically and histologically. We postulated that areas containing low eosinophils represented the early stage of EoE recurrence, while areas with >15 eos/HPF represented established active EoE. We identified ten patients with prior pan-esophageal EoE who experienced patchy eosinophilia during trigger food reintroduction. The progression of recurrent EoE is illustrated by the transcriptional changes occurring from baseline remission through recurrent low and high eosinophil tissues in those with paired time points.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[28],"sample_count":28,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39490770"],"publication_contexts":[{"context_id":"disorder:Eosinophilic_Esophagitis","publication":"PMID:39490770"}],"publication":"PMID:39490770","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39490770","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Eosinophilic Esophagitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Eosinophilic_Esophagitis","name":"Eosinophilic Esophagitis","kind":"Disorder","source_path":"kb/disorders/Eosinophilic_Esophagitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Eosinophilic_Esophagitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Eosinophilic_Esophagitis.html#dataset-geo-gse278888"}],"context_names":["Eosinophilic Esophagitis"],"disease_names":["Eosinophilic Esophagitis"],"disease_name":"Eosinophilic Esophagitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Eosinophilic_Esophagitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Eosinophilic_Esophagitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Eosinophilic_Esophagitis.html#dataset-geo-gse278888"]},{"id":"dataset:geo:gse279030","accession":"geo:GSE279030","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE279030","title":"The effect of methylation on the let-7-BCL2L1-BCL2 axis and the potential use of hypomethylating and BH3 mimetic drugs in histiocytic neoplasms","alternate_titles":[],"description":"The histiocytoses [Erdheim-Chester Disease (ECD), Langerhans cell histiocytosis (LCH), and Rosai-Dorfman-Destombes disease (RDD)] are characterized by the infiltration of monocytes, macrophages, and dendritic cells in normal tissues, leading to significant morbidity due to disruption of critical organ systems. While their pathogenesis involves MAPK-ERK pathway mutations, their epigenetic landscape remains poorly understood. Epigenetic mechanisms such as DNA methylation, histone modification, and non-coding RNA are crucial in gene expression regulation and cancer development. We previously identified a distinct non-coding RNA profile in histiocytosis patients compared to controls.","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[34],"sample_count":34,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39516372"],"publication_contexts":[{"context_id":"disorder:Erdheim-Chester_Disease","publication":"PMID:39516372"}],"publication":"PMID:39516372","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39516372","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Erdheim-Chester Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Erdheim-Chester_Disease","name":"Erdheim-Chester Disease","kind":"Disorder","source_path":"kb/disorders/Erdheim-Chester_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Erdheim-Chester_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Erdheim-Chester_Disease.html#dataset-geo-gse279030"}],"context_names":["Erdheim-Chester Disease"],"disease_names":["Erdheim-Chester Disease"],"disease_name":"Erdheim-Chester Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Erdheim-Chester_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Erdheim-Chester_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Erdheim-Chester_Disease.html#dataset-geo-gse279030"]},{"id":"dataset:geo:gse279246","accession":"geo:GSE279246","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE279246","title":"TAK1 operates at the primary cilium in non-canonical TGFB/BMP signaling to control heart development","alternate_titles":[],"description":"Bulk transcriptomic and mechanistic developmental dataset linking TAK1/MAP3K7 dysfunction to syndromic congenital heart disease, cardiomyocyte differentiation failure, and altered cardiac developmental gene expression.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:7955","label":"Danio rerio","display_label":"zebrafish","url":"http://purl.obolibrary.org/obo/NCBITaxon_7955"}],"organism_labels":["Danio rerio"],"organism_label":"Danio rerio","sample_types":[{"id":"UBERON:0000948","label":"heart","display_label":"heart","url":"http://purl.obolibrary.org/obo/UBERON_0000948"}],"sample_type_labels":["heart"],"sample_counts":[],"sample_count":null,"conditions":["cardiospondylocarpofacial syndrome","congenital heart disease","MAP3K7/TAK1 dysfunction"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[{"statement":"TAK1 loss downregulates core cardiac transcriptional programs, sarcomeric genes, and extracellular matrix genes in mutant hearts.","evidence":[{"reference":"GEO:GSE279246","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE279246","reference_title":"TAK1 operates at the primary cilium in non-canonical TGFB/BMP signaling to control heart development","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"RNA sequencing of tak1-/- mutant hearts showed downregulation of genes encoding core cardiac transcription factors, sarcomeric proteins and extracellular matrix proteins.","explanation":"This directly supports the dataset's relevance to CSCFS cardiac developmental mechanisms."}]},{"statement":"TAK1 perturbation inhibits ciliary signaling and cardiomyocyte differentiation in vitro.","evidence":[{"reference":"GEO:GSE279246","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE279246","reference_title":"TAK1 operates at the primary cilium in non-canonical TGFB/BMP signaling to control heart development","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Consistent with these findings, CRISPR/Cas9-mediated editing of TAK1 or administration of small molecule inhibitors targeting TAK1 inhibited ciliary signaling and cardiomyocyte differentiation in vitro","explanation":"This complements the zebrafish transcriptomic finding with cell-based evidence of impaired cardiomyogenesis."}]}],"findings_text":["TAK1 loss downregulates core cardiac transcriptional programs, sarcomeric genes, and extracellular matrix genes in mutant hearts.","TAK1 perturbation inhibits ciliary signaling and cardiomyocyte differentiation in vitro."],"evidence":[{"reference":"GEO:GSE279246","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE279246","reference_title":"TAK1 operates at the primary cilium in non-canonical TGFB/BMP signaling to control heart development","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"RNA sequencing of tak1-/- mutant hearts showed downregulation of genes encoding core cardiac transcription factors, sarcomeric proteins and extracellular matrix proteins.","explanation":"This supports GEO:GSE279246 as a disease-relevant zebrafish cardiac transcriptomic dataset for TAK1 biology."},{"reference":"GEO:GSE279246","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE279246","reference_title":"TAK1 operates at the primary cilium in non-canonical TGFB/BMP signaling to control heart development","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Consistent with these findings, CRISPR/Cas9-mediated editing of TAK1 or administration of small molecule inhibitors targeting TAK1 inhibited ciliary signaling and cardiomyocyte differentiation in vitro","explanation":"This complements the zebrafish transcriptomic finding with cell-based evidence of impaired cardiomyogenesis."}],"notes":[],"contexts":[{"id":"disorder:Cardiospondylocarpofacial_Syndrome","name":"Cardiospondylocarpofacial syndrome","kind":"Disorder","source_path":"kb/disorders/Cardiospondylocarpofacial_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cardiospondylocarpofacial_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cardiospondylocarpofacial_syndrome.html#dataset-geo-gse279246"}],"context_names":["Cardiospondylocarpofacial syndrome"],"disease_names":["Cardiospondylocarpofacial syndrome"],"disease_name":"Cardiospondylocarpofacial syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cardiospondylocarpofacial_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cardiospondylocarpofacial_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cardiospondylocarpofacial_syndrome.html#dataset-geo-gse279246"]},{"id":"dataset:geo:gse279632","accession":"geo:GSE279632","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE279632","title":"Single-cell transcriptome analysis reveals CD34 as a marker of human sinoatrial node pacemaker cardiomyocytes [CITE-seq]","alternate_titles":[],"description":"The two-sample CITE-seq component of a study that resolved the human sinoatrial node into Core Pacemaker, Sinus Venosus and Transitional pacemaker subtypes and identified CD34 as a surface marker enriching functional pacemaker cells. This accession holds only that component; the single-nuclei and single-cell RNA sequencing of fetal and stem cell-derived sinoatrial node cells that the quoted sentence describes sits in sibling accessions of the same series. This is a reference dataset for the cell type whose failure defines SSS2, not an SSS2 patient cohort, and it contains no HCN4 variant carriers. Its value here is that it makes the affected compartment addressable: a CD34 sort yields the pacemaker cells in which an HCN4 allele would have to be assayed.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39604360"],"publication_contexts":[{"context_id":"disorder:Sick_Sinus_Syndrome_2_Autosomal_Dominant","publication":"PMID:39604360"}],"publication":"PMID:39604360","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39604360","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:39604360","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39604360","reference_title":"Single-cell transcriptome analysis reveals CD34 as a marker of human sinoatrial node pacemaker cardiomyocytes.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Here we use single-nuclei/cell RNA sequencing of fetal and human pluripotent stem cell-derived sinoatrial node cells to reveal that they consist of three subtypes of pacemaker cells: Core Pacemaker, Sinus Venosus, and Transitional Cells.","explanation":"Describes the study this accession belongs to and the material it profiles, human sinoatrial node pacemaker cells at single-cell resolution. The sentence covers the whole series rather than this CITE-seq component alone, which the description states."}],"notes":["Relevance is at the level of cell type rather than genotype. Verified with just verify-datasets."],"contexts":[{"id":"disorder:Sick_Sinus_Syndrome_2_Autosomal_Dominant","name":"Sick Sinus Syndrome 2, Autosomal Dominant","kind":"Disorder","source_path":"kb/disorders/Sick_Sinus_Syndrome_2_Autosomal_Dominant.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sick_Sinus_Syndrome_2_Autosomal_Dominant.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Sick_Sinus_Syndrome_2,_Autosomal_Dominant.html#dataset-geo-gse279632"}],"context_names":["Sick Sinus Syndrome 2, Autosomal Dominant"],"disease_names":["Sick Sinus Syndrome 2, Autosomal Dominant"],"disease_name":"Sick Sinus Syndrome 2, Autosomal Dominant","same_context_model_ids":["model:kb/disorders/Sick_Sinus_Syndrome_2_Autosomal_Dominant.yaml:hiPSC-derived pacemaker cardiomyocytes as a human I_f measurement platform","model:kb/disorders/Sick_Sinus_Syndrome_2_Autosomal_Dominant.yaml:Patient-derived hiPSC lines carrying a heterozygous and a homozygous HCN4 variant (UKMi009-A, UKMi011-A)"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Sick_Sinus_Syndrome_2_Autosomal_Dominant.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sick_Sinus_Syndrome_2_Autosomal_Dominant.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Sick_Sinus_Syndrome_2,_Autosomal_Dominant.html#dataset-geo-gse279632"]},{"id":"dataset:geo:gse280021","accession":"geo:GSE280021","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE280021","title":"Dynamics of Th1/Th17 Responses and Antimicrobial Pathways in Leprosy Skin Lesions","alternate_titles":[],"description":"Reversal reactions (RR) in leprosy provide a unique opportunity to study the dynamics of the immune response against intracellular bacteria in humans. These episodes are often severe and difficult to treat, frequently progressing to permanent disabilities. We performed RNA sequencing on paired skin biopsy specimens from nine leprosy patients before and during RR, identifying a 64-gene antimicrobial response signature that correlated with the concomitant decrease in Mycobacterium leprae bacilli in RR patients. The upstream regulators of this signature included both innate (IL-1β, TNF) and adaptive (IFN-γ, IL-17) cytokines, indicating induction of both Th1 and Th17 responses.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[45],"sample_count":45,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40569678"],"publication_contexts":[{"context_id":"disorder:Leprosy","publication":"PMID:40569678"}],"publication":"PMID:40569678","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40569678","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Leprosy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Leprosy","name":"Leprosy","kind":"Disorder","source_path":"kb/disorders/Leprosy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Leprosy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Leprosy.html#dataset-geo-gse280021"}],"context_names":["Leprosy"],"disease_names":["Leprosy"],"disease_name":"Leprosy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Leprosy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Leprosy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Leprosy.html#dataset-geo-gse280021"]},{"id":"dataset:geo:gse281080","accession":"geo:GSE281080","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE281080","title":"Transcriptomic profiling of prolonged-culture iPSC-derived kidney organoids and X-linked Alport syndrome organoid models carrying COL4A5 deep-intronic variants","alternate_titles":[],"description":"Kidney organoids serve as an invaluable platform for modeling hereditary renal diseases and developing therapeutic interventions. While various kidney organoid differentiation protocols have been developed, the protocol introduced by Morizane et al. was among the first to generate kidney organoids from induced pluripotent stem cells (iPSCs). By using a modified version of this protocol, we successfully generated kidney organoids in 21 days. Most studies on kidney organoids focus on early stages, typically between days 21 and 29, leaving the gene expression dynamics during prolonged culture less explored.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[24],"sample_count":24,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Alport Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Alport_Syndrome","name":"Alport Syndrome","kind":"Disorder","source_path":"kb/disorders/Alport_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alport_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Alport_Syndrome.html#dataset-geo-gse281080"}],"context_names":["Alport Syndrome"],"disease_names":["Alport Syndrome"],"disease_name":"Alport Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Alport_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alport_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Alport_Syndrome.html#dataset-geo-gse281080"]},{"id":"dataset:geo:gse281147","accession":"geo:GSE281147","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE281147","title":"MicroRNA-371-373 cluster and methylome analysis suggests that a subset of “somatic-type” malignancies arising in germ cell tumors may originate in yolk sac tumor components","alternate_titles":[],"description":"Background: Somatic-type malignancies (SM) arising in germ cell tumors (GCTs) represent aggressive and chemoresistant neoplasms frequently occurring as metastases after chemotherapy. Historically, SM have been interpreted as originating in teratoma; however, recent observations suggest that a subset may derive from yolk sac tumor. In this study, we evaluate the relationship between conventional histologic types of GCT and SM of germ cell origin by assessing expression of miR-371~373 and genomic methylation.","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[51],"sample_count":51,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40152072"],"publication_contexts":[{"context_id":"disorder:Yolk_Sac_Tumor","publication":"PMID:40152072"}],"publication":"PMID:40152072","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40152072","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Yolk Sac Tumor (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Yolk_Sac_Tumor","name":"Yolk Sac Tumor","kind":"Disorder","source_path":"kb/disorders/Yolk_Sac_Tumor.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Yolk_Sac_Tumor.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Yolk_Sac_Tumor.html#dataset-geo-gse281147"}],"context_names":["Yolk Sac Tumor"],"disease_names":["Yolk Sac Tumor"],"disease_name":"Yolk Sac Tumor","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Yolk_Sac_Tumor.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Yolk_Sac_Tumor.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Yolk_Sac_Tumor.html#dataset-geo-gse281147"]},{"id":"dataset:geo:gse281263","accession":"geo:GSE281263","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE281263","title":"Identification of a novel PDC-E2 epitope in Primary Biliary Cholangitis and application for engineered Treg therapy","alternate_titles":[],"description":"Background and Aims: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease, characterized by progressive destruction of small intrahepatic bile ducts and portal inflammation. Treatment options are limited with reliance on liver transplantation in advanced cases. The adaptive immune response is implicated in disease pathogenesis by both the presence of anti-mitochondrial antibodies targeting the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2), in 90-95% of patients, and T cells infiltrating the portal tracts in affected individuals.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[632],"sample_count":632,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39476446"],"publication_contexts":[{"context_id":"disorder:Primary_Biliary_Cholangitis","publication":"PMID:39476446"}],"publication":"PMID:39476446","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39476446","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Primary Biliary Cholangitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Primary_Biliary_Cholangitis","name":"Primary Biliary Cholangitis","kind":"Disorder","source_path":"kb/disorders/Primary_Biliary_Cholangitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Primary_Biliary_Cholangitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Biliary_Cholangitis.html#dataset-geo-gse281263"}],"context_names":["Primary Biliary Cholangitis"],"disease_names":["Primary Biliary Cholangitis"],"disease_name":"Primary Biliary Cholangitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Primary_Biliary_Cholangitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Primary_Biliary_Cholangitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Primary_Biliary_Cholangitis.html#dataset-geo-gse281263"]},{"id":"dataset:geo:gse281593","accession":"geo:GSE281593","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE281593","title":"Systems Biology-Based Assessment of Immune Responses to Whole Cell and Acellular Pertussis Vaccines: Rationale, Methodology and Enrollment Procedures for Omics Workflows","alternate_titles":[],"description":"PBMC RNA-seq comparing transcriptional responses in infants receiving DTP (whole-cell pertussis with diphtheria and tetanus toxoids) versus DTaP primary vaccination.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0000178","label":"blood","display_label":"blood","url":"http://purl.obolibrary.org/obo/UBERON_0000178"}],"sample_type_labels":["blood"],"sample_counts":[],"sample_count":null,"conditions":["DTP primary vaccination","DTaP primary vaccination"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40789865"],"publication_contexts":[{"context_id":"disorder:Tetanus","publication":"PMID:40789865"}],"publication":"PMID:40789865","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40789865","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:40789865","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40789865","reference_title":"Systems biology-based assessment of immune responses to whole cell and acellular pertussis vaccines.","supports":"SUPPORT","evidence_source":null,"snippet":"Given the local and systemic adverse reactions associated with whole-cell pertussis vaccines combined with diphtheria and tetanus toxoids (DTP), acellular pertussis vaccines combined with the same toxoids (DTaP) were developed in the 1990s.","explanation":"Confirms the study compares DTP and DTaP vaccinations that include tetanus toxoid, using gene expression profiling."}],"notes":["RNA-seq and ribosome profiling study of infant PBMCs after primary DTP vs DTaP vaccination, capturing tetanus toxoid-containing responses."],"contexts":[{"id":"disorder:Tetanus","name":"Tetanus","kind":"Disorder","source_path":"kb/disorders/Tetanus.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Tetanus.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Tetanus.html#dataset-geo-gse281593"}],"context_names":["Tetanus"],"disease_names":["Tetanus"],"disease_name":"Tetanus","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Tetanus.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Tetanus.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Tetanus.html#dataset-geo-gse281593"]},{"id":"dataset:geo:gse281597","accession":"geo:GSE281597","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE281597","title":"The transcriptional profile of extracellular vesicles extracted from cerebrospinal flood in patients with multiple system atrophy, Parkinson's disease, amyotrophic lateral sclerosis","alternate_titles":[],"description":"Extracellular vesicles (EVs) play a role in intercellular communication by transferring proteins and/or transcripts. The profile of proteins and/or transcripts in EVs may differentiate multiple system atrophy (MSA) from Parkinson's disease. In the present study, we performed transcriptome analysis of EVs extracted from cerebrospinal flood of patients with multiple system atrophy, Parkinson's disease, amyotrophic lateral sclerosis.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[40],"sample_count":40,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41166771"],"publication_contexts":[{"context_id":"disorder:Multiple_System_Atrophy","publication":"PMID:41166771"}],"publication":"PMID:41166771","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41166771","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Multiple System Atrophy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Multiple_System_Atrophy","name":"Multiple System Atrophy","kind":"Disorder","source_path":"kb/disorders/Multiple_System_Atrophy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Multiple_System_Atrophy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Multiple_System_Atrophy.html#dataset-geo-gse281597"}],"context_names":["Multiple System Atrophy"],"disease_names":["Multiple System Atrophy"],"disease_name":"Multiple System Atrophy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Multiple_System_Atrophy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Multiple_System_Atrophy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Multiple_System_Atrophy.html#dataset-geo-gse281597"]},{"id":"dataset:geo:gse281622","accession":"geo:GSE281622","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE281622","title":"Cortical versus hippocampal network dysfunction in a human brain assembloid model of epilepsy and intellectual disability","alternate_titles":[],"description":"Neurodevelopmental disorders often impair multiple cognitive domains. For instance, a genetic epilepsy syndrome might cause seizures due to cortical hyperexcitability and present with memory impairments arising from hippocampal dysfunction. This study examines how a single disorder differentially affects distinct brain regions by using human patient iPSC-derived cortical- and hippocampal-ganglionic eminence assembloids to model Developmental and Epileptic Encephalopathy 13 (DEE-13), a condition arising from gain-of-function mutations in the SCN8A gene.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40925365"],"publication_contexts":[{"context_id":"disorder:Genetic_Developmental_and_Epileptic_Encephalopathy","publication":"PMID:40925365"}],"publication":"PMID:40925365","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40925365","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Genetic Developmental and Epileptic Encephalopathy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Genetic_Developmental_and_Epileptic_Encephalopathy","name":"Genetic Developmental and Epileptic Encephalopathy","kind":"Disorder","source_path":"kb/disorders/Genetic_Developmental_and_Epileptic_Encephalopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Genetic_Developmental_and_Epileptic_Encephalopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Genetic_Developmental_and_Epileptic_Encephalopathy.html#dataset-geo-gse281622"}],"context_names":["Genetic Developmental and Epileptic Encephalopathy"],"disease_names":["Genetic Developmental and Epileptic Encephalopathy"],"disease_name":"Genetic Developmental and Epileptic Encephalopathy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Genetic_Developmental_and_Epileptic_Encephalopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Genetic_Developmental_and_Epileptic_Encephalopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Genetic_Developmental_and_Epileptic_Encephalopathy.html#dataset-geo-gse281622"]},{"id":"dataset:geo:gse281635","accession":"geo:GSE281635","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE281635","title":"Molecular Profiling of the Appendix in Pediatric Inflammatory Bowel Diseases","alternate_titles":[],"description":"Clinical studies suggest a critical role for the appendix in the pathogenesis of inflammatory bowel diseases (IBD), including Crohn disease (CD) and ulcerative colitis (UC), as indicated by the presence of peri-appendicular patches in UC and the beneficial effects of appendectomy in UC. However, the underlying mechanisms remain unclear. To address this gap, we characterized microbial species, associated patterns, and host-microbiota interactions in the appendix and non-inflamed regions of the colon tissue and mucus from pediatric IBD and non-IBD patients (n=15).","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[15],"sample_count":15,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Crohn Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Crohn_Disease","name":"Crohn Disease","kind":"Disorder","source_path":"kb/disorders/Crohn_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Crohn_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Crohn_Disease.html#dataset-geo-gse281635"}],"context_names":["Crohn Disease"],"disease_names":["Crohn Disease"],"disease_name":"Crohn Disease","same_context_model_ids":["model:kb/disorders/Crohn_Disease.yaml:Enteroendocrine-deficient intestinal enteroid barrier model","model:kb/disorders/Crohn_Disease.yaml:Primary human small-intestinal monolayer barrier model","model:kb/disorders/Crohn_Disease.yaml:PSC-derived intestinal organoid-macrophage coculture model"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Crohn_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Crohn_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Crohn_Disease.html#dataset-geo-gse281635"]},{"id":"dataset:geo:gse281658","accession":"geo:GSE281658","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE281658","title":"IGF2 deficiency induces sarcopenia and muscle functional decline","alternate_titles":[],"description":"Single-cell RNA-seq of an IGF2-deficiency model producing sarcopenia and functional decline, bearing on pathophysiology#Declining Anabolic Hormone Signalling.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Mouse data, no linked publication in the GEO record. Selected by manual relevance triage and accession-verified. No evidence block, as above."],"contexts":[{"id":"disorder:Sarcopenia","name":"Sarcopenia","kind":"Disorder","source_path":"kb/disorders/Sarcopenia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sarcopenia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Sarcopenia.html#dataset-geo-gse281658"}],"context_names":["Sarcopenia"],"disease_names":["Sarcopenia"],"disease_name":"Sarcopenia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Sarcopenia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sarcopenia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Sarcopenia.html#dataset-geo-gse281658"]},{"id":"dataset:geo:gse281938","accession":"geo:GSE281938","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE281938","title":"Porphyromonas gingivalis inhibits Respiratory Syncytial Virus infection while suppressing anti-viral immunity","alternate_titles":[],"description":"Colonizing microbiota can differentially impact the outcomes of viral infections. While synergistic interactions between invading viruses and specific bacterial colonizers can enhance viral infectivity, resulting in severe disease, other bacteria can play a more antagonistic role by destabilizing viral particles, thus protecting against infection. Here, we explored whether Porphyromonas gingivalis (Pg), a periodontal bacterial pathogen that can translocate to the airways, increases susceptibility to infection with the respiratory syncytial virus (RSV) and Sendai virus (SeV).","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[20],"sample_count":20,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42060722"],"publication_contexts":[{"context_id":"disorder:Respiratory_Syncytial_Virus_Infection","publication":"PMID:42060722"}],"publication":"PMID:42060722","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42060722","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Respiratory Syncytial Virus Infection (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Respiratory_Syncytial_Virus_Infection","name":"Respiratory Syncytial Virus Infection","kind":"Disorder","source_path":"kb/disorders/Respiratory_Syncytial_Virus_Infection.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Respiratory_Syncytial_Virus_Infection.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Respiratory_Syncytial_Virus_Infection.html#dataset-geo-gse281938"}],"context_names":["Respiratory Syncytial Virus Infection"],"disease_names":["Respiratory Syncytial Virus Infection"],"disease_name":"Respiratory Syncytial Virus Infection","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Respiratory_Syncytial_Virus_Infection.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Respiratory_Syncytial_Virus_Infection.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Respiratory_Syncytial_Virus_Infection.html#dataset-geo-gse281938"]},{"id":"dataset:geo:gse281962","accession":"geo:GSE281962","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE281962","title":"Temporal Dynamics of Gene and Protein Expression Follow Volumetric Muscle Loss","alternate_titles":[],"description":"Here, we performed time-series analysis of transcriptomic and proteomic changes associated with VML in a mouse model, focusing on the dynamics of gene and protein expression patterns at up to three weeks after muscle injury. We identified signaling pathways associated with temporal expression patterns that fail to restore within 3 weeks after VML, including those with sustained upregulation or downregulation. Using temporal expression analysis, we identified Sp1 as a novel molecular mediator of dysregulated muscle recovery after VML as well as elucidated pro-inflammatory and extracellular matrix (ECM) remodeling pathways mediating the remodeling process.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[27],"sample_count":27,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40677917"],"publication_contexts":[{"context_id":"disorder:Volumetric_Muscle_Loss","publication":"PMID:40677917"}],"publication":"PMID:40677917","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40677917","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Volumetric Muscle Loss (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Volumetric_Muscle_Loss","name":"Volumetric Muscle Loss","kind":"Disorder","source_path":"kb/disorders/Volumetric_Muscle_Loss.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Volumetric_Muscle_Loss.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Volumetric_Muscle_Loss.html#dataset-geo-gse281962"}],"context_names":["Volumetric Muscle Loss"],"disease_names":["Volumetric Muscle Loss"],"disease_name":"Volumetric Muscle Loss","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Volumetric_Muscle_Loss.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Volumetric_Muscle_Loss.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Volumetric_Muscle_Loss.html#dataset-geo-gse281962"]},{"id":"dataset:geo:gse282042","accession":"geo:GSE282042","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE282042","title":"RNA-seq analysis of human monocytes in patients with and without coronary atherosclerosis","alternate_titles":[],"description":"We conducted RNA-Seq transcriptome profiling on monocytes isolated from patients undergoing coronary angiography. After the procedure, patients were divided into two groups: those without coronary artery stenosis (\"w.o. CA\", n=11) and those with coronary artery stenosis (\"w. CA\", n=9). All patients were men, aged 61±6 years. CD14+ monocytes were isolated, and RNA-seq was performed on the Illumina NextSeq 2000 platform. This data was analyzed to identify changes in gene expression profiles associated with coronary atherosclerosis. Transcriptome analysis revealed an upregulation of numerous inflammatory genes.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[20],"sample_count":20,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40350260"],"publication_contexts":[{"context_id":"disorder:Coronary_Artery_Disease","publication":"PMID:40350260"}],"publication":"PMID:40350260","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40350260","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Coronary Artery Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Coronary_Artery_Disease","name":"Coronary Artery Disease","kind":"Disorder","source_path":"kb/disorders/Coronary_Artery_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Coronary_Artery_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Coronary_Artery_Disease.html#dataset-geo-gse282042"}],"context_names":["Coronary Artery Disease"],"disease_names":["Coronary Artery Disease"],"disease_name":"Coronary Artery Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Coronary_Artery_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Coronary_Artery_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Coronary_Artery_Disease.html#dataset-geo-gse282042"]},{"id":"dataset:geo:gse282079","accession":"geo:GSE282079","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE282079","title":"NETSseq Reveals Inflammatory and Aging Mechanisms in Distinct Cell Types Driving Cerebellar Decline in Ataxia Telangiectasia","alternate_titles":[],"description":"The cellular and molecular changes driving the neurological abnormalities associated with the loss or functional deficiency of the ataxia–telangiectasia mutated (ATM) protein are not well understood. In this study, we applied our proprietary Nuclear Enriched Transcript Sort sequencing (NETSseq) platform to investigate changes in cell type composition and gene expression patterns in human cerebellar post-mortem tissue from ataxia–telangiectasia (A-T) donors and non-neurodegenerative disease control donors. Compared to single-cell technologies, NETSseq provided a more robust detection of lowly expressed and differentially expressed genes.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[318],"sample_count":318,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40959764"],"publication_contexts":[{"context_id":"disorder:Ataxia_Telangiectasia","publication":"PMID:40959764"}],"publication":"PMID:40959764","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40959764","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Ataxia-telangiectasia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Ataxia_Telangiectasia","name":"Ataxia-telangiectasia","kind":"Disorder","source_path":"kb/disorders/Ataxia_Telangiectasia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ataxia_Telangiectasia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Ataxia-telangiectasia.html#dataset-geo-gse282079"}],"context_names":["Ataxia-telangiectasia"],"disease_names":["Ataxia-telangiectasia"],"disease_name":"Ataxia-telangiectasia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Ataxia_Telangiectasia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ataxia_Telangiectasia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Ataxia-telangiectasia.html#dataset-geo-gse282079"]},{"id":"dataset:geo:gse28217","accession":"geo:GSE28217","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE28217","title":"NID2 and HOXA9 promoter hypermethylation as biomarkers to prevent and detect Oral Cavity Squamous Cell Carcinoma","alternate_titles":[],"description":"Differentially methylated oral squamous cell carcinoma (OSCC) biomarkers, identified in-vitro and validated in well-characterized surgical specimens, have shown poor clinical correlation in cohorts with different risk profiles. To overcome this lack of relevance we used the HumanMethylation27 BeadChip, publicly available methylation and expression array data, and Quantitative Methylation Specific PCR to uncover differential methylation in OSCC clinical samples with heterogeneous risk profiles.","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:21558411"],"publication_contexts":[{"context_id":"disorder:Oral_Cavity_Squamous_Cell_Carcinoma","publication":"PMID:21558411"}],"publication":"PMID:21558411","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/21558411","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Oral Cavity Squamous Cell Carcinoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Oral_Cavity_Squamous_Cell_Carcinoma","name":"Oral Cavity Squamous Cell Carcinoma","kind":"Disorder","source_path":"kb/disorders/Oral_Cavity_Squamous_Cell_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Oral_Cavity_Squamous_Cell_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Oral_Cavity_Squamous_Cell_Carcinoma.html#dataset-geo-gse28217"}],"context_names":["Oral Cavity Squamous Cell Carcinoma"],"disease_names":["Oral Cavity Squamous Cell Carcinoma"],"disease_name":"Oral Cavity Squamous Cell Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Oral_Cavity_Squamous_Cell_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Oral_Cavity_Squamous_Cell_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Oral_Cavity_Squamous_Cell_Carcinoma.html#dataset-geo-gse28217"]},{"id":"dataset:geo:gse282216","accession":"geo:GSE282216","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE282216","title":"Plasma DNA Methylation-Based Biomarkers for MPNST Detection in Patients With Neurofibromatosis Type 1","alternate_titles":[],"description":"Malignant peripheral nerve sheath tumor (MPNST) development is characterized by an altered DNA methylation landscape, which presents a promising area for developing MPNST‐specific biomarkers for screening patients with NF1. Genome‐wide DNA methylation profiling of a cohort of 13 patients with MPNST (29 samples of tumor and adjacent neurofibroma tissues) and of NF1‐MPNST cell lines was performed to identify and validate candidate MPNST‐specific CpG sites (CpGs). A logistic regression prediction model was constructed to select MPNST‐specific CpGs distinct from adjacent neurofibromas and normal tissues.","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[43],"sample_count":43,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39600120"],"publication_contexts":[{"context_id":"disorder:Neurofibroma","publication":"PMID:39600120"}],"publication":"PMID:39600120","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39600120","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Neurofibroma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Neurofibroma","name":"Neurofibroma","kind":"Disorder","source_path":"kb/disorders/Neurofibroma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Neurofibroma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Neurofibroma.html#dataset-geo-gse282216"}],"context_names":["Neurofibroma"],"disease_names":["Neurofibroma"],"disease_name":"Neurofibroma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Neurofibroma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Neurofibroma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Neurofibroma.html#dataset-geo-gse282216"]},{"id":"dataset:geo:gse282236","accession":"geo:GSE282236","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE282236","title":"Plasma-Derived Exosomes in Chronic Spontaneous Urticaria Induce the Release of Inflammatory Mediators from Mast cell through miRNA-619-5p/SOCS4 Pathway","alternate_titles":[],"description":"This study aims to explore the critical role of exosomes derived from plasma of patients in the progression of CSU.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[26],"sample_count":26,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Urticaria (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Urticaria","name":"Urticaria","kind":"Disorder","source_path":"kb/disorders/Urticaria.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Urticaria.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Urticaria.html#dataset-geo-gse282236"}],"context_names":["Urticaria"],"disease_names":["Urticaria"],"disease_name":"Urticaria","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Urticaria.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Urticaria.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Urticaria.html#dataset-geo-gse282236"]},{"id":"dataset:geo:gse282430","accession":"geo:GSE282430","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE282430","title":"Gene expression analysis of human parotid salivary glands in cases of Mucoepidermoid Carcinoma via bulk RNA sequencing","alternate_titles":[],"description":"Mucoepidermoid carcinoma (MEC) is the most frequently occurring salivary gland malignancy. Here, we investigated transcriptomic profiles of human adult salivary glands and MEC tumors to assess programs involved in MEC progression. MEC tumors were stratified by disease grade and CRTC1/MAML2 fusion status. The bioinformatics of our study will provide critical steps in elucidating salivary MEC progression and suggest a new candidates for targeted therapies in the treatment of high-grade MEC.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[28],"sample_count":28,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40542202"],"publication_contexts":[{"context_id":"disorder:Mucoepidermoid_Carcinoma","publication":"PMID:40542202"}],"publication":"PMID:40542202","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40542202","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Mucoepidermoid Carcinoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Mucoepidermoid_Carcinoma","name":"Mucoepidermoid Carcinoma","kind":"Disorder","source_path":"kb/disorders/Mucoepidermoid_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mucoepidermoid_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Mucoepidermoid_Carcinoma.html#dataset-geo-gse282430"}],"context_names":["Mucoepidermoid Carcinoma"],"disease_names":["Mucoepidermoid Carcinoma"],"disease_name":"Mucoepidermoid Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Mucoepidermoid_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mucoepidermoid_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Mucoepidermoid_Carcinoma.html#dataset-geo-gse282430"]},{"id":"dataset:geo:gse282464","accession":"geo:GSE282464","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE282464","title":"Molecular landscape of respiratory infection: A large-scale, multi-centre blood transcriptome dataset","alternate_titles":[],"description":"Respiratory infections pose significant challenges to global health, impacting millions of individuals annually. Understanding the molecular mechanisms underlying the pathogenicity of these infections is crucial for developing effective interventions. RNA sequencing provides insights into a patient’s global transcriptome changes, facilitating the identification of host gene signatures in response to infection and potential therapeutic targets.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[377],"sample_count":377,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40640204"],"publication_contexts":[{"context_id":"disorder:Seasonal_Coronavirus_Infection","publication":"PMID:40640204"}],"publication":"PMID:40640204","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40640204","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Seasonal Coronavirus Infection (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Seasonal_Coronavirus_Infection","name":"Seasonal Coronavirus Infection","kind":"Disorder","source_path":"kb/disorders/Seasonal_Coronavirus_Infection.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Seasonal_Coronavirus_Infection.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Seasonal_Coronavirus_Infection.html#dataset-geo-gse282464"}],"context_names":["Seasonal Coronavirus Infection"],"disease_names":["Seasonal Coronavirus Infection"],"disease_name":"Seasonal Coronavirus Infection","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Seasonal_Coronavirus_Infection.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Seasonal_Coronavirus_Infection.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Seasonal_Coronavirus_Infection.html#dataset-geo-gse282464"]},{"id":"dataset:geo:gse282618","accession":"geo:GSE282618","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE282618","title":"Multiomics Investigation of the Hypertensive Human Heart","alternate_titles":[],"description":"Biobanked, postmortem human heart tissue presents a unique opportunity to understand the pathogenesis of human cardiovascular disease risk factors through detailed multiomic analyses. We hypothesize that hypertension affects the cardiac transcriptome and cellular subtypes in a site-specific manner. We performed bulk and single-nucleus RNA-seq (snRNA-seq) on spatially distinct ventricular and atrial samples of postmortem hearts from donors with hypertension (n=3) and normotensive referents (n=2), using our rigorous cardiac dissection and preservation protocol.","alternate_descriptions":[],"data_types":["MULTI_OMICS"],"data_type_labels":["Multi Omics"],"data_type_label":"Multi Omics","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[10],"sample_count":10,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41036600"],"publication_contexts":[{"context_id":"disorder:Hypertensive_Heart_Disease","publication":"PMID:41036600"}],"publication":"PMID:41036600","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41036600","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Hypertensive Heart Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Hypertensive_Heart_Disease","name":"Hypertensive Heart Disease","kind":"Disorder","source_path":"kb/disorders/Hypertensive_Heart_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hypertensive_Heart_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertensive_Heart_Disease.html#dataset-geo-gse282618"}],"context_names":["Hypertensive Heart Disease"],"disease_names":["Hypertensive Heart Disease"],"disease_name":"Hypertensive Heart Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hypertensive_Heart_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hypertensive_Heart_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hypertensive_Heart_Disease.html#dataset-geo-gse282618"]},{"id":"dataset:geo:gse282859","accession":"geo:GSE282859","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE282859","title":"Absent in melanoma 2: a potent suppressor of retinal pigment epithelial-mesenchymal transition and experimental proliferative vitreoretinopathy","alternate_titles":[],"description":"Epithelial-to-mesenchymal transition (EMT) is a critical and complex process involved in normal embryonic development, tissue regeneration, and tumor progression. It also contributes to retinal diseases, such as age-related macular degeneration (AMD) and proliferative vitreoretinopathy (PVR). Although absent in melanoma 2 (AIM2) has been linked to inflammatory disorders, autoimmune diseases, and cancers, its role in the EMT of the retinal pigment epithelium (RPE-EMT) and retinal diseases remains unclear. The present study demonstrated that AIM2 functions as a potent suppressor of RPE cell proliferation and EMT to maintain retinal homeostasis.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39870644"],"publication_contexts":[{"context_id":"disorder:Proliferative_Vitreoretinopathy","publication":"PMID:39870644"}],"publication":"PMID:39870644","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39870644","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Proliferative Vitreoretinopathy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Proliferative_Vitreoretinopathy","name":"Proliferative Vitreoretinopathy","kind":"Disorder","source_path":"kb/disorders/Proliferative_Vitreoretinopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Proliferative_Vitreoretinopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Proliferative_Vitreoretinopathy.html#dataset-geo-gse282859"}],"context_names":["Proliferative Vitreoretinopathy"],"disease_names":["Proliferative Vitreoretinopathy"],"disease_name":"Proliferative Vitreoretinopathy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Proliferative_Vitreoretinopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Proliferative_Vitreoretinopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Proliferative_Vitreoretinopathy.html#dataset-geo-gse282859"]},{"id":"dataset:geo:gse282864","accession":"geo:GSE282864","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE282864","title":"Differential expression profiles of plasma exosomal microRNAs in obstructive sleep apnea patients","alternate_titles":[],"description":"Obstructive sleep apnea (OSA) is a prevalent respiratory disorder, with an estimated global prevalence of over one billion individuals, exhibiting a wide spectrum of severity. In this study, clinical data and whole blood samples were obtained from non-OSA individuals and OSA patients.we performed high-throughput sequencing to analyze differential expression of miRNAs between non-OSA exosomes (n=4) and OSA-Exos (n=6). This analysis identified 15 miRNAs exhibited significantly different expression levels between the two groups, with 7 upregulated and 8 downregulated in OSA-Exos compared to CON-Exos.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[10],"sample_count":10,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40505833"],"publication_contexts":[{"context_id":"disorder:Obstructive_Sleep_Apnea","publication":"PMID:40505833"}],"publication":"PMID:40505833","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40505833","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Obstructive Sleep Apnea (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Obstructive_Sleep_Apnea","name":"Obstructive Sleep Apnea","kind":"Disorder","source_path":"kb/disorders/Obstructive_Sleep_Apnea.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Obstructive_Sleep_Apnea.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Obstructive_Sleep_Apnea.html#dataset-geo-gse282864"}],"context_names":["Obstructive Sleep Apnea"],"disease_names":["Obstructive Sleep Apnea"],"disease_name":"Obstructive Sleep Apnea","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Obstructive_Sleep_Apnea.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Obstructive_Sleep_Apnea.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Obstructive_Sleep_Apnea.html#dataset-geo-gse282864"]},{"id":"dataset:geo:gse282913","accession":"geo:GSE282913","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE282913","title":"Gene Expression Analysis of CD4 T Cells in Autoimmune Pancreatitis: Treatment-Correlated Expression Profiles","alternate_titles":[],"description":"Introduction: Autoimmune pancreatitis (AIP) is a rare inflammatory disease characterized by elevated serum IgG4, pancreatic fibrosis, and immune cell infiltration. Prednisolone (PSL) effectively induces remission; however, high relapse rates after treatment cessation highlight the need for reliable biomarkers to predict long-term outcomes. While T cells, particularly regulatory T cells (Tregs) and Th2 cells, are implicated in AIP pathogenesis, comprehensive immune profiling has been limited. Methods: Peripheral blood CD4+ T cells were isolated from AIP patients in the active phase (aAIP, n = 8), remission phase (tAIP, n = 14), and healthy controls (HC, n = 23).","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[45],"sample_count":45,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Chronic Pancreatitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Chronic_Pancreatitis","name":"Chronic Pancreatitis","kind":"Disorder","source_path":"kb/disorders/Chronic_Pancreatitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Pancreatitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chronic_Pancreatitis.html#dataset-geo-gse282913"}],"context_names":["Chronic Pancreatitis"],"disease_names":["Chronic Pancreatitis"],"disease_name":"Chronic Pancreatitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chronic_Pancreatitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Pancreatitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chronic_Pancreatitis.html#dataset-geo-gse282913"]},{"id":"dataset:geo:gse283289","accession":"geo:GSE283289","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE283289","title":"Multi-omic sequencing reveals distinctive gene expression and epigenetic alterations associated with primary sclerosing cholangitis development in treatment-naïve paediatric ulcerative colitis","alternate_titles":[],"description":"Background: Primary sclerosing cholangitis (PSC) is a progressive cholestatic disease with up to 80% of patients also suffering from ulcerative colitis (PSC-UC). The difficulty in the diagnosis along with the increased risk for developing cancer represent a clinical challenge. Furthermore, the precise molecular factors regulating the phenotype of this disease subtype remain unknown. Methods: We applied methyl-capture sequencing and mRNA sequencing to colonic mucosal biopsies from 3 groups of treatment-naïve children at diagnosis from the DOCHAS study - UC (n=10), PSC-UC (n=10) and healthy controls(n=10).","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[25],"sample_count":25,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39944929"],"publication_contexts":[{"context_id":"disorder:Primary_Sclerosing_Cholangitis","publication":"PMID:39944929"},{"context_id":"disorder:Sclerosing_Cholangitis","publication":"PMID:39944929"}],"publication":"PMID:39944929","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39944929","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Primary Sclerosing Cholangitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.","Identified by GEO DataSets index search for Sclerosing Cholangitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Primary_Sclerosing_Cholangitis","name":"Primary Sclerosing Cholangitis","kind":"Disorder","source_path":"kb/disorders/Primary_Sclerosing_Cholangitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Primary_Sclerosing_Cholangitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Sclerosing_Cholangitis.html#dataset-geo-gse283289"},{"id":"disorder:Sclerosing_Cholangitis","name":"Sclerosing Cholangitis","kind":"Disorder","source_path":"kb/disorders/Sclerosing_Cholangitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sclerosing_Cholangitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Sclerosing_Cholangitis.html#dataset-geo-gse283289"}],"context_names":["Primary Sclerosing Cholangitis","Sclerosing Cholangitis"],"disease_names":["Primary Sclerosing Cholangitis","Sclerosing Cholangitis"],"disease_name":"Primary Sclerosing Cholangitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Primary_Sclerosing_Cholangitis.yaml","kb/disorders/Sclerosing_Cholangitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Primary_Sclerosing_Cholangitis.yaml","https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sclerosing_Cholangitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Primary_Sclerosing_Cholangitis.html#dataset-geo-gse283289","https://dismech.monarchinitiative.org/pages/disorders/Sclerosing_Cholangitis.html#dataset-geo-gse283289"]},{"id":"dataset:geo:gse283485","accession":"geo:GSE283485","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE283485","title":"G-quadruplexes regulate chromatin accessibility and gene expression in Bloom Syndrome [RNA-seq]","alternate_titles":[],"description":"Public RNA-seq series containing 24 samples from BLM-deficient and wild-type lymphoblastoid and fibroblast cell lines, with wild-type pyridostatin and vehicle perturbations. The associated preprint also reports ATAC-seq and G4 ChIP-seq; the data support an emerging regulatory hypothesis rather than a validated explanation for the clinical syndrome.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[24],"sample_count":24,"conditions":["BLM-deficient lymphoblastoid cell lines","Wild-type lymphoblastoid cell lines","BLM-deficient fibroblast cell lines","Wild-type fibroblast cell lines","Pyridostatin-treated wild-type cells","Vehicle-treated wild-type cells"],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:1058","label":"BLM","display_label":"BLM","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/1058"}],"genes":["BLM"],"platforms":[],"platform":null,"publications":["PMID:41867784"],"publication_contexts":[{"context_id":"disorder:Bloom_Syndrome","publication":"PMID:41867784"}],"publication":"PMID:41867784","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41867784","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:41867784","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41867784","reference_title":"G-quadruplexes regulate chromatin accessibility and gene expression in Bloom Syndrome.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Here, we profiled chromatin accessibility and gene expression using ATAC-seq and RNA-seq and mapped endogenous G4 by ChIP-seq in wild type (WT) and BS cell lines.","explanation":"The associated preprint describes the molecular profiling represented by the public series."}],"notes":[],"contexts":[{"id":"disorder:Bloom_Syndrome","name":"Bloom syndrome","kind":"Disorder","source_path":"kb/disorders/Bloom_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bloom_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Bloom_syndrome.html#dataset-geo-gse283485"}],"context_names":["Bloom syndrome"],"disease_names":["Bloom syndrome"],"disease_name":"Bloom syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Bloom_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bloom_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Bloom_syndrome.html#dataset-geo-gse283485"]},{"id":"dataset:geo:gse283826","accession":"geo:GSE283826","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE283826","title":"Single-cell RNA-sequencing analysis reveals the peripheral immune characteristics of patients with primary membranous nephropathy","alternate_titles":[],"description":"Primary Membranous Nephropathy (PMN) is characterized by dysregulated immune responses, with B and T cells playing critical roles in disease pathogenesis. While significant strides have been made in identifying specific autoantigens and leveraging monoclonal antibodies, the precise immunopathogenic mechanisms underlying immune cell involvement in PMN remain elusive. To comprehensively characterize the cellular, molecular, and immunological landscape, we employed single-cell RNA sequencing (scRNA-seq) on peripheral blood mononuclear cell samples (PBMC) obtained from 6 patients with PMN and 3 healthy controls (NC).We examined the heterogeneity and functional diversity of B cells in PMN.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[9],"sample_count":9,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40904455"],"publication_contexts":[{"context_id":"disorder:Membranous_Nephropathy","publication":"PMID:40904455"}],"publication":"PMID:40904455","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40904455","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Membranous nephropathy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Membranous_Nephropathy","name":"Membranous nephropathy","kind":"Disorder","source_path":"kb/disorders/Membranous_Nephropathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Membranous_Nephropathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Membranous_nephropathy.html#dataset-geo-gse283826"}],"context_names":["Membranous nephropathy"],"disease_names":["Membranous nephropathy"],"disease_name":"Membranous nephropathy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Membranous_Nephropathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Membranous_Nephropathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Membranous_nephropathy.html#dataset-geo-gse283826"]},{"id":"dataset:geo:gse283902","accession":"geo:GSE283902","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE283902","title":"Hydroxychloroquine prevents resistance and potentiates antitumor effect of SHP2 inhibition in NF1-associated Malignant Peripheral Nerve Sheath Tumors","alternate_titles":[],"description":"Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas and the primary cause of mortality in patients with neurofibromatosis type 1 (NF1). These malignancies develop within pre-existing benign lesions called plexiform neurofibromas (PNs). PNs are solely driven by biallelic NF1 loss eliciting RAS pathway activation and respond favorably to MEK inhibitor therapy. MPNSTs harbor additional mutations and respond poorly to MEK inhibition. Our analysis of genetically engineered and orthotopic patient-derived xenograft MPNST tumor models indicates that MEK inhibition has poor anti-tumor efficacy.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[31],"sample_count":31,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39793045"],"publication_contexts":[{"context_id":"disorder:Malignant_Peripheral_Nerve_Sheath_Tumor","publication":"PMID:39793045"}],"publication":"PMID:39793045","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39793045","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Malignant Peripheral Nerve Sheath Tumor (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Malignant_Peripheral_Nerve_Sheath_Tumor","name":"Malignant Peripheral Nerve Sheath Tumor","kind":"Disorder","source_path":"kb/disorders/Malignant_Peripheral_Nerve_Sheath_Tumor.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Malignant_Peripheral_Nerve_Sheath_Tumor.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Malignant_Peripheral_Nerve_Sheath_Tumor.html#dataset-geo-gse283902"}],"context_names":["Malignant Peripheral Nerve Sheath Tumor"],"disease_names":["Malignant Peripheral Nerve Sheath Tumor"],"disease_name":"Malignant Peripheral Nerve Sheath Tumor","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Malignant_Peripheral_Nerve_Sheath_Tumor.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Malignant_Peripheral_Nerve_Sheath_Tumor.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Malignant_Peripheral_Nerve_Sheath_Tumor.html#dataset-geo-gse283902"]},{"id":"dataset:geo:gse28405","accession":"geo:GSE28405","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE28405","title":"Genome-wide gene expression analysis of human whole-blood samples in  in response to dengue disease","alternate_titles":[],"description":"We looked at the whole-blood transcriptional profiling on dengue patients sampled within 72h of fever presentation and compared the signatures with autologous samples drawn at defervescence and convalescence and to control patients with fever of other etiology. Our data show that the early response in patients mimics those previously only described in vitro and suggests that this innate immune responses may initiate the later adaptive immune responses.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[119],"sample_count":119,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:21810247"],"publication_contexts":[{"context_id":"disorder:Dengue","publication":"PMID:21810247"}],"publication":"PMID:21810247","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/21810247","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Dengue (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Dengue","name":"Dengue","kind":"Disorder","source_path":"kb/disorders/Dengue.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dengue.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Dengue.html#dataset-geo-gse28405"}],"context_names":["Dengue"],"disease_names":["Dengue"],"disease_name":"Dengue","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Dengue.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dengue.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Dengue.html#dataset-geo-gse28405"]},{"id":"dataset:geo:gse284073","accession":"geo:GSE284073","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE284073","title":"Dysregulated cell states revealed by single-cell multiomics in mild malformations of cortical development with oligodendroglial hyperplasia in epilepsy","alternate_titles":[],"description":"Single-cell multiomic profiling of MOGHE tissue, mapping the dysregulated cell states behind the oligodendroglial clusters, heterotopic neurons, and white-matter hypomyelination that define the lesion.","alternate_descriptions":[],"data_types":["MULTI_OMICS"],"data_type_labels":["Multi Omics"],"data_type_label":"Multi Omics","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[8],"sample_count":8,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40293058"],"publication_contexts":[{"context_id":"disorder:SLC35A2-CDG","publication":"PMID:40293058"}],"publication":"PMID:40293058","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40293058","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Found by GEO DataSets search and verified against NCBI E-utilities on 2026-08-20. DIRECT relevance to the somatic-mosaic MOGHE subtype."],"contexts":[{"id":"disorder:SLC35A2-CDG","name":"SLC35A2-congenital disorder of glycosylation","kind":"Disorder","source_path":"kb/disorders/SLC35A2-CDG.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/SLC35A2-CDG.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/SLC35A2-congenital_disorder_of_glycosylation.html#dataset-geo-gse284073"}],"context_names":["SLC35A2-congenital disorder of glycosylation"],"disease_names":["SLC35A2-congenital disorder of glycosylation"],"disease_name":"SLC35A2-congenital disorder of glycosylation","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/SLC35A2-CDG.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/SLC35A2-CDG.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/SLC35A2-congenital_disorder_of_glycosylation.html#dataset-geo-gse284073"]},{"id":"dataset:geo:gse284273","accession":"geo:GSE284273","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE284273","title":"Dendritic cell iron overload exacerbates acetaminophen hepatotoxicity","alternate_titles":[],"description":"Liver immune homeostasis relies on the coordinated actions of various immune cells including dendritic cells (DCs), which exert regulatory roles in both innate and adaptive immunity. Various pieces of evidence demonstrate that the properties of immune cells are highly influenced by iron metabolism. However, the roles of iron metabolism on DC function remain poorly understood. Here, we show that mice with iron overload in DCs displayed worsening of liver injury and mortality in acetaminophen (APAP) -induced acute hepatitis. Enhanced neutrophil infiltration was observed in these mice during the progression of liver injury.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41120657"],"publication_contexts":[{"context_id":"disorder:Acetaminophen_Hepatotoxicity","publication":"PMID:41120657"}],"publication":"PMID:41120657","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41120657","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Acetaminophen Hepatotoxicity (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Acetaminophen_Hepatotoxicity","name":"Acetaminophen Hepatotoxicity","kind":"Disorder","source_path":"kb/disorders/Acetaminophen_Hepatotoxicity.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Acetaminophen_Hepatotoxicity.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Acetaminophen_Hepatotoxicity.html#dataset-geo-gse284273"}],"context_names":["Acetaminophen Hepatotoxicity"],"disease_names":["Acetaminophen Hepatotoxicity"],"disease_name":"Acetaminophen Hepatotoxicity","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Acetaminophen_Hepatotoxicity.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Acetaminophen_Hepatotoxicity.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Acetaminophen_Hepatotoxicity.html#dataset-geo-gse284273"]},{"id":"dataset:geo:gse284479","accession":"geo:GSE284479","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE284479","title":"Altered thymopoiesis in thymoma is associated with defects in negative selection machinery and decreased Treg abundance","alternate_titles":[],"description":"Thymomas are rare thymic epithelial tumors harboring a high but variable proportion of lymphocytes without obvious function. Auto-immunity is present in one third of patients at diagnosis. Herein, we performed a phenotypic, scRNAseq, and spatial analysis of both the T cells and tumoral cells. All stages of T cell development -from immature to mature- were present in the tumor suggesting active thymopoiesis in thymoma. However, multiple approaches suggest a maturation blockade at the DN-DP stages. In the mature T cell compartment, the frequency of Tregs was strongly decreased.","alternate_descriptions":[],"data_types":["MULTI_OMICS"],"data_type_labels":["Multi Omics"],"data_type_label":"Multi Omics","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[53],"sample_count":53,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41143696"],"publication_contexts":[{"context_id":"disorder:Thymoma","publication":"PMID:41143696"}],"publication":"PMID:41143696","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41143696","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Thymoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Thymoma","name":"Thymoma","kind":"Disorder","source_path":"kb/disorders/Thymoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Thymoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Thymoma.html#dataset-geo-gse284479"}],"context_names":["Thymoma"],"disease_names":["Thymoma"],"disease_name":"Thymoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Thymoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Thymoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Thymoma.html#dataset-geo-gse284479"]},{"id":"dataset:geo:gse284678","accession":"geo:GSE284678","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE284678","title":"UBE3A reinstatement restores behavior and proteome in an Angelman syndrome mouse model of imprinting defects","alternate_titles":[],"description":"Mouse RNA-seq resource from an imprinting-center Angelman model (mICD/UPD relevant) with UBE3A reinstatement interventions to evaluate rescue of molecular and behavioral phenotypes.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"house mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[14],"sample_count":14,"conditions":["mICD Angelman model mice","UBE3A reinstatement conditions","control mice"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40877933"],"publication_contexts":[{"context_id":"disorder:Angelman_Syndrome","publication":"PMID:40877933"}],"publication":"PMID:40877933","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40877933","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE284678","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE284678","reference_title":"UBE3A reinstatement restores behavior and proteome in an Angelman syndrome mouse model of imprinting defects","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"mICD mice showed significant reduction in UBE3A protein, bi-allelic expression of Ube3a-ATS and Mkrn3-Snord115 gene cluster, leading to robust AS behavioral deficits and proteome alterations similar to Ube3aKO mice.","explanation":"Supports utility of this model for transcriptomic interrogation of imprinting-related Angelman pathophysiology."},{"reference":"GEO:GSE284678","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE284678","reference_title":"UBE3A reinstatement restores behavior and proteome in an Angelman syndrome mouse model of imprinting defects","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"Genetic UBE3A overexpression in mICD mice, mimicking therapeutic strategies that effectively activate the biallelic silenced Ube3a gene, resulted in a complete rescue of all behavioral and proteome alterations.","explanation":"Adds mechanistic rescue context relevant to disease-modifying therapy modeling."}],"notes":[],"contexts":[{"id":"disorder:Angelman_Syndrome","name":"Angelman Syndrome","kind":"Disorder","source_path":"kb/disorders/Angelman_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Angelman_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Angelman_Syndrome.html#dataset-geo-gse284678"}],"context_names":["Angelman Syndrome"],"disease_names":["Angelman Syndrome"],"disease_name":"Angelman Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Angelman_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Angelman_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Angelman_Syndrome.html#dataset-geo-gse284678"]},{"id":"dataset:geo:gse285009","accession":"geo:GSE285009","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE285009","title":"Mechanistic Investigation of Five Small-Molecule Inhibitors in the Treatment of Pemphigus Vulgaris via RNA-Seq Analysis","alternate_titles":[],"description":"Pemphigus vulgaris (PV) is an autoimmune disorder characterized by autoantibodies (AAbs) against Desmoglein 1 (DSG1) and Desmoglein 3 (DSG3) on keratinocytes, resulting in compromised cell-cell adhesion and epidermal blistering. To explore potential therapeutic targets, five small-molecule inhibitors, A66 (PI3Kα inhibitor), BIRB796 (p38 MAPK inhibitor), GW441756 (TrkA inhibitor), Selumetinib (MEK1 inhibitor), and Vandetanib (VEGFR2 inhibitor) were selected through a screen identifying compounds that reduce split formation in a human skin organ culture (HSOC) model.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[34],"sample_count":34,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Pemphigus Vulgaris (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Pemphigus_Vulgaris","name":"Pemphigus Vulgaris","kind":"Disorder","source_path":"kb/disorders/Pemphigus_Vulgaris.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pemphigus_Vulgaris.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pemphigus_Vulgaris.html#dataset-geo-gse285009"}],"context_names":["Pemphigus Vulgaris"],"disease_names":["Pemphigus Vulgaris"],"disease_name":"Pemphigus Vulgaris","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Pemphigus_Vulgaris.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pemphigus_Vulgaris.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Pemphigus_Vulgaris.html#dataset-geo-gse285009"]},{"id":"dataset:geo:gse285196","accession":"geo:GSE285196","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE285196","title":"Pathogenesis of Graves' Disease Using Single-Cell Sequencing with Thyroid Autoantigens Peptides Stimulation in B Cells","alternate_titles":[],"description":"We used the latest technology, BD Rhapsody, to analyze BCR of PBMCs and intrathyroidal blood mononuclear cells from patients with Graves' disease at the single-cell level.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[10],"sample_count":10,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40710355"],"publication_contexts":[{"context_id":"disorder:Graves_Disease","publication":"PMID:40710355"}],"publication":"PMID:40710355","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40710355","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Graves' Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Graves_Disease","name":"Graves' Disease","kind":"Disorder","source_path":"kb/disorders/Graves_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Graves_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Graves'_Disease.html#dataset-geo-gse285196"}],"context_names":["Graves' Disease"],"disease_names":["Graves' Disease"],"disease_name":"Graves' Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Graves_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Graves_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Graves'_Disease.html#dataset-geo-gse285196"]},{"id":"dataset:geo:gse285203","accession":"geo:GSE285203","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE285203","title":"Transcriptome analyses of human corneal endothelial cell lines derived from patients with Fuchs Endothelial Corneal Dystrophy","alternate_titles":[],"description":"We report differential gene expression profiles of the corneal endothelial cells from Fuchs dystrophy patients with or without the TCF4 gene mutation","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[11],"sample_count":11,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41298634"],"publication_contexts":[{"context_id":"disorder:Fuchs_Endothelial_Corneal_Dystrophy","publication":"PMID:41298634"}],"publication":"PMID:41298634","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41298634","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Fuchs Endothelial Corneal Dystrophy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Fuchs_Endothelial_Corneal_Dystrophy","name":"Fuchs Endothelial Corneal Dystrophy","kind":"Disorder","source_path":"kb/disorders/Fuchs_Endothelial_Corneal_Dystrophy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fuchs_Endothelial_Corneal_Dystrophy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Fuchs_Endothelial_Corneal_Dystrophy.html#dataset-geo-gse285203"}],"context_names":["Fuchs Endothelial Corneal Dystrophy"],"disease_names":["Fuchs Endothelial Corneal Dystrophy"],"disease_name":"Fuchs Endothelial Corneal Dystrophy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Fuchs_Endothelial_Corneal_Dystrophy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fuchs_Endothelial_Corneal_Dystrophy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Fuchs_Endothelial_Corneal_Dystrophy.html#dataset-geo-gse285203"]},{"id":"dataset:geo:gse285347","accession":"geo:GSE285347","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE285347","title":"Epigenetic biomarker discovery in IgA nephropathy: chromatin openness analysis of circulating CD8+ T cells using ATAC-Seq","alternate_titles":[],"description":"Chromatin openess plays a critical role in understanding epigenetic regulation in disease states. Using ATAC-seq, we profiled circulating CD8+ T cells from IgA nephropathy (IgAN) patients to identify biomarkers distinguishing early and late disease stages. A total of 279 differential ATAC peaks were identified, with 122 selected as biomarkers based on fold change (>2) and statistical significance (P < 0.05). These biomarkers exhibited distinct chromatin accessibility patterns, highlighting differential regulatory mechanisms. Combining multiple biomarkers through weighted scoring enhanced predictive accuracy, with ROC analysis confirming their diagnostic potential.","alternate_descriptions":[],"data_types":["ATAC_SEQ"],"data_type_labels":["Assay for transposase-accessible chromatin sequencing"],"data_type_label":"Assay for transposase-accessible chromatin sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[17],"sample_count":17,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41466033"],"publication_contexts":[{"context_id":"disorder:IgA_Nephropathy","publication":"PMID:41466033"}],"publication":"PMID:41466033","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41466033","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for IgA Nephropathy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:IgA_Nephropathy","name":"IgA Nephropathy","kind":"Disorder","source_path":"kb/disorders/IgA_Nephropathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/IgA_Nephropathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/IgA_Nephropathy.html#dataset-geo-gse285347"}],"context_names":["IgA Nephropathy"],"disease_names":["IgA Nephropathy"],"disease_name":"IgA Nephropathy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/IgA_Nephropathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/IgA_Nephropathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/IgA_Nephropathy.html#dataset-geo-gse285347"]},{"id":"dataset:geo:gse286067","accession":"geo:GSE286067","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE286067","title":"Autism spectrum disorder associated chromatin modifiers converge on transcription with sex-specific regulatory signatures","alternate_titles":[],"description":"We sought to understand the transcriptional disruptions and functional impacts of the loss of 9 autism spectrum disorder (ASD) risk genes that encode transcriptional regulators in neurons. In addition to understanding how these signature converge or diverge, we aimed to study how sex could modulate these consequences.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[66],"sample_count":66,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40196547"],"publication_contexts":[{"context_id":"disorder:Autism_Spectrum_Disorder","publication":"PMID:40196547"}],"publication":"PMID:40196547","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40196547","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Autism Spectrum Disorder (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. 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This is physiology rather than poisoning: it reports that cells make cyanide at low concentrations where it acts as a gasotransmitter, and that the same molecule impairs bioenergetics at high concentrations. It is included here because the dose-dependent flip is the biological context for the toxic node in this entry, and because it profiles the detoxifying enzyme TST that the genetic section curates as a modifier.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:12388","label":"TST","display_label":"TST","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/12388"}],"genes":["TST"],"platforms":[],"platform":null,"publications":["PMID:40033006"],"publication_contexts":[{"context_id":"disorder:Cyanide_Poisoning","publication":"PMID:40033006"}],"publication":"PMID:40033006","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40033006","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE286106","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE286106","reference_title":null,"supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"When generated at a specific rate, cyanide exerts stimulatory effects on mitochondrial bioenergetics, cell metabolism, and cell proliferation, but impairs cellular bioenergetics at high concentrations.","explanation":"The repository summary states the concentration-dependent reversal that separates endogenous cyanide signalling from the bioenergetic failure this entry models."}],"notes":["A GENE_ONLY candidate by the discovery tool's classification, retained after manual triage because its subject is cyanide itself rather than an unrelated disease that happens to express TST."],"contexts":[{"id":"disorder:Cyanide_Poisoning","name":"Cyanide Poisoning","kind":"Disorder","source_path":"kb/disorders/Cyanide_Poisoning.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cyanide_Poisoning.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cyanide_Poisoning.html#dataset-geo-gse286106"}],"context_names":["Cyanide Poisoning"],"disease_names":["Cyanide Poisoning"],"disease_name":"Cyanide Poisoning","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cyanide_Poisoning.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cyanide_Poisoning.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cyanide_Poisoning.html#dataset-geo-gse286106"]},{"id":"dataset:geo:gse287118","accession":"geo:GSE287118","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE287118","title":"Multiomics identifies unique modulators of calf muscle pathophysiology in peripheral artery disease and chronic kidney disease","alternate_titles":[],"description":"This project aimed to map transcriptome changes in the skeletal muscle of patients with and without PAD (peripheral artery disease) and CKD (chronic kidney disease)","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[86],"sample_count":86,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39963788"],"publication_contexts":[{"context_id":"disorder:Peripheral_Artery_Disease","publication":"PMID:39963788"}],"publication":"PMID:39963788","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39963788","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Peripheral Artery Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Peripheral_Artery_Disease","name":"Peripheral Artery Disease","kind":"Disorder","source_path":"kb/disorders/Peripheral_Artery_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Peripheral_Artery_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Peripheral_Artery_Disease.html#dataset-geo-gse287118"}],"context_names":["Peripheral Artery Disease"],"disease_names":["Peripheral Artery Disease"],"disease_name":"Peripheral Artery Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Peripheral_Artery_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Peripheral_Artery_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Peripheral_Artery_Disease.html#dataset-geo-gse287118"]},{"id":"dataset:geo:gse287223","accession":"geo:GSE287223","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE287223","title":"Circulating microRNAs as predictive biomarkers for progestin treatment response in endometriosis patients","alternate_titles":[],"description":"Total RNA was extracted from 400 ul of serum with the miRNeasy Serum/Plasma advanced Kit (Qiagen) and quantified using the Qubit microRNA assay kit (Thermo Fisher Scientific). cDNA templates were prepared using the TaqMan Advanced miRNA cDNA Synthesis Kit (Thermo Fisher Scientific), starting from 10 ng of RNA. RT-qPCR carried out on a QuantStudio 12K Flex (Applied Biosystems) using the TaqMan OpenArray miRNA panel.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[84],"sample_count":84,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Endometriosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Endometriosis","name":"Endometriosis","kind":"Disorder","source_path":"kb/disorders/Endometriosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Endometriosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Endometriosis.html#dataset-geo-gse287223"}],"context_names":["Endometriosis"],"disease_names":["Endometriosis"],"disease_name":"Endometriosis","same_context_model_ids":["model:kb/disorders/Endometriosis.yaml:Droplet-based microfluidic protease-activity profiling platform (PrAMA; MIT Griffith/Han)"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Endometriosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Endometriosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Endometriosis.html#dataset-geo-gse287223"]},{"id":"dataset:geo:gse287744","accession":"geo:GSE287744","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE287744","title":"Neurocellular stress response to Mojave Type A Rattlesnake venom: A study of molecular mechanisms using a human iPSC-derived neural stem cell model","alternate_titles":[],"description":"The Mojave rattlesnake (Crotalus scutulatus scutulatus) is classified as the “highest medically important” snake in the risk categories in the United States. Although responsible for fewer snakebite envenomations and deaths compared to other species, Mojave rattlesnake venom is poorly characterized and shows significant geographical variability. The venom of Type A animals primarily contains the β-neurotoxin referred to as Mojave Toxin (MTX), which is responsible for the neurotoxic effects that make bites from this snake particularly feared.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[24],"sample_count":24,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40149917"],"publication_contexts":[{"context_id":"disorder:Snakebite_Envenoming","publication":"PMID:40149917"}],"publication":"PMID:40149917","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40149917","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Snakebite envenoming (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Snakebite_Envenoming","name":"Snakebite envenoming","kind":"Disorder","source_path":"kb/disorders/Snakebite_Envenoming.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Snakebite_Envenoming.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Snakebite_envenoming.html#dataset-geo-gse287744"}],"context_names":["Snakebite envenoming"],"disease_names":["Snakebite envenoming"],"disease_name":"Snakebite envenoming","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Snakebite_Envenoming.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Snakebite_Envenoming.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Snakebite_envenoming.html#dataset-geo-gse287744"]},{"id":"dataset:geo:gse287906","accession":"geo:GSE287906","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE287906","title":"Common and Distinct Circulating MicroRNAs Across Four Neurovascular Disorders","alternate_titles":[],"description":"Background: Familial cerebral cavernous malformations (FCCM), Sturge-Weber Syndrome (SWS), and hereditary hemorrhagic telangiectasia with brain arteriovenous malformations (HHT) are neurovascular disorders driven by genetic mutations. Cerebral microbleeds (CMBs) are primarily associated with the aging process with less known about genetic drivers. This study hypothesizes that common and distinct circulating microribonucleic acids (miRNAs) reflect shared and different pathobiology and can serve as potential diagnostic and mechanistic biomarkers.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[36],"sample_count":36,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40800603"],"publication_contexts":[{"context_id":"disorder:Sturge-Weber_Syndrome","publication":"PMID:40800603"}],"publication":"PMID:40800603","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40800603","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Sturge-Weber Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Sturge-Weber_Syndrome","name":"Sturge-Weber Syndrome","kind":"Disorder","source_path":"kb/disorders/Sturge-Weber_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sturge-Weber_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Sturge-Weber_Syndrome.html#dataset-geo-gse287906"}],"context_names":["Sturge-Weber Syndrome"],"disease_names":["Sturge-Weber Syndrome"],"disease_name":"Sturge-Weber Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Sturge-Weber_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sturge-Weber_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Sturge-Weber_Syndrome.html#dataset-geo-gse287906"]},{"id":"dataset:geo:gse288082","accession":"geo:GSE288082","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE288082","title":"Modeling long QT syndrome using gene-edited pigs","alternate_titles":[],"description":"Bulk RNA-seq dataset from left ventricular tissue of a KCNH2-mutant miniature pig model developed to recapitulate LQT2-associated electrophysiology and remodeling.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9823","label":"Sus scrofa","display_label":"pig","url":"http://purl.obolibrary.org/obo/NCBITaxon_9823"}],"organism_labels":["Sus scrofa"],"organism_label":"Sus scrofa","sample_types":[{"id":"UBERON:0002084","label":"heart left ventricle","display_label":"left ventricular myocardium","url":"http://purl.obolibrary.org/obo/UBERON_0002084"}],"sample_type_labels":["heart left ventricle"],"sample_counts":[8],"sample_count":8,"conditions":["KCNH2-mutant long QT syndrome type 2 miniature pig","wild-type left ventricular control tissue"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE288082","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE288082","reference_title":"Modeling long QT syndrome using gene-edited pigs","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"To explore the mechanism underlying mutation of KCNH2 caused LQT, we compared the transcriptomes of KCNH2-mut pigs and WT controls","explanation":"This supports GSE288082 as a disease-relevant large-animal transcriptomic dataset for KCNH2-mediated long QT syndrome biology."}],"notes":["GEO summary describes transcriptomic comparison of KCNH2-mutant versus wild type ventricular tissue in a large-animal LQT2 model."],"contexts":[{"id":"disorder:Long_QT_Syndrome","name":"Familial Long QT Syndrome","kind":"Disorder","source_path":"kb/disorders/Long_QT_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Long_QT_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Familial_Long_QT_Syndrome.html#dataset-geo-gse288082"}],"context_names":["Familial Long QT Syndrome"],"disease_names":["Familial Long QT Syndrome"],"disease_name":"Familial Long QT Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Long_QT_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Long_QT_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Familial_Long_QT_Syndrome.html#dataset-geo-gse288082"]},{"id":"dataset:geo:gse288205","accession":"geo:GSE288205","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE288205","title":"The m6A demethylase FTO regulates TNF-α expression in human macrophages following Toxoplasma gondii infection","alternate_titles":[],"description":"Methylation profiling of human macrophages after Toxoplasma gondii infection, relevant to the macrophage host-response arm of the Interferon-Gamma-Dependent Cell-Autonomous Immune Control node.","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[8],"sample_count":8,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40663568"],"publication_contexts":[{"context_id":"disorder:Toxoplasmosis","publication":"PMID:40663568"}],"publication":"PMID:40663568","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40663568","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified via `just discover-datasets Toxoplasmosis` (DIRECT relevance tier) and confirmed with `just verify-datasets`. No evidence block: a bulk-discovered accession has no abstract quote to anchor an evidence item."],"contexts":[{"id":"disorder:Toxoplasmosis","name":"Toxoplasmosis","kind":"Disorder","source_path":"kb/disorders/Toxoplasmosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Toxoplasmosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Toxoplasmosis.html#dataset-geo-gse288205"}],"context_names":["Toxoplasmosis"],"disease_names":["Toxoplasmosis"],"disease_name":"Toxoplasmosis","same_context_model_ids":["model:kb/disorders/Toxoplasmosis.yaml:Human cell culture single-cell transcriptomics of ROP/GRA effector injection","model:kb/disorders/Toxoplasmosis.yaml:Stress-induced bradyzoite differentiation in cell culture"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Toxoplasmosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Toxoplasmosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Toxoplasmosis.html#dataset-geo-gse288205"]},{"id":"dataset:geo:gse288459","accession":"geo:GSE288459","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE288459","title":"Single Cell Transcriptome Signatures of Sarcoidosis in Lung Immune Cell Populations","alternate_titles":[],"description":"Rationale: To identify cell specific molecular changes associated with sarcoidosis risk and progression, we aimed to characterize the cellular composition, gene expression patterns, and cell-cell interactions in BAL cells from patients with sarcoidosis (both progressive and non-progressive) and healthy controls. Methods: Single cell RNA-seq data were collected on 12 sarcoidosis and 4 control participants. We combined scRNA-seq data from these participants with our previously collected data on 4 sarcoidosis and 10 control participants for a final sample size of 16 sarcoidosis cases (8 progressive and 8 non-progressive) and 14 controls.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[16],"sample_count":16,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42273700"],"publication_contexts":[{"context_id":"disorder:Sarcoidosis","publication":"PMID:42273700"}],"publication":"PMID:42273700","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42273700","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Sarcoidosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Sarcoidosis","name":"Sarcoidosis","kind":"Disorder","source_path":"kb/disorders/Sarcoidosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sarcoidosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Sarcoidosis.html#dataset-geo-gse288459"}],"context_names":["Sarcoidosis"],"disease_names":["Sarcoidosis"],"disease_name":"Sarcoidosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Sarcoidosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sarcoidosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Sarcoidosis.html#dataset-geo-gse288459"]},{"id":"dataset:geo:gse288492","accession":"geo:GSE288492","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE288492","title":"Transcriptome Response to Autoantibodies in Human Primary Epidermis Keratinocyte Model for Pemphgus Vulgaris","alternate_titles":[],"description":"Pemphigus vulgaris (PV) is an autoimmune disease caused by autoantibodies (AAbs) targeting Desmoglein 1 (DSG1) or Desmoglein 3 (DSG3) on keratinocytes, leading to disrupted cell-cell adhesion and epidermal blistering. To investigate the early signaling events triggered by AAb binding, we examined transcriptomic responses in a human primary epidermis keratinocyte (HPEK) model for PV. After incubating the single-chain variable fragment (scFv) PX43, which targets DSG1 and DSG3, and human IgG as control for 5h, 10h and 24h, differentially expressed genes (DEGs) and regulated pathways was analyzed using DESeq2 and pathway enrichment analysis.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[24],"sample_count":24,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Pemphigus Vulgaris (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Pemphigus_Vulgaris","name":"Pemphigus Vulgaris","kind":"Disorder","source_path":"kb/disorders/Pemphigus_Vulgaris.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pemphigus_Vulgaris.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pemphigus_Vulgaris.html#dataset-geo-gse288492"}],"context_names":["Pemphigus Vulgaris"],"disease_names":["Pemphigus Vulgaris"],"disease_name":"Pemphigus Vulgaris","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Pemphigus_Vulgaris.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pemphigus_Vulgaris.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Pemphigus_Vulgaris.html#dataset-geo-gse288492"]},{"id":"dataset:geo:gse288499","accession":"geo:GSE288499","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE288499","title":"Mutation in Wdr45 leads to early motor dysfunction and widespread aberrant axon terminals in a beta-propeller protein associated neurodegeneration (BPAN) patient-inspired mouse model","alternate_titles":[],"description":"Beta-propeller Protein Associated Neurodegeneration (BPAN) is a devastating neurodevelopmental and neurodegenerative disease linked to variants in WDR45. Currently, there is no cure or disease altering treatment for this disease. This is, in part, due to a lack of insight into early phenotypes of BPAN progression and WDR45’s role in establishing and maintaining neurological function. Here we generated and characterized a mouse model bearing a c52C>T BPAN patient variant in Wdr45. We show this mutation ablates WDR45 protein expression and alters autophagy in the brain.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[8],"sample_count":8,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40092065"],"publication_contexts":[{"context_id":"disorder:Neurodegeneration_With_Brain_Iron_Accumulation","publication":"PMID:40092065"}],"publication":"PMID:40092065","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40092065","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Neurodegeneration With Brain Iron Accumulation (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Neurodegeneration_With_Brain_Iron_Accumulation","name":"Neurodegeneration With Brain Iron Accumulation","kind":"Disorder","source_path":"kb/disorders/Neurodegeneration_With_Brain_Iron_Accumulation.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Neurodegeneration_With_Brain_Iron_Accumulation.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Neurodegeneration_With_Brain_Iron_Accumulation.html#dataset-geo-gse288499"}],"context_names":["Neurodegeneration With Brain Iron Accumulation"],"disease_names":["Neurodegeneration With Brain Iron Accumulation"],"disease_name":"Neurodegeneration With Brain Iron Accumulation","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Neurodegeneration_With_Brain_Iron_Accumulation.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Neurodegeneration_With_Brain_Iron_Accumulation.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Neurodegeneration_With_Brain_Iron_Accumulation.html#dataset-geo-gse288499"]},{"id":"dataset:geo:gse288567","accession":"geo:GSE288567","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE288567","title":"Macrophages orchestrate elimination of Shigella from the intestinal epithelial cell niche via TLR-induced IL-12 and IFN-γ","alternate_titles":[],"description":"Gene expression profiling of macrophage-mediated immune response to Shigella infection. Characterizes the role of macrophage-derived IL-12 and IFN-γ in controlling bacterial survival in intestinal epithelial cells during early shigellosis infection.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"Homo sapiens","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"CL:0000235","label":"macrophage","display_label":"macrophage","url":"http://purl.obolibrary.org/obo/CL_0000235"},{"id":"CL:0002669","label":"intestinal epithelial cell","display_label":"intestinal epithelial cell","url":"http://purl.obolibrary.org/obo/CL_0002669"}],"sample_type_labels":["macrophage","intestinal epithelial cell"],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40885187"],"publication_contexts":[{"context_id":"disorder:Shigellosis","publication":"PMID:40885187"}],"publication":"PMID:40885187","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40885187","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":[],"contexts":[{"id":"disorder:Shigellosis","name":"Shigellosis","kind":"Disorder","source_path":"kb/disorders/Shigellosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Shigellosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Shigellosis.html#dataset-geo-gse288567"}],"context_names":["Shigellosis"],"disease_names":["Shigellosis"],"disease_name":"Shigellosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Shigellosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Shigellosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Shigellosis.html#dataset-geo-gse288567"]},{"id":"dataset:geo:gse288693","accession":"geo:GSE288693","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE288693","title":"Chromatin interaction maps of human arterioles reveal new mechanisms for the genetic regulation of blood pressure [RRBS]","alternate_titles":[],"description":"Arterioles are small blood vessels located just upstream of capillaries in nearly all tissues. The constriction and dilation of arterioles regulate tissue perfusion and are primary determinants of systemic blood pressure (BP). Abnormalities in arterioles are central to the development of major diseases such as hypertension, stroke, and microvascular complications of diabetes. Despite the broad and essential role of arterioles in physiology and disease, current knowledge of the functional genomics of arterioles is largely absent, partly because it is challenging to obtain and analyze human arteriole samples.","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40675959"],"publication_contexts":[{"context_id":"disorder:Essential_Hypertension","publication":"PMID:40675959"}],"publication":"PMID:40675959","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40675959","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Essential Hypertension (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Essential_Hypertension","name":"Essential Hypertension","kind":"Disorder","source_path":"kb/disorders/Essential_Hypertension.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Essential_Hypertension.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Essential_Hypertension.html#dataset-geo-gse288693"}],"context_names":["Essential Hypertension"],"disease_names":["Essential Hypertension"],"disease_name":"Essential Hypertension","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Essential_Hypertension.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Essential_Hypertension.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Essential_Hypertension.html#dataset-geo-gse288693"]},{"id":"dataset:geo:gse288887","accession":"geo:GSE288887","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE288887","title":"Pulmonary osteoclast-like cells in silica induced pulmonary fibrosis","alternate_titles":[],"description":"The pathophysiology of silicosis is poorly understood, limiting development of therapies for those who have been exposed to the respirable particle. We explored mechanisms of silica-induced pulmonary fibrosis in human lung samples collected from patients with occupational exposure to silica and in a longitudinal mouse model of silicosis using multiple modalities including whole-lung single-cell RNA sequencing and histological, biochemical, and physiologic assessments.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[10],"sample_count":10,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:38985878"],"publication_contexts":[{"context_id":"disorder:Silicosis","publication":"PMID:38985878"}],"publication":"PMID:38985878","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38985878","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Silicosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Silicosis","name":"Silicosis","kind":"Disorder","source_path":"kb/disorders/Silicosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Silicosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Silicosis.html#dataset-geo-gse288887"}],"context_names":["Silicosis"],"disease_names":["Silicosis"],"disease_name":"Silicosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Silicosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Silicosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Silicosis.html#dataset-geo-gse288887"]},{"id":"dataset:geo:gse288958","accession":"geo:GSE288958","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE288958","title":"Inhibiting EZH2 complements steroid effects in Duchenne muscular dystrophy","alternate_titles":[],"description":"Duchenne muscular dystrophy (DMD) is a devastating X-linked disorder caused by mutations in the dystrophin gene. Despite recent advances in understanding the disease etiology and applying emerging treatment methodologies, glucocorticoid derivatives remain the only general therapeutic option that can slow disease development. However, the precise molecular mechanism of glucocorticoid action remains unclear, and there is still need for additional remedies to complement the treatment. Here, using single-nucleus RNA-sequencing and spatial transcriptome analyses of human and mouse muscles, we investigated pathogenic features in DMD patients and palliative effects of glucocorticoids.","alternate_descriptions":[],"data_types":["MULTI_OMICS"],"data_type_labels":["Multi Omics"],"data_type_label":"Multi Omics","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[11],"sample_count":11,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40085707"],"publication_contexts":[{"context_id":"disorder:Duchenne_Muscular_Dystrophy","publication":"PMID:40085707"}],"publication":"PMID:40085707","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40085707","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Duchenne Muscular Dystrophy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Duchenne_Muscular_Dystrophy","name":"Duchenne Muscular Dystrophy","kind":"Disorder","source_path":"kb/disorders/Duchenne_Muscular_Dystrophy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Duchenne_Muscular_Dystrophy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Duchenne_Muscular_Dystrophy.html#dataset-geo-gse288958"}],"context_names":["Duchenne Muscular Dystrophy"],"disease_names":["Duchenne Muscular Dystrophy"],"disease_name":"Duchenne Muscular Dystrophy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Duchenne_Muscular_Dystrophy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Duchenne_Muscular_Dystrophy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Duchenne_Muscular_Dystrophy.html#dataset-geo-gse288958"]},{"id":"dataset:geo:gse289185","accession":"geo:GSE289185","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE289185","title":"Safety and efficacy of neoadjuvant radiotherapy and immunotherapy in the treatment of esophageal squamous cell carcinoma","alternate_titles":[],"description":"Bulk transcriptomic resource from ESCC tumors sampled before and after neoadjuvant radiotherapy and immunotherapy, linked to PD-L1 analysis and pathologic response.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":["pre-treatment esophageal squamous cell carcinoma","post-neoadjuvant radiotherapy and immunotherapy esophageal squamous cell carcinoma"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE289185","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE289185","reference_title":"Safety and efficacy of neoadjuvant radiotherapy and immunotherapy in the treatment of esophageal squamous cell carcinoma","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"Additionally, paraffin-embedded tissue sections obtained before and after neoadjuvant NRIT were subjected to whole-exome sequencing, transcriptome sequencing, and immunohistochemistry (IHC) for programmed death-ligand 1 (PD-L1) analysis.","explanation":"Establishes the paired pre- and post-treatment sampling and the transcriptome and PD-L1 assays behind this record, which is what makes it a clinically linked ESCC resource spanning neoadjuvant immunotherapy exposure."}],"notes":[],"contexts":[{"id":"disorder:Esophageal_Squamous_Cell_Carcinoma","name":"Esophageal Squamous Cell Carcinoma","kind":"Disorder","source_path":"kb/disorders/Esophageal_Squamous_Cell_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Esophageal_Squamous_Cell_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Esophageal_Squamous_Cell_Carcinoma.html#dataset-geo-gse289185"}],"context_names":["Esophageal Squamous Cell Carcinoma"],"disease_names":["Esophageal Squamous Cell Carcinoma"],"disease_name":"Esophageal Squamous Cell Carcinoma","same_context_model_ids":["model:kb/disorders/Esophageal_Squamous_Cell_Carcinoma.yaml:Patient-derived esophageal squamous cell carcinoma organoid library (ESCCO)"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Esophageal_Squamous_Cell_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Esophageal_Squamous_Cell_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Esophageal_Squamous_Cell_Carcinoma.html#dataset-geo-gse289185"]},{"id":"dataset:geo:gse289237","accession":"geo:GSE289237","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE289237","title":"Effect of overexpression of HMGA2 in human chondrosarcoma SW1353 cell line overexpression and control cells.","alternate_titles":[],"description":"Chondrosarcoma (CHS) is a malignant bone tumour resistant to adjuvant treatment, with high-grade patients suffering an unfavorable prognosis. The high mobility group A2 (HMGA2) protein is a non‑histone architectural transcription factor influencing a variety of biological processes, including the cell cycle process, DNA damage repair process, apoptosis, senescence and epithelial‑mesenchymal transition. We here aimed to investigate the role of HMGA2 in CHS.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41964890"],"publication_contexts":[{"context_id":"disorder:Chondrosarcoma","publication":"PMID:41964890"}],"publication":"PMID:41964890","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41964890","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Chondrosarcoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Chondrosarcoma","name":"Chondrosarcoma","kind":"Disorder","source_path":"kb/disorders/Chondrosarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chondrosarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chondrosarcoma.html#dataset-geo-gse289237"}],"context_names":["Chondrosarcoma"],"disease_names":["Chondrosarcoma"],"disease_name":"Chondrosarcoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chondrosarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chondrosarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chondrosarcoma.html#dataset-geo-gse289237"]},{"id":"dataset:geo:gse289534","accession":"geo:GSE289534","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE289534","title":"A hexamer tandem repeat RNA embedded within an SVA retrotransposon drives R-loop formation and neurodegeneration","alternate_titles":[],"description":"Bulk RNA-seq from human XDP and isogenic SVA-deleted striatal organoids used to resolve repeat-RNA, R-loop, and neuronal-injury mechanisms.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[41],"sample_count":41,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40540399"],"publication_contexts":[{"context_id":"disorder:X-linked_Dystonia-Parkinsonism","publication":"PMID:40540399"}],"publication":"PMID:40540399","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40540399","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified and metadata-verified with scripts/discover_datasets.py on 2026-08-11."],"contexts":[{"id":"disorder:X-linked_Dystonia-Parkinsonism","name":"X-linked Dystonia-Parkinsonism","kind":"Disorder","source_path":"kb/disorders/X-linked_Dystonia-Parkinsonism.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/X-linked_Dystonia-Parkinsonism.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/X-linked_Dystonia-Parkinsonism.html#dataset-geo-gse289534"}],"context_names":["X-linked Dystonia-Parkinsonism"],"disease_names":["X-linked Dystonia-Parkinsonism"],"disease_name":"X-linked Dystonia-Parkinsonism","same_context_model_ids":["model:kb/disorders/X-linked_Dystonia-Parkinsonism.yaml:Human neural-progenitor SVA mini-heterochromatin model","model:kb/disorders/X-linked_Dystonia-Parkinsonism.yaml:Isogenic XDP striatal organoid repeat-RNA model","model:kb/disorders/X-linked_Dystonia-Parkinsonism.yaml:Patient-derived fibroblast and neural-progenitor G-quadruplex model","model:kb/disorders/X-linked_Dystonia-Parkinsonism.yaml:XDP iPSC-derived neural stem cells and medium spiny neurons","model:kb/disorders/X-linked_Dystonia-Parkinsonism.yaml:XDP iPSC-derived neuronal lineages with CRISPR SVA excision"],"candidate_model_ids":["model:kb/disorders/X-linked_Dystonia-Parkinsonism.yaml:Isogenic XDP striatal organoid repeat-RNA model"],"association_basis":"Same publication as a NAM (candidate)","nam_disease_context":"Same publication as a NAM (candidate)","source_paths":["kb/disorders/X-linked_Dystonia-Parkinsonism.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/X-linked_Dystonia-Parkinsonism.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/X-linked_Dystonia-Parkinsonism.html#dataset-geo-gse289534"]},{"id":"dataset:geo:gse289575","accession":"geo:GSE289575","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE289575","title":"Multi-omics Analysis of Skeletal Muscle Identifies Dysregulation of Hypoxia-Induced Genes in Peripheral Artery Disease [RRBS]","alternate_titles":[],"description":"Epigenetic modifications such as DNA methylation play a critical role in hypoxic cell programs. However, no previous studies have investigated the epigenetic regulation of gene expression in peripheral artery disease (PAD), a condition characterized by intermittent ischemia. In this study, we used reduced representation bisulphite sequencing (RRBS) to investigate how PAD affects the DNA methylome in skeletal muscle of PAD patients with intermittent claudication (IC) or critical limb ischemia (CLI) compared to non-PAD controls. We also used small and bulk RNA-sequencing (RNA-seq), which allowed for data integration.","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[40],"sample_count":40,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41025488"],"publication_contexts":[{"context_id":"disorder:Peripheral_Artery_Disease","publication":"PMID:41025488"}],"publication":"PMID:41025488","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41025488","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Peripheral Artery Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Peripheral_Artery_Disease","name":"Peripheral Artery Disease","kind":"Disorder","source_path":"kb/disorders/Peripheral_Artery_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Peripheral_Artery_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Peripheral_Artery_Disease.html#dataset-geo-gse289575"}],"context_names":["Peripheral Artery Disease"],"disease_names":["Peripheral Artery Disease"],"disease_name":"Peripheral Artery Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Peripheral_Artery_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Peripheral_Artery_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Peripheral_Artery_Disease.html#dataset-geo-gse289575"]},{"id":"dataset:geo:gse289753","accession":"geo:GSE289753","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE289753","title":"A Novel Combination Therapy with Uridine and Praziquantel effectively Alleviates Schistosomiasis-induced Hepatic Fibrosis through Promoting Adipogenic Differentiation","alternate_titles":[],"description":"Schistosomiasis-induced hepatic fibrosis, a consequence of egg-induced granulomatous lesions, remains untreated by current drugs. Therefore, the development of novel antifibrosis drugs is of paramount importance. Our previous study indicated that aberrant uridine concentrations play a pivotal role in schistosomiasis-induced hepatic fibrosis. This study aimed to explore the inhibitory role of uridine in schistosomiasis-induced liver fibrosis and the regulatory mechanism of uridine on hepatic stellate cell (HSC) activation. The results indicated that uridine could inhibit schistosomiasis-induced liver fibrosis in vivo and TGF-β-induced HSC activation in vitro.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[9],"sample_count":9,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Schistosomiasis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Schistosomiasis","name":"Schistosomiasis","kind":"Disorder","source_path":"kb/disorders/Schistosomiasis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Schistosomiasis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Schistosomiasis.html#dataset-geo-gse289753"}],"context_names":["Schistosomiasis"],"disease_names":["Schistosomiasis"],"disease_name":"Schistosomiasis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Schistosomiasis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Schistosomiasis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Schistosomiasis.html#dataset-geo-gse289753"]},{"id":"dataset:geo:gse289809","accession":"geo:GSE289809","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE289809","title":"Exploration of common pathogenic genes between cerebral amyloid angiopathy and insomnia based on bioinformatics and experimental validation","alternate_titles":[],"description":"RNA transcriptome analysis results were utilized to assess the shared gene expression between patients with cerebral amyloid angiopathy (CAA) and those with insomnia.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[22],"sample_count":22,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40685483"],"publication_contexts":[{"context_id":"disorder:Cerebral_Amyloid_Angiopathy","publication":"PMID:40685483"}],"publication":"PMID:40685483","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40685483","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Cerebral Amyloid Angiopathy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Cerebral_Amyloid_Angiopathy","name":"Cerebral Amyloid Angiopathy","kind":"Disorder","source_path":"kb/disorders/Cerebral_Amyloid_Angiopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cerebral_Amyloid_Angiopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cerebral_Amyloid_Angiopathy.html#dataset-geo-gse289809"}],"context_names":["Cerebral Amyloid Angiopathy"],"disease_names":["Cerebral Amyloid Angiopathy"],"disease_name":"Cerebral Amyloid Angiopathy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cerebral_Amyloid_Angiopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cerebral_Amyloid_Angiopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cerebral_Amyloid_Angiopathy.html#dataset-geo-gse289809"]},{"id":"dataset:geo:gse289957","accession":"geo:GSE289957","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE289957","title":"Differential Gene Expression related to Telomere Length in Arterial Wall Tissues and Granulocytes of Patients with Coronary Artery Disease","alternate_titles":[],"description":"Shortened telomere length (TL) in blood cells is associated with atherosclerotic coronary artery disease (CAD). However, the mechanistic pathways underlying TL attrition in arterial wall tissues for patients with CAD remain unclear. In this study, we evaluated TL in arterial wall tissues and granulocytes and correlated these measurements with data on gene expressions in the arterial wall tissues of patients with CAD.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[34],"sample_count":34,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42211145"],"publication_contexts":[{"context_id":"disorder:Coronary_Artery_Disease","publication":"PMID:42211145"}],"publication":"PMID:42211145","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42211145","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Coronary Artery Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Coronary_Artery_Disease","name":"Coronary Artery Disease","kind":"Disorder","source_path":"kb/disorders/Coronary_Artery_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Coronary_Artery_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Coronary_Artery_Disease.html#dataset-geo-gse289957"}],"context_names":["Coronary Artery Disease"],"disease_names":["Coronary Artery Disease"],"disease_name":"Coronary Artery Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Coronary_Artery_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Coronary_Artery_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Coronary_Artery_Disease.html#dataset-geo-gse289957"]},{"id":"dataset:geo:gse289984","accession":"geo:GSE289984","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE289984","title":"Next-generation sequencing profiling of miRNAs in individuals with 22q11.2 deletion syndrome revealed altered expression of miR-185-5p","alternate_titles":[],"description":"Background: The 22q11.2 deletion syndrome (22q11.2DS) is a microdeletion syndrome with highly variable phenotypic manifestations, even though most patients present the typical 3 Mb microdeletion, usually affecting the same ~ 106 genes. One of the genes affected by this deletion is DGCR8, which plays a crucial role in miRNA biogenesis. Therefore, the haploinsufficiency of DGCR8 due to this microdeletion can alter the modulation of the expression of several miRNAs involved in a range of biological processes.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[24],"sample_count":24,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:38872198"],"publication_contexts":[{"context_id":"disorder:22q11.2_Deletion_Syndrome","publication":"PMID:38872198"}],"publication":"PMID:38872198","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/38872198","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for 22q11.2 Deletion Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:22q11.2_Deletion_Syndrome","name":"22q11.2 Deletion Syndrome","kind":"Disorder","source_path":"kb/disorders/22q11.2_Deletion_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/22q11.2_Deletion_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/22q11.2_Deletion_Syndrome.html#dataset-geo-gse289984"}],"context_names":["22q11.2 Deletion Syndrome"],"disease_names":["22q11.2 Deletion Syndrome"],"disease_name":"22q11.2 Deletion Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/22q11.2_Deletion_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/22q11.2_Deletion_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/22q11.2_Deletion_Syndrome.html#dataset-geo-gse289984"]},{"id":"dataset:geo:gse290027","accession":"geo:GSE290027","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE290027","title":"IL-32 producing CD8+ memory T cells and Tregs define the IDO1 / PD-L1 niche in human cutaneous leishmaniasis skin lesions","alternate_titles":[],"description":"Human cutaneous leishmaniasis (CL) is characterised by chronic skin pathology. Experimental and clinical data suggest that immune checkpoints (ICs) play a crucial role in disease outcome but the cellular and molecular niches that facilitate IC expression during leishmaniasis are ill-defined. We previously showed that in Sri Lankan patients with CL, indoleamine 2,3-dioxygenase 1 (IDO1) and programmed death-ligand 1 (PD-L1) are enriched in lesion skin and that reduced PD-L1 expression early after treatment onset predicted cure rate following antimonial therapy.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40371647"],"publication_contexts":[{"context_id":"disorder:Leishmaniasis","publication":"PMID:40371647"}],"publication":"PMID:40371647","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40371647","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Leishmaniasis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Leishmaniasis","name":"Leishmaniasis","kind":"Disorder","source_path":"kb/disorders/Leishmaniasis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Leishmaniasis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Leishmaniasis.html#dataset-geo-gse290027"}],"context_names":["Leishmaniasis"],"disease_names":["Leishmaniasis"],"disease_name":"Leishmaniasis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Leishmaniasis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Leishmaniasis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Leishmaniasis.html#dataset-geo-gse290027"]},{"id":"dataset:geo:gse290099","accession":"geo:GSE290099","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE290099","title":"Immune response of human lung tissue after infection with human parainfluenza virus-3 – canonical pathways and treatment","alternate_titles":[],"description":"Ex vivo human precision-cut lung slices (PCLS) were infected with human parainfluenza virus 3 (hPIV-3). We used microarry to explore the changes in gene expression between infected and non-infected, same-donor PCLS. We particularly analyzed changes in mRNA and miRNA expression levels linked to inflammation and antiviral immunity.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[31],"sample_count":31,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41239423"],"publication_contexts":[{"context_id":"disorder:Parainfluenza_Virus_Infection","publication":"PMID:41239423"}],"publication":"PMID:41239423","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41239423","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Parainfluenza Virus Infection (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Parainfluenza_Virus_Infection","name":"Parainfluenza Virus Infection","kind":"Disorder","source_path":"kb/disorders/Parainfluenza_Virus_Infection.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Parainfluenza_Virus_Infection.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Parainfluenza_Virus_Infection.html#dataset-geo-gse290099"}],"context_names":["Parainfluenza Virus Infection"],"disease_names":["Parainfluenza Virus Infection"],"disease_name":"Parainfluenza Virus Infection","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Parainfluenza_Virus_Infection.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Parainfluenza_Virus_Infection.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Parainfluenza_Virus_Infection.html#dataset-geo-gse290099"]},{"id":"dataset:geo:gse290213","accession":"geo:GSE290213","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE290213","title":"A single cell transcriptional profile of benign prostatic hyperplasia","alternate_titles":[],"description":"Benign prostatic hyperplasia (BPH) is characterized by excessive cell proliferation and inflammation and affects most aging men. The development of new therapies for BPH requires a deeper understanding of the underlying pathophysiology and cellular components of BPH. Single-cell RNA-sequencing was performed on prostate tissue from 15 patients undergoing holmium laser enucleation of the prostate for treatment of BPH. Clustering and differential expression analysis on aligned single cell RNA-seq data was performed to annotate all cell types. 16,234 cells were analyzed and specific stromal, epithelial, and immune subgroups were found to be strongly associated with inflammation.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[27],"sample_count":27,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41832222"],"publication_contexts":[{"context_id":"disorder:Benign_Prostatic_Hyperplasia","publication":"PMID:41832222"}],"publication":"PMID:41832222","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41832222","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Benign Prostatic Hyperplasia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Benign_Prostatic_Hyperplasia","name":"Benign Prostatic Hyperplasia","kind":"Disorder","source_path":"kb/disorders/Benign_Prostatic_Hyperplasia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Benign_Prostatic_Hyperplasia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Benign_Prostatic_Hyperplasia.html#dataset-geo-gse290213"}],"context_names":["Benign Prostatic Hyperplasia"],"disease_names":["Benign Prostatic Hyperplasia"],"disease_name":"Benign Prostatic Hyperplasia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Benign_Prostatic_Hyperplasia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Benign_Prostatic_Hyperplasia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Benign_Prostatic_Hyperplasia.html#dataset-geo-gse290213"]},{"id":"dataset:geo:gse290354","accession":"geo:GSE290354","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE290354","title":"Characterization of a novel zebrafish model of MTMR5-associated Charcot-Marie-Tooth disease type 4B3","alternate_titles":[],"description":"Brain-enriched bulk RNA sequencing from the mtmr5 full-gene-deletion zebrafish line curated under animal_models, n=8. This is the transcriptomic dataset behind the neurogenesis, chromatin-remodelling and synaptic-membrane-homeostasis pathways reported for that model. Zebrafish brain, so it speaks to the CNS arm of the disease rather than to the peripheral nerve lesion.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:7955","label":"Danio rerio","display_label":"zebrafish","url":"http://purl.obolibrary.org/obo/NCBITaxon_7955"}],"organism_labels":["Danio rerio"],"organism_label":"Danio rerio","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40066109"],"publication_contexts":[{"context_id":"disorder:Charcot-Marie-Tooth_Disease_Type_4B3","publication":"PMID:40066109"}],"publication":"PMID:40066109","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40066109","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE290354","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE290354","reference_title":"Characterization of a novel zebrafish model of MTMR5-associated Charcot-Marie-Tooth disease type 4B3","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"RNA sequencing from brain-enriched samples identifies novel disease pathways including transcriptional changes in genes responsible for neurogenesis, chromatin remodeling/organization, and synaptic membrane homeostasis.","explanation":"The GEO record's own summary of what this dataset measured and found."}],"notes":["The only DIRECT dataset candidate found for CMT4B3. A second candidate, geo:GSE190699, was surfaced by gene-only matching on SBF1 and rejected on triage: it is a multiple myeloma study with no relationship to this disease."],"contexts":[{"id":"disorder:Charcot-Marie-Tooth_Disease_Type_4B3","name":"Charcot-Marie-Tooth Disease Type 4B3","kind":"Disorder","source_path":"kb/disorders/Charcot-Marie-Tooth_Disease_Type_4B3.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Charcot-Marie-Tooth_Disease_Type_4B3.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Charcot-Marie-Tooth_Disease_Type_4B3.html#dataset-geo-gse290354"}],"context_names":["Charcot-Marie-Tooth Disease Type 4B3"],"disease_names":["Charcot-Marie-Tooth Disease Type 4B3"],"disease_name":"Charcot-Marie-Tooth Disease Type 4B3","same_context_model_ids":["model:kb/disorders/Charcot-Marie-Tooth_Disease_Type_4B3.yaml:CMT4B3 patient dermal fibroblasts (R763H/G1064E)","model:kb/disorders/Charcot-Marie-Tooth_Disease_Type_4B3.yaml:CMT4B3 patient-derived iPSC lines"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Charcot-Marie-Tooth_Disease_Type_4B3.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Charcot-Marie-Tooth_Disease_Type_4B3.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Charcot-Marie-Tooth_Disease_Type_4B3.html#dataset-geo-gse290354"]},{"id":"dataset:geo:gse290549","accession":"geo:GSE290549","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE290549","title":"Common Connective Tissue Disorder and Anti-Cytokine Autoantibodies are Enriched in Idiopathic Multicentric Castleman Disease Patients [CTD Array version 3]","alternate_titles":[],"description":"We measued IgG autoantibodies associated with Connective Tissue Diseases (CTDs) and Anti-Cytokine Antibodies (ACA) in idiopathic Multicentric Castleman Disease (iMCD) patients and healthy controls who received the BNT162b2 vaccine.","alternate_descriptions":[],"data_types":["PROTEOMICS"],"data_type_labels":["Protein expression profiling"],"data_type_label":"Protein expression profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[151],"sample_count":151,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40181993"],"publication_contexts":[{"context_id":"disorder:Idiopathic_Multicentric_Castleman_Disease","publication":"PMID:40181993"}],"publication":"PMID:40181993","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40181993","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Castleman Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values. This is the autoantibody array underlying the autoimmune_etiology hypothesis group."],"contexts":[{"id":"disorder:Idiopathic_Multicentric_Castleman_Disease","name":"Idiopathic Multicentric Castleman Disease","kind":"Disorder","source_path":"kb/disorders/Idiopathic_Multicentric_Castleman_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Idiopathic_Multicentric_Castleman_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Idiopathic_Multicentric_Castleman_Disease.html#dataset-geo-gse290549"}],"context_names":["Idiopathic Multicentric Castleman Disease"],"disease_names":["Idiopathic Multicentric Castleman Disease"],"disease_name":"Idiopathic Multicentric Castleman Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Idiopathic_Multicentric_Castleman_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Idiopathic_Multicentric_Castleman_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Idiopathic_Multicentric_Castleman_Disease.html#dataset-geo-gse290549"]},{"id":"dataset:geo:gse290798","accession":"geo:GSE290798","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE290798","title":"Multi-omics analysis unveiled fibroblast-mediated pathogenesis in male genital lichen sclerosus","alternate_titles":[],"description":"Male genital lichen sclerosus (MGLSc), a chronic inflammatory dermatological condition, has been recognized for its profound implications on the quality of life among males. The exact etiological factors behind this prevalent condition remained largely enigmatic. In this research, we employed a multi-omics strategy to identify and elucidate the underlying histological biomarkers and the fundamental pathogenesis associated with MGLSc. Generally, a comprehensive cell atlas of MGLSc disease was constructed, highlighting a pronounced increase in T cells coupled with a remarkable reduction in keratinocytes within the MGLSc samples.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[9],"sample_count":9,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40745572"],"publication_contexts":[{"context_id":"disorder:Genital_Lichen_Sclerosus","publication":"PMID:40745572"}],"publication":"PMID:40745572","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40745572","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Genital Lichen Sclerosus (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Genital_Lichen_Sclerosus","name":"Genital Lichen Sclerosus","kind":"Disorder","source_path":"kb/disorders/Genital_Lichen_Sclerosus.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Genital_Lichen_Sclerosus.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Genital_Lichen_Sclerosus.html#dataset-geo-gse290798"}],"context_names":["Genital Lichen Sclerosus"],"disease_names":["Genital Lichen Sclerosus"],"disease_name":"Genital Lichen Sclerosus","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Genital_Lichen_Sclerosus.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Genital_Lichen_Sclerosus.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Genital_Lichen_Sclerosus.html#dataset-geo-gse290798"]},{"id":"dataset:geo:gse290850","accession":"geo:GSE290850","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE290850","title":"Dupilumab inhibits proliferation of malignant lymphocytes in Sezary syndrome and boosts anti-tumor immunity","alternate_titles":[],"description":"Patients with Sezary syndrome (SS), the aggressive leukemic variant of cutaneous T-cell lymphoma, have few therapeutic options and a poor prognosis. We previously showed that the IL4/IL13 signaling pathway is critical in SS tumorigenesis. Here we investigated the potential therapeutic effect of inhibiting IL4/IL13 signaling with REGN668 (Dupilumab), a monoclonal antibody that blocks the IL4/IL13 pathway by targeting IL4Rα, the common subunit of the IL4 and IL13 receptors.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[11],"sample_count":11,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41159943"],"publication_contexts":[{"context_id":"disorder:Sezary_Syndrome","publication":"PMID:41159943"}],"publication":"PMID:41159943","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41159943","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Sezary Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Sezary_Syndrome","name":"Sezary Syndrome","kind":"Disorder","source_path":"kb/disorders/Sezary_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sezary_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Sezary_Syndrome.html#dataset-geo-gse290850"}],"context_names":["Sezary Syndrome"],"disease_names":["Sezary Syndrome"],"disease_name":"Sezary Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Sezary_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sezary_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Sezary_Syndrome.html#dataset-geo-gse290850"]},{"id":"dataset:geo:gse291004","accession":"geo:GSE291004","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE291004","title":"Keratinocyte-secreted SAA1 induces a population of long-lived antigen-presenting neutrophils that drives Sweet Syndrome","alternate_titles":[],"description":"Sweet syndrome (also known as acute febrile neutrophilic dermatosis), is a rare inflammatory skin disorder characterized by erythematous plaques with a dense dermal neutrophilic infiltrate. It remains unknown how neutrophils, which are generally short-lived, persist in the skin of patients with Sweet syndrome. We report that Sweet syndrome skin contains a unique population of long-lived antigen-presenting cell (APC)-neutrophils that are not present in blood or unaffected skin.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[17],"sample_count":17,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Sweet Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Sweet_Syndrome","name":"Sweet Syndrome","kind":"Disorder","source_path":"kb/disorders/Sweet_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sweet_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Sweet_Syndrome.html#dataset-geo-gse291004"}],"context_names":["Sweet Syndrome"],"disease_names":["Sweet Syndrome"],"disease_name":"Sweet Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Sweet_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sweet_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Sweet_Syndrome.html#dataset-geo-gse291004"]},{"id":"dataset:geo:gse291177","accession":"geo:GSE291177","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE291177","title":"RNAseq of Mineralocorticoid Receptor (MR) overexpression in UVB-induced ocular rosacea model on meibomian glands of rats","alternate_titles":[],"description":"Rat meibomian-gland bulk RNA-seq from the UVB-induced ocular rosacea model, comparing wild-type animals with rats overexpressing the human mineralocorticoid receptor. Companion to GSE277020 from the same model and aligned to the meibomian gland dysfunction node.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10116","label":"Rattus norvegicus","display_label":"Rattus norvegicus","url":"http://purl.obolibrary.org/obo/NCBITaxon_10116"}],"organism_labels":["Rattus norvegicus"],"organism_label":"Rattus norvegicus","sample_types":[],"sample_type_labels":[],"sample_counts":[17],"sample_count":17,"conditions":["UVB-irradiated wild-type rat meibomian glands","UVB-irradiated mineralocorticoid-receptor-overexpressing rat meibomian glands","non-irradiated wild-type and transgenic controls"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE291177","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE291177","reference_title":"RNAseq of Mineralocorticoid Receptor (MR) overexpression in UVB-induced ocular rosacea model on meibomian glands of rats","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"The aim of this study was to analyse the transcriptional regulation of UVB-induced ocular rosacea model on the meibomian glands of rats that overexpress the human NRC32 gene coding for mineralocorticoid receptor (P1.hMR) and age- and sex- matched wild type (WT) littlemates.","explanation":"GEO summary identifies this as a meibomian-gland transcriptome from the UVB ocular rosacea model, matching the ocular subgraph."}],"notes":["No linked publication is listed on the GEO record at time of curation."],"contexts":[{"id":"disorder:Rosacea","name":"Rosacea","kind":"Disorder","source_path":"kb/disorders/Rosacea.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rosacea.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Rosacea.html#dataset-geo-gse291177"}],"context_names":["Rosacea"],"disease_names":["Rosacea"],"disease_name":"Rosacea","same_context_model_ids":["model:kb/disorders/Rosacea.yaml:HaCaT keratinocytes under simulated rosacea conditions","model:kb/disorders/Rosacea.yaml:Paired lesional and non-lesional papulopustular rosacea skin explants","model:kb/disorders/Rosacea.yaml:SZ95 sebocyte and live Demodex mite co-culture"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Rosacea.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rosacea.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Rosacea.html#dataset-geo-gse291177"]},{"id":"dataset:geo:gse291197","accession":"geo:GSE291197","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE291197","title":"ATRX loss couples genome instability at a G-rich repeat to dysregulation of human alpha-globin expression [ChIP-seq]","alternate_titles":[],"description":"Germline mutations in the chromatin remodelling protein ATRX cause a severe developmental disorder associated with α-thalassemia. In addition, ATRX is amongst the twenty genes most frequently mutated in cancer. How ATRX mutations alter gene expression remains unclear. Using the α-globin locus as a model, here we show that ATRX deficiency downregulates α-globin in a subset of cells exhibiting DNA damage. A G-rich repeat at the α-globin locus serves as a potential site of G-quadruplex formation and DNA damage. ATRX binds this repeat co-transcriptionally, and its loss increases R-loop accumulation at this site, leading to local DNA damage and transcriptional disruption in cis.","alternate_descriptions":[],"data_types":["CHIP_SEQ"],"data_type_labels":["Chromatin immunoprecipitation sequencing"],"data_type_label":"Chromatin immunoprecipitation sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[10],"sample_count":10,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41688464"],"publication_contexts":[{"context_id":"disorder:Alpha_Thalassemia","publication":"PMID:41688464"}],"publication":"PMID:41688464","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41688464","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Alpha Thalassemia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Alpha_Thalassemia","name":"Alpha Thalassemia","kind":"Disorder","source_path":"kb/disorders/Alpha_Thalassemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alpha_Thalassemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Alpha_Thalassemia.html#dataset-geo-gse291197"}],"context_names":["Alpha Thalassemia"],"disease_names":["Alpha Thalassemia"],"disease_name":"Alpha Thalassemia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Alpha_Thalassemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alpha_Thalassemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Alpha_Thalassemia.html#dataset-geo-gse291197"]},{"id":"dataset:geo:gse291247","accession":"geo:GSE291247","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE291247","title":"DLEU2 promotes cell motility and immune infiltration in cervical squamous cell carcinoma through reciprocal feed-forward activation of E2F1","alternate_titles":[],"description":"Cancer metastasis is the primary cause of high mortality in patients with cervical squamous cell carcinoma (CESC). The invasive ability of cancer cells is enhanced by increased cell motility, which contributes to their distant metastasis. The oncogenic lncRNA DLEU2, implicated in tumor progression and prognosis, remains understudied in CESC. This study investigated how DLEU2 enhances cell motility and regulates immune infiltration in CESC. We found that DLEU2 was upregulated in CESC tissues and correlated with poor prognosis in advanced-stage patients. Functionally, DLEU2 knockdown suppressed cell migration and invasion, while its overexpression enhanced motility.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[16],"sample_count":16,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42091655"],"publication_contexts":[{"context_id":"disorder:Cervical_Squamous_Cell_Carcinoma","publication":"PMID:42091655"}],"publication":"PMID:42091655","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42091655","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Cervical Squamous Cell Carcinoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Cervical_Squamous_Cell_Carcinoma","name":"Cervical Squamous Cell Carcinoma","kind":"Disorder","source_path":"kb/disorders/Cervical_Squamous_Cell_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cervical_Squamous_Cell_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cervical_Squamous_Cell_Carcinoma.html#dataset-geo-gse291247"}],"context_names":["Cervical Squamous Cell Carcinoma"],"disease_names":["Cervical Squamous Cell Carcinoma"],"disease_name":"Cervical Squamous Cell Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cervical_Squamous_Cell_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cervical_Squamous_Cell_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cervical_Squamous_Cell_Carcinoma.html#dataset-geo-gse291247"]},{"id":"dataset:geo:gse291267","accession":"geo:GSE291267","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE291267","title":"DUX4.6 siRNA in vitro activity in FSHD patient-derived myotubes","alternate_titles":[],"description":"Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant muscular disease caused by the aberrant ectopic expression of DUX4 in skeletal muscle. There are no approved therapies for FSHD to date, and strategies aimed at reducing DUX4 expression in skeletal muscle of FSHD patients are promising therapeutic approaches. Here we demonstrate DUX4.6 siRNA activity in reducing DUX4-regulated gene expression in FSHD patient-derived myotubes in vitro.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[32],"sample_count":32,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41994867"],"publication_contexts":[{"context_id":"disorder:Facioscapulohumeral_Muscular_Dystrophy","publication":"PMID:41994867"}],"publication":"PMID:41994867","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41994867","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Facioscapulohumeral Muscular Dystrophy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Facioscapulohumeral_Muscular_Dystrophy","name":"Facioscapulohumeral Muscular Dystrophy","kind":"Disorder","source_path":"kb/disorders/Facioscapulohumeral_Muscular_Dystrophy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Facioscapulohumeral_Muscular_Dystrophy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Facioscapulohumeral_Muscular_Dystrophy.html#dataset-geo-gse291267"}],"context_names":["Facioscapulohumeral Muscular Dystrophy"],"disease_names":["Facioscapulohumeral Muscular Dystrophy"],"disease_name":"Facioscapulohumeral Muscular Dystrophy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Facioscapulohumeral_Muscular_Dystrophy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Facioscapulohumeral_Muscular_Dystrophy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Facioscapulohumeral_Muscular_Dystrophy.html#dataset-geo-gse291267"]},{"id":"dataset:geo:gse291694","accession":"geo:GSE291694","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE291694","title":"Stem cell-derived human glutamatergic neurons with pathogenic KCNQ2 variants display hyperactive bursting phenotypes","alternate_titles":[],"description":"Transcriptional profiling of glutamatergic neurons differentiated from patient-derived iPSCs carrying three distinct KCNQ2 pathogenic variants (L292_L293delinsPF, G256W, T274M) alongside CRISPR-Cas9-corrected isogenic controls for each. Because every variant line has its own isogenic control, the series separates variant effect from donor background - and the accompanying high-density microelectrode-array work supplies the functional counterpart (increased burst duration in all three lines, retigabine rescue of the G256W network).","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[42],"sample_count":42,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:6296","label":"KCNQ2","display_label":"KCNQ2","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/6296"}],"genes":["KCNQ2"],"platforms":[],"platform":null,"publications":["PMID:41015095"],"publication_contexts":[{"context_id":"disorder:KCNQ2_Developmental_and_Epileptic_Encephalopathy","publication":"PMID:41015095"}],"publication":"PMID:41015095","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41015095","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Found by a targeted GEO DataSets title search for KCNQ2; accession verified against NCBI E-utilities on 2026-08-27. Sample count is GEO's own value. Organism is recorded here as human on the strength of the series summary and the sample titles, which are the patient and isogenic iPSC line names - GEO's own sample_organism/platform fields say Mus musculus (GPL24247), which appears to be a submission metadata error rather than a description of the material."],"contexts":[{"id":"disorder:KCNQ2_Developmental_and_Epileptic_Encephalopathy","name":"KCNQ2 Developmental and Epileptic Encephalopathy","kind":"Disorder","source_path":"kb/disorders/KCNQ2_Developmental_and_Epileptic_Encephalopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/KCNQ2_Developmental_and_Epileptic_Encephalopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/KCNQ2_Developmental_and_Epileptic_Encephalopathy.html#dataset-geo-gse291694"}],"context_names":["KCNQ2 Developmental and Epileptic Encephalopathy"],"disease_names":["KCNQ2 Developmental and Epileptic Encephalopathy"],"disease_name":"KCNQ2 Developmental and Epileptic Encephalopathy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/KCNQ2_Developmental_and_Epileptic_Encephalopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/KCNQ2_Developmental_and_Epileptic_Encephalopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/KCNQ2_Developmental_and_Epileptic_Encephalopathy.html#dataset-geo-gse291694"]},{"id":"dataset:geo:gse291847","accession":"geo:GSE291847","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE291847","title":"Targeting GLP-1 signaling ameliorates cystogenesis in a zebrafish model of nephronophthisis","alternate_titles":[],"description":"Nephronophthisis (NPH) is the leading genetic cause of end-stage renal disease in children and young adults, with no effective disease-modifying therapies currently available. Here, we identify glucagon-like peptide-1 (GLP-1) signaling as a novel therapeutic target for NPH through a systematic drug repurposing screen in zebrafish. By simultaneously depleting nphp1 and nphp4, we developed a robust zebrafish model that recapitulates key features of human NPH, including glomerular cyst formation. Our screen revealed that dipeptidyl peptidase-4 (DPP4) inhibitors (Omarigliptin and Linagliptin) and GLP-1 receptor agonists (Semaglutide) significantly reduce cystogenesis in a dose-dependent manner.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:7955","label":"Danio rerio","display_label":"zebrafish","url":"http://purl.obolibrary.org/obo/NCBITaxon_7955"}],"organism_labels":["Danio rerio"],"organism_label":"Danio rerio","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40806500"],"publication_contexts":[{"context_id":"disorder:Nephronophthisis","publication":"PMID:40806500"}],"publication":"PMID:40806500","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40806500","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Nephronophthisis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Nephronophthisis","name":"Nephronophthisis","kind":"Disorder","source_path":"kb/disorders/Nephronophthisis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Nephronophthisis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Nephronophthisis.html#dataset-geo-gse291847"}],"context_names":["Nephronophthisis"],"disease_names":["Nephronophthisis"],"disease_name":"Nephronophthisis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Nephronophthisis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Nephronophthisis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Nephronophthisis.html#dataset-geo-gse291847"]},{"id":"dataset:geo:gse291954","accession":"geo:GSE291954","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE291954","title":"Inflammatory transcriptomic signatures in a human cellular NMOSD model reveal upregulation of NF-κB and IL6 pathways","alternate_titles":[],"description":"Neuromyelitis optica spectrum disorder (NMOSD) is a rare neurological autoimmune disease caused autoantibodies targeting the astrocytic water channel aquaporin-4 (AQP4). Binding to AQP4 initiates the activation of innate immune components, especially the complement system. Both in-vivo and in-vitro models have been developed to study the molecular pathophysiology of NMOSD. The aim of our study was to characterize the molecular response of four human cell lines (AQP4-ECFP expressing U-87MG glioblastoma cells, U-87MG expressing only ECFP, HEK293 cells expressing AQP4-EmGFP and human primary astrocytes) to a treatment with AQP4 antibody E5415A and human complement.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[60],"sample_count":60,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41361218"],"publication_contexts":[{"context_id":"disorder:Neuromyelitis_Optica","publication":"PMID:41361218"},{"context_id":"disorder:Neuromyelitis_Optica_Spectrum_Disorder","publication":"PMID:41361218"}],"publication":"PMID:41361218","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41361218","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Neuromyelitis Optica (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.","Identified by GEO DataSets index search for Neuromyelitis Optica Spectrum Disorder (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Neuromyelitis_Optica","name":"Neuromyelitis Optica","kind":"Disorder","source_path":"kb/disorders/Neuromyelitis_Optica.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Neuromyelitis_Optica.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Neuromyelitis_Optica.html#dataset-geo-gse291954"},{"id":"disorder:Neuromyelitis_Optica_Spectrum_Disorder","name":"Neuromyelitis Optica Spectrum Disorder","kind":"Disorder","source_path":"kb/disorders/Neuromyelitis_Optica_Spectrum_Disorder.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Neuromyelitis_Optica_Spectrum_Disorder.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Neuromyelitis_Optica_Spectrum_Disorder.html#dataset-geo-gse291954"}],"context_names":["Neuromyelitis Optica","Neuromyelitis Optica Spectrum Disorder"],"disease_names":["Neuromyelitis Optica","Neuromyelitis Optica Spectrum Disorder"],"disease_name":"Neuromyelitis Optica","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Neuromyelitis_Optica.yaml","kb/disorders/Neuromyelitis_Optica_Spectrum_Disorder.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Neuromyelitis_Optica.yaml","https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Neuromyelitis_Optica_Spectrum_Disorder.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Neuromyelitis_Optica.html#dataset-geo-gse291954","https://dismech.monarchinitiative.org/pages/disorders/Neuromyelitis_Optica_Spectrum_Disorder.html#dataset-geo-gse291954"]},{"id":"dataset:geo:gse291962","accession":"geo:GSE291962","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE291962","title":"CCR8 expression on regulatory T cells reveals trajectories of tissue adaptation and protects against myocardial infarction [bulk RNA-seq]","alternate_titles":[],"description":"We employed single-cell RNA sequencing (scRNA-seq) in a mouse model of MI to gain a detailed analysis of heart and lymphoid Tregs, focusing on their developmental trajectories. Bulk RNA sequencing was used to further characterize the phenotype of CC motif chemokine receptor 8 positive (CCR8+) Tregs in the heart and lymph nodes. scRNA-seq of murine Tregs from the mediastinal lymph node (mLN) and heart after MI identified three Treg populations, one of which was mainly derived from the heart.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[16],"sample_count":16,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41685444"],"publication_contexts":[{"context_id":"disorder:Myocardial_Infarction","publication":"PMID:41685444"}],"publication":"PMID:41685444","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41685444","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Myocardial Infarction (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Myocardial_Infarction","name":"Myocardial Infarction","kind":"Disorder","source_path":"kb/disorders/Myocardial_Infarction.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myocardial_Infarction.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Myocardial_Infarction.html#dataset-geo-gse291962"}],"context_names":["Myocardial Infarction"],"disease_names":["Myocardial Infarction"],"disease_name":"Myocardial Infarction","same_context_model_ids":["model:kb/disorders/Myocardial_Infarction.yaml:Bioelectronically instrumented heart-on-a-chip under acute hypoxia","model:kb/disorders/Myocardial_Infarction.yaml:Epicardial-myocardial heart-on-a-chip model of ischemia-reperfusion injury","model:kb/disorders/Myocardial_Infarction.yaml:Human cardiac infarct organoid with an internal oxygen-diffusion gradient","model:kb/disorders/Myocardial_Infarction.yaml:Human heart-on-a-chip ischemia-reperfusion assay with endothelial extracellular vesicle rescue","model:kb/disorders/Myocardial_Infarction.yaml:Myocardial infarct border-zone-on-a-chip"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Myocardial_Infarction.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myocardial_Infarction.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Myocardial_Infarction.html#dataset-geo-gse291962"]},{"id":"dataset:geo:gse292071","accession":"geo:GSE292071","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE292071","title":"A Single-cell Atlas of Schwannoma Across Genetic Backgrounds and Anatomic Locations","alternate_titles":[],"description":"Background: Schwannomas are nerve sheath tumors arising at cranial and peripheral nerves, either sporadically or in patients with a schwannomatosis-predisposition syndrome. There is limited understanding of the transcriptional heterogeneity of schwannomas across genetic backgrounds and anatomic locations. Methods: Here, we prospectively profile by single-cell full-length transcriptomics tumors from 22 patients with NF2-related schwannomatosis, non-NF2-related schwannomatosis, and sporadic schwannomas, resected from cranial and peripheral nerves. We profiled 11,373 cells, including neoplastic cells, fibroblasts, T cells, endothelial cells, myeloid cells and pericytes.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[151],"sample_count":151,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40217315"],"publication_contexts":[{"context_id":"disorder:Schwannoma","publication":"PMID:40217315"},{"context_id":"disorder:Schwannomatosis","publication":"PMID:40217315"}],"publication":"PMID:40217315","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40217315","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Schwannoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.","Identified by GEO DataSets index search for Schwannomatosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Schwannoma","name":"Schwannoma","kind":"Disorder","source_path":"kb/disorders/Schwannoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Schwannoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Schwannoma.html#dataset-geo-gse292071"},{"id":"disorder:Schwannomatosis","name":"Schwannomatosis","kind":"Disorder","source_path":"kb/disorders/Schwannomatosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Schwannomatosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Schwannomatosis.html#dataset-geo-gse292071"}],"context_names":["Schwannoma","Schwannomatosis"],"disease_names":["Schwannoma","Schwannomatosis"],"disease_name":"Schwannoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Schwannoma.yaml","kb/disorders/Schwannomatosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Schwannoma.yaml","https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Schwannomatosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Schwannoma.html#dataset-geo-gse292071","https://dismech.monarchinitiative.org/pages/disorders/Schwannomatosis.html#dataset-geo-gse292071"]},{"id":"dataset:geo:gse292123","accession":"geo:GSE292123","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE292123","title":"Spatial transcriptomics analysis of urticarial rash skin from patients with Schnitzler syndrome","alternate_titles":[],"description":"We conducted a multicenter, open-label, single-arm phase II trial (SCan Study) to evaluate the efficacy and safety of canakinumab in 5 Japanese patients with Schnitzler syndrome (SchS), based on a similar study conducted in Germany. As part of this study, spatial transcriptomics of urticarial rash skin lesions were performed before treatment in 2 cases to identify IL1B-expressing cells. The spatial transcriptomics analysis was conducted using the 10x Genomics Xenium platform.","alternate_descriptions":[],"data_types":["SPATIAL_TRANSCRIPTOMICS"],"data_type_labels":["Spatially resolved transcriptomics"],"data_type_label":"Spatially resolved transcriptomics","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[10],"sample_count":10,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40393905"],"publication_contexts":[{"context_id":"disorder:Schnitzler_Syndrome","publication":"PMID:40393905"}],"publication":"PMID:40393905","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40393905","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Schnitzler Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Schnitzler_Syndrome","name":"Schnitzler Syndrome","kind":"Disorder","source_path":"kb/disorders/Schnitzler_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Schnitzler_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Schnitzler_Syndrome.html#dataset-geo-gse292123"}],"context_names":["Schnitzler Syndrome"],"disease_names":["Schnitzler Syndrome"],"disease_name":"Schnitzler Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Schnitzler_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Schnitzler_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Schnitzler_Syndrome.html#dataset-geo-gse292123"]},{"id":"dataset:geo:gse292189","accession":"geo:GSE292189","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE292189","title":"Single cell and clonal analysis of AL amyloidosis plasma cells and their bone marrow microenvironment","alternate_titles":[],"description":"AL amyloidosis is a disorder characterized by expansion of clonal plasma cells in the bone marrow and distant end organ damage mediated by misfolded immunoglobulin free light chains. There are currently limited data regarding the functional characteristics of AL amyloidosis plasma cells and their surrounding bone marrow microenvironment. We performed 5’ single cell RNA sequencing on 9 newly diagnosed, treatment naive AL amyloidosis patients and 8 healthy subjects. We identified generalized suppression of normal bone marrow hematopoiesis with distinct expansion of CD16 monocytes and subsets of CD4+ T cells in AL amyloidosis patients.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[52],"sample_count":52,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40493887"],"publication_contexts":[{"context_id":"disorder:AL_Amyloidosis","publication":"PMID:40493887"}],"publication":"PMID:40493887","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40493887","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Systemic AL Amyloidosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:AL_Amyloidosis","name":"Systemic AL Amyloidosis","kind":"Disorder","source_path":"kb/disorders/AL_Amyloidosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/AL_Amyloidosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Systemic_AL_Amyloidosis.html#dataset-geo-gse292189"}],"context_names":["Systemic AL Amyloidosis"],"disease_names":["Systemic AL Amyloidosis"],"disease_name":"Systemic AL Amyloidosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/AL_Amyloidosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/AL_Amyloidosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Systemic_AL_Amyloidosis.html#dataset-geo-gse292189"]},{"id":"dataset:geo:gse292315","accession":"geo:GSE292315","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE292315","title":"Effect of Fak1/Ptk2 knockout in a mouse model of NF2-related schwannomatosis","alternate_titles":[],"description":"NF2-related schwannomatosis (NF2-SWN) is a cancer predisposition syndrome characterized by the development of bilateral vestibular (VS) and spinal schwannomas. While benign, these tumors can cause significant morbidity and effective pharmacological treatments remain limited. Here we demonstrate that genetic ablation of focal adhesion kinase 1 (FAK1/PTK2) impairs tumor formation and preserves hearing in a murine model of NF2. Mechanistically, we show that Fak1 deletion decreases macrophage infiltration, attenuates NLRP3 inflammasome activation and suppresses the HGF-MET axis.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41616055"],"publication_contexts":[{"context_id":"disorder:Schwannomatosis","publication":"PMID:41616055"}],"publication":"PMID:41616055","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41616055","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Schwannomatosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Schwannomatosis","name":"Schwannomatosis","kind":"Disorder","source_path":"kb/disorders/Schwannomatosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Schwannomatosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Schwannomatosis.html#dataset-geo-gse292315"}],"context_names":["Schwannomatosis"],"disease_names":["Schwannomatosis"],"disease_name":"Schwannomatosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Schwannomatosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Schwannomatosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Schwannomatosis.html#dataset-geo-gse292315"]},{"id":"dataset:geo:gse292327","accession":"geo:GSE292327","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE292327","title":"Development, validation, and clinical utility of a novel methylation classifier for recurrence risk prediction in meningiomas","alternate_titles":[],"description":"DNA methylation profiling cohort used to develop and validate recurrence risk prediction models for meningioma.","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0010506","label":"meningeal dura mater","display_label":"meningioma tissue","url":"http://purl.obolibrary.org/obo/UBERON_0010506"}],"sample_type_labels":["meningeal dura mater"],"sample_counts":[223],"sample_count":223,"conditions":["meningioma","recurrence risk stratification"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41466325"],"publication_contexts":[{"context_id":"disorder:Meningioma","publication":"PMID:41466325"}],"publication":"PMID:41466325","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41466325","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:41466325","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41466325","reference_title":"Development, validation, and utility of a clinically applicable methylation classifier for recurrence risk prediction in meningiomas.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"Using samples from 217 patients, we developed, validated, and implemented a clinically applicable methylation classifier for prognostic stratification of meningiomas based on k-means clustering of methylation data.","explanation":"Supports the recurrence-risk methylation stratification intent of this dataset entry."}],"notes":["GEO metadata indicates a clinically validated recurrence-risk methylation classifier cohort."],"contexts":[{"id":"disorder:Meningioma","name":"Meningioma","kind":"Disorder","source_path":"kb/disorders/Meningioma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Meningioma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Meningioma.html#dataset-geo-gse292327"}],"context_names":["Meningioma"],"disease_names":["Meningioma"],"disease_name":"Meningioma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Meningioma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Meningioma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Meningioma.html#dataset-geo-gse292327"]},{"id":"dataset:geo:gse292394","accession":"geo:GSE292394","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE292394","title":"High-Resolution Spatial Map of the Human Facial Sebaceous Gland Reveals Marker Genes and Decodes Sebocyte Differentiation [MERFISH]","alternate_titles":[],"description":"Healthy human facial sebaceous-gland spatial and single-cell reference atlas used to interpret sebocyte differentiation; it is not an acne cohort.","alternate_descriptions":[],"data_types":["SPATIAL_TRANSCRIPTOMICS"],"data_type_labels":["Spatially resolved transcriptomics"],"data_type_label":"Spatially resolved transcriptomics","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[1],"sample_count":1,"conditions":["healthy facial skin"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE292394","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE292394","reference_title":"High-Resolution Spatial Map of the Human Facial Sebaceous Gland Reveals Marker Genes and Decodes Sebocyte Differentiation [MERFISH]","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"By integrating Stereo-seq spatial transcriptomics, single-cell RNA sequencing, and validation though MERFISH, we identified four distinct stages of sebocyte differentiation, each characterized by unique gene signatures.","explanation":"The GEO summary establishes this as a human sebocyte-differentiation reference atlas."}],"notes":[],"contexts":[{"id":"disorder:Acne_Vulgaris","name":"Acne Vulgaris","kind":"Disorder","source_path":"kb/disorders/Acne_Vulgaris.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Acne_Vulgaris.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Acne_Vulgaris.html#dataset-geo-gse292394"}],"context_names":["Acne Vulgaris"],"disease_names":["Acne Vulgaris"],"disease_name":"Acne Vulgaris","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Acne_Vulgaris.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Acne_Vulgaris.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Acne_Vulgaris.html#dataset-geo-gse292394"]},{"id":"dataset:geo:gse292448","accession":"geo:GSE292448","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE292448","title":"RNA profiles in extracellular vesicles from severe sepsis patients reveal pathogen-specific immune signatures in meningococcal versus pneumococcal infections","alternate_titles":[],"description":"This study is the first to investigate and compare RNA profiles in plasma extracellular vesicles (EVs) isolated from patients with severe sepsis caused by Neisseria meningitidis and patients with systemic infections due to Streptococcus pneumoniae. In some cases, invasive pneumococcal disease can resemble meningococcal infections at the time of hospital admission. Blood samples from a 1980s epidemic in Norway were used to isolate EVs and characterize their RNA content by microarray technology. The results revealed both shared and distinct RNA characteristics between the two patient groups, with 1,798 shared transcripts.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[21],"sample_count":21,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42112460"],"publication_contexts":[{"context_id":"disorder:Pneumococcal_Pneumonia","publication":"PMID:42112460"}],"publication":"PMID:42112460","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42112460","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Pneumococcal Pneumonia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Pneumococcal_Pneumonia","name":"Pneumococcal Pneumonia","kind":"Disorder","source_path":"kb/disorders/Pneumococcal_Pneumonia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pneumococcal_Pneumonia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pneumococcal_Pneumonia.html#dataset-geo-gse292448"}],"context_names":["Pneumococcal Pneumonia"],"disease_names":["Pneumococcal Pneumonia"],"disease_name":"Pneumococcal Pneumonia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Pneumococcal_Pneumonia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pneumococcal_Pneumonia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Pneumococcal_Pneumonia.html#dataset-geo-gse292448"]},{"id":"dataset:geo:gse292730","accession":"geo:GSE292730","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE292730","title":"Transcriptome Sequencing of Optic Nerve in a Rat Model of Neuromyelitis Optica Spectrum Disorder-Related Optic Neuritis (NMOSD-ON)","alternate_titles":[],"description":"This study established a rat model of NMOSD-ON by injecting patient-derived AQP4+ serum into the optic nerve sheath of rats. Optic nerve tissues were collected at 24 hours and 7 days post-modeling, along with a blank control group, for transcriptome sequencing. The aim was to explore gene expression changes during the early and peak phases of NMOSD-ON pathogenesis, thereby identifying potential disease mechanisms.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10116","label":"Rattus norvegicus","display_label":"rat","url":"http://purl.obolibrary.org/obo/NCBITaxon_10116"}],"organism_labels":["Rattus norvegicus"],"organism_label":"Rattus norvegicus","sample_types":[],"sample_type_labels":[],"sample_counts":[9],"sample_count":9,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Optic Neuritis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Optic_Neuritis","name":"Optic Neuritis","kind":"Disorder","source_path":"kb/disorders/Optic_Neuritis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Optic_Neuritis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Optic_Neuritis.html#dataset-geo-gse292730"}],"context_names":["Optic Neuritis"],"disease_names":["Optic Neuritis"],"disease_name":"Optic Neuritis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Optic_Neuritis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Optic_Neuritis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Optic_Neuritis.html#dataset-geo-gse292730"]},{"id":"dataset:geo:gse293154","accession":"geo:GSE293154","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE293154","title":"SETD1A Regulates Psychiatric Gene Networks Involved in Genomic Stability and Synaptic Function in Rare and Sporadic Schizophrenia [CUT&Tag]","alternate_titles":[],"description":"Rare loss-of-function (LoF) mutations in SETD1A are associated with schizophrenia (SCZ). However, how SETD1A haploinsufficiency leads to SCZ-associated phenotypes and its relevance to patients without these rare mutations is unknown. Here, we identify SETD1A bound loci and regulated genes in human prenatal cortex and isogenic pluripotent stem cell-derived neuronal models engineered with SETD1A LoF variants, including the most common patient mutation. SETD1A preferentially binds the promoters of SCZ and Bipolar risk loci that regulate chromatin remodeling, DNA repair, and synaptic function.","alternate_descriptions":[],"data_types":["ATAC_SEQ"],"data_type_labels":["Assay for transposase-accessible chromatin sequencing"],"data_type_label":"Assay for transposase-accessible chromatin sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[48],"sample_count":48,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41422157"],"publication_contexts":[{"context_id":"disorder:Schizophrenia","publication":"PMID:41422157"}],"publication":"PMID:41422157","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41422157","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Schizophrenia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Schizophrenia","name":"Schizophrenia","kind":"Disorder","source_path":"kb/disorders/Schizophrenia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Schizophrenia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Schizophrenia.html#dataset-geo-gse293154"}],"context_names":["Schizophrenia"],"disease_names":["Schizophrenia"],"disease_name":"Schizophrenia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Schizophrenia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Schizophrenia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Schizophrenia.html#dataset-geo-gse293154"]},{"id":"dataset:geo:gse293433","accession":"geo:GSE293433","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE293433","title":"Differential Expression and Correlation Analysis of Global Transcriptome for Obstructive Sleep Apnea Hypopnea Syndrome","alternate_titles":[],"description":"In order to investigate the gene expression patterns and molecular regulatory mechanisms of obstructive sleep apnea hypopnea syndrome (OSAHS), the global transcriptome expression profiles of OSAHS patients and healthy people were analyzed using transcriptome sequencing technology. Differential expression of circular RNA, microRNA, long noncoding RNA, and messenger RNA was investigated between the two groups.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[10],"sample_count":10,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40264951"],"publication_contexts":[{"context_id":"disorder:Obstructive_Sleep_Apnea","publication":"PMID:40264951"}],"publication":"PMID:40264951","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40264951","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Obstructive Sleep Apnea (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Obstructive_Sleep_Apnea","name":"Obstructive Sleep Apnea","kind":"Disorder","source_path":"kb/disorders/Obstructive_Sleep_Apnea.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Obstructive_Sleep_Apnea.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Obstructive_Sleep_Apnea.html#dataset-geo-gse293433"}],"context_names":["Obstructive Sleep Apnea"],"disease_names":["Obstructive Sleep Apnea"],"disease_name":"Obstructive Sleep Apnea","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Obstructive_Sleep_Apnea.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Obstructive_Sleep_Apnea.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Obstructive_Sleep_Apnea.html#dataset-geo-gse293433"]},{"id":"dataset:geo:gse29352","accession":"geo:GSE29352","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE29352","title":"miRNA expression profiles in Pancreatic Cystic tumours and Pancreatic Cancer","alternate_titles":[],"description":"MicroRNA (miRNA) expression profiles have been described in pancreatic ductal adenocarcinoma (PDAC), but these have not been compared with premalignant lesions. We wished to identify miRNA expression profiles in pancreatic cystic tumors with low malignant potential (serous microcystic adenomas) and high malignant potential (mucinous cystadenoma and intraductal papillary mucinous neoplasm (IPMN)) and compare these to PDAC and carcinoma-ex-IPMN (CEI).","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[43],"sample_count":43,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:22384141"],"publication_contexts":[{"context_id":"disorder:Pancreatic_Mucinous_Cystadenoma","publication":"PMID:22384141"}],"publication":"PMID:22384141","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/22384141","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Pancreatic Mucinous Cystadenoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Pancreatic_Mucinous_Cystadenoma","name":"Pancreatic Mucinous Cystadenoma","kind":"Disorder","source_path":"kb/disorders/Pancreatic_Mucinous_Cystadenoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pancreatic_Mucinous_Cystadenoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pancreatic_Mucinous_Cystadenoma.html#dataset-geo-gse29352"}],"context_names":["Pancreatic Mucinous Cystadenoma"],"disease_names":["Pancreatic Mucinous Cystadenoma"],"disease_name":"Pancreatic Mucinous Cystadenoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Pancreatic_Mucinous_Cystadenoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pancreatic_Mucinous_Cystadenoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Pancreatic_Mucinous_Cystadenoma.html#dataset-geo-gse29352"]},{"id":"dataset:geo:gse293648","accession":"geo:GSE293648","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE293648","title":"Gene expression profile of tibialis anterior from Gaa-/- mice compared to wild type mice","alternate_titles":[],"description":"Microarray profiling of tibialis anterior muscle from Gaa-knockout mice against wild type, generated in a study of membrane-repair proteins and satellite-cell failure in Pompe muscle. It is the transcriptomic layer of the same knockout model this entry curates under animal_models for the autophagic-buildup node.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"house mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[32],"sample_count":32,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:4065","label":"GAA","display_label":"GAA","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/4065"}],"genes":["GAA"],"platforms":[],"platform":null,"publications":["PMID:42337614"],"publication_contexts":[{"context_id":"disorder:Infantile-Onset_Pompe_Disease","publication":"PMID:42337614"}],"publication":"PMID:42337614","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42337614","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:42337614","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/42337614","reference_title":"Accumulation of membrane repair-associated proteins and mature myostatin are novel markers of muscle pathophysiology in Pompe disease.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"Longitudinal transcriptomic analysis of skeletal muscle from a Pompe disease mouse model, combined with immunohistochemical and biochemical approaches, showed early and sustained overexpression of dysferlin (DYSF), annexin A2 (ANXA2), and AHNAK2.","explanation":"Describes the transcriptomic analysis this dataset is the primary data for, and its principal result in the mouse muscle profiled."},{"reference":"PMID:42337614","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/42337614","reference_title":"Accumulation of membrane repair-associated proteins and mature myostatin are novel markers of muscle pathophysiology in Pompe disease.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"in the mouse model, we observed persistent post-transcriptional accumulation of mature myostatin (MSTN), a key negative regulator of muscle growth, alongside a decrease in the phospho-SMAD3/SMAD3 ratio and reduced SMAD7 expression","explanation":"Reports the second result obtained from this mouse model, a myostatin-axis change relevant to the muscle-wasting arm of the disease."}],"notes":["Discovered via `just discover-datasets` as a GENE_ONLY candidate and retained after manual relevance triage: the GEO title and summary describe Gaa-knockout mouse muscle with glycogen-filled lysosomes and autophagic build-up, which is this entry's mechanism. Relevance caveat: it is a mouse knockout, so it models GAA deficiency rather than the infantile onset or the cardiac severity that define IOPD, and the source publication's human validation arm is late-onset patients rather than infantile-onset ones. Verified with `just verify-datasets`. Retrieved 2026-09-01."],"contexts":[{"id":"disorder:Infantile-Onset_Pompe_Disease","name":"Infantile-Onset Pompe Disease","kind":"Disorder","source_path":"kb/disorders/Infantile-Onset_Pompe_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Infantile-Onset_Pompe_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Infantile-Onset_Pompe_Disease.html#dataset-geo-gse293648"}],"context_names":["Infantile-Onset Pompe Disease"],"disease_names":["Infantile-Onset Pompe Disease"],"disease_name":"Infantile-Onset Pompe Disease","same_context_model_ids":["model:kb/disorders/Infantile-Onset_Pompe_Disease.yaml:Patient-derived iPSC cardiomyocytes (PD-iCMs)"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Infantile-Onset_Pompe_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Infantile-Onset_Pompe_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Infantile-Onset_Pompe_Disease.html#dataset-geo-gse293648"]},{"id":"dataset:geo:gse293752","accession":"geo:GSE293752","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE293752","title":"IL4Ra blockade inhibits proliferation of malignant lymphocytes and the immunosuppressive tumor microenvironment of mycosis fungoides","alternate_titles":[],"description":"The IL4 and IL13 receptors are highly expressed in the mycosis fungoides (MF) cutaneous tumor microenvironment (TME). By combining single-cell RNA sequencing with inhibition of IL4Ra with Dupilumab (REGN668), a monoclonal antibody that targets the common subunit of the IL4 and IL13 receptors, we have identified the genes and pathways regulated by IL4/IL13 signaling in the MF TME. We found that Dupilumab inhibits patient-specific processes in malignant lymphocytes, and we also identified downregulation of common pathways among patient samples including those associated with cell cycle progression, PI3K/AKT signaling, JAK/STAT signaling, DNA damage/repair, and TP53 regulation.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[23],"sample_count":23,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42350047"],"publication_contexts":[{"context_id":"disorder:Mycosis_Fungoides","publication":"PMID:42350047"}],"publication":"PMID:42350047","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42350047","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Mycosis Fungoides (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Mycosis_Fungoides","name":"Mycosis Fungoides","kind":"Disorder","source_path":"kb/disorders/Mycosis_Fungoides.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mycosis_Fungoides.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Mycosis_Fungoides.html#dataset-geo-gse293752"}],"context_names":["Mycosis Fungoides"],"disease_names":["Mycosis Fungoides"],"disease_name":"Mycosis Fungoides","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Mycosis_Fungoides.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mycosis_Fungoides.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Mycosis_Fungoides.html#dataset-geo-gse293752"]},{"id":"dataset:geo:gse293840","accession":"geo:GSE293840","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE293840","title":"Circulating cell-free RNA signatures for the characterization and diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)","alternate_titles":[],"description":"People living with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) experience heterogeneous and debilitating symptoms that lack sufficient biological explanation, compounded by the absence of accurate, noninvasive diagnostic tools. To address these challenges, we explored circulating cell-free RNA (cfRNA) as a blood-borne bioanalyte to monitor ME/CFS. cfRNA is released into the bloodstream during cellular turnover and reflects dynamic changes in gene expression, cellular signaling, and tissue-specific processes.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[168],"sample_count":168,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40789036"],"publication_contexts":[{"context_id":"disorder:Myalgic_Encephalomyelitis_Chronic_Fatigue_Syndrome","publication":"PMID:40789036"}],"publication":"PMID:40789036","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40789036","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values. Accession reverified on 2026-09-04. Dataset records or repeated samples are not necessarily independent participants. Provider-report citation does not establish that OpenScientist downloaded or analyzed this dataset."],"contexts":[{"id":"disorder:Myalgic_Encephalomyelitis_Chronic_Fatigue_Syndrome","name":"Myalgic Encephalomyelitis/Chronic Fatigue Syndrome","kind":"Disorder","source_path":"kb/disorders/Myalgic_Encephalomyelitis_Chronic_Fatigue_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myalgic_Encephalomyelitis_Chronic_Fatigue_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Myalgic_Encephalomyelitis_Chronic_Fatigue_Syndrome.html#dataset-geo-gse293840"}],"context_names":["Myalgic Encephalomyelitis/Chronic Fatigue Syndrome"],"disease_names":["Myalgic Encephalomyelitis/Chronic Fatigue Syndrome"],"disease_name":"Myalgic Encephalomyelitis/Chronic Fatigue Syndrome","same_context_model_ids":["model:kb/disorders/Myalgic_Encephalomyelitis_Chronic_Fatigue_Syndrome.yaml:Erythrocyte Microfluidic Deformability Assay","model:kb/disorders/Myalgic_Encephalomyelitis_Chronic_Fatigue_Syndrome.yaml:Patient NK-Cell TRPM3 Assays","model:kb/disorders/Myalgic_Encephalomyelitis_Chronic_Fatigue_Syndrome.yaml:Patient Serum Vesicle-Microglia Assay","model:kb/disorders/Myalgic_Encephalomyelitis_Chronic_Fatigue_Syndrome.yaml:Patient T-Cell Metabolic Assays","model:kb/disorders/Myalgic_Encephalomyelitis_Chronic_Fatigue_Syndrome.yaml:Patient-Derived Skeletal Myotubes"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Myalgic_Encephalomyelitis_Chronic_Fatigue_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myalgic_Encephalomyelitis_Chronic_Fatigue_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Myalgic_Encephalomyelitis_Chronic_Fatigue_Syndrome.html#dataset-geo-gse293840"]},{"id":"dataset:geo:gse293872","accession":"geo:GSE293872","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE293872","title":"Gene expression and V(D)J profiles of B-lineage cells from bone marrow samples of healthy adults (HA) and patients with multiple myeloma (MM)  and light-chain amyloidosis (AL).","alternate_titles":[],"description":"We employed single-cell RNA sequencing combined with BCR sequencing (scRNA/BCR-seq) to identify transcriptional differences between clonal B cells and non-clonal B cells from MM and AL patients versus their healthy counterparts.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[38],"sample_count":38,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41812162"],"publication_contexts":[{"context_id":"disorder:Amyloidosis","publication":"PMID:41812162"}],"publication":"PMID:41812162","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41812162","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Amyloidosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Amyloidosis","name":"Amyloidosis","kind":"Disorder","source_path":"kb/disorders/Amyloidosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Amyloidosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Amyloidosis.html#dataset-geo-gse293872"}],"context_names":["Amyloidosis"],"disease_names":["Amyloidosis"],"disease_name":"Amyloidosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Amyloidosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Amyloidosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Amyloidosis.html#dataset-geo-gse293872"]},{"id":"dataset:geo:gse294009","accession":"geo:GSE294009","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE294009","title":"Spatial Transcriptomic Analysis of Early and Late Stages of Hidradenitis Suppurativa","alternate_titles":[],"description":"Spatial transcriptomics of early and late HS skin lesions characterizing inflammatory nodules, abscess formation, and sinus tract development at spatial resolution.","alternate_descriptions":[],"data_types":["SPATIAL_TRANSCRIPTOMICS"],"data_type_labels":["Spatially resolved transcriptomics"],"data_type_label":"Spatially resolved transcriptomics","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[204],"sample_count":204,"conditions":["early-stage HS lesions","late-stage HS lesions"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Large spatial transcriptomics dataset (204 samples) comparing early and late HS stages."],"contexts":[{"id":"disorder:Hidradenitis_Suppurativa","name":"Hidradenitis Suppurativa","kind":"Disorder","source_path":"kb/disorders/Hidradenitis_Suppurativa.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hidradenitis_Suppurativa.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hidradenitis_Suppurativa.html#dataset-geo-gse294009"}],"context_names":["Hidradenitis Suppurativa"],"disease_names":["Hidradenitis Suppurativa"],"disease_name":"Hidradenitis Suppurativa","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hidradenitis_Suppurativa.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hidradenitis_Suppurativa.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hidradenitis_Suppurativa.html#dataset-geo-gse294009"]},{"id":"dataset:geo:gse294074","accession":"geo:GSE294074","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE294074","title":"CNOT6L regulates energy metabolism in the ovarian granulosa cells associated with polycystic ovary syndrome.","alternate_titles":[],"description":"As somatic cells surround the oocyte, the endocrine functions exerted by ovarian granulosa cells (GCs) are crucial factors in maintaining follicle development, as oocyte development relies on the provision of energy substrates and cytokines by ovarian granulosa cells. The mRNA deadenylase level of granulosa cells precisely regulates the transcription processes of key molecules involved in oocyte maturation. In this study, we detect the expression level of the deadenylase CNOT6L in PCOS patients' granulosa cells and mouse models' ovaries. We found that the CNOT6L significantly upregulated in the ovarian granulosa cells of both PCOS patients and mouse models.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40458121"],"publication_contexts":[{"context_id":"disorder:Polycystic_Ovary_Syndrome","publication":"PMID:40458121"}],"publication":"PMID:40458121","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40458121","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Polycystic Ovary Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Polycystic_Ovary_Syndrome","name":"Polycystic Ovary Syndrome","kind":"Disorder","source_path":"kb/disorders/Polycystic_Ovary_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Polycystic_Ovary_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Polycystic_Ovary_Syndrome.html#dataset-geo-gse294074"}],"context_names":["Polycystic Ovary Syndrome"],"disease_names":["Polycystic Ovary Syndrome"],"disease_name":"Polycystic Ovary Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Polycystic_Ovary_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Polycystic_Ovary_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Polycystic_Ovary_Syndrome.html#dataset-geo-gse294074"]},{"id":"dataset:geo:gse294284","accession":"geo:GSE294284","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE294284","title":"Transcriptomic Profiling of Zebrafish Mutant for cdkl5 Reveals Dysregulated Gene Expression Associated with Neuronal and Skeletal Development","alternate_titles":[],"description":"Whole-animal RNA sequencing of homozygous cdkl5sa21938 zebrafish and wild-type siblings at 5 and 35 days postfertilization, with five pooled biological replicates per genotype and age (20 samples). Pools contain 50 larvae or seven juveniles. These data sample neural and non-neural tissues and cannot localize an expression change to a specific cell type.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:7955","label":"Danio rerio","display_label":"zebrafish","url":"http://purl.obolibrary.org/obo/NCBITaxon_7955"}],"organism_labels":["Danio rerio"],"organism_label":"Danio rerio","sample_types":[],"sample_type_labels":[],"sample_counts":[20],"sample_count":20,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:11411","label":"CDKL5","display_label":"CDKL5","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/11411"}],"genes":["CDKL5"],"platforms":[],"platform":null,"publications":["PMID:40649845"],"publication_contexts":[{"context_id":"disorder:CDKL5_Deficiency_Disorder","publication":"PMID:40649845"}],"publication":"PMID:40649845","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40649845","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Accession, title, organism and sample count verified against the fetched GEO record on 2026-10-01. Interpret expression changes with the study design and model limitations described here. The gene descriptor identifies the human disease gene; the perturbed zebrafish ortholog is cdkl5."],"contexts":[{"id":"disorder:CDKL5_Deficiency_Disorder","name":"CDKL5 Deficiency Disorder","kind":"Disorder","source_path":"kb/disorders/CDKL5_Deficiency_Disorder.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/CDKL5_Deficiency_Disorder.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/CDKL5_Deficiency_Disorder.html#dataset-geo-gse294284"}],"context_names":["CDKL5 Deficiency Disorder"],"disease_names":["CDKL5 Deficiency Disorder"],"disease_name":"CDKL5 Deficiency Disorder","same_context_model_ids":["model:kb/disorders/CDKL5_Deficiency_Disorder.yaml:CLIP170-Dynactin and Cargo Transport Assays","model:kb/disorders/CDKL5_Deficiency_Disorder.yaml:Isogenic R59Ter Neuronal Phosphoproteomics","model:kb/disorders/CDKL5_Deficiency_Disorder.yaml:MAP1S Microtubule Dynamics and Rescue Assays","model:kb/disorders/CDKL5_Deficiency_Disorder.yaml:NGN2-Induced Patient Neurons","model:kb/disorders/CDKL5_Deficiency_Disorder.yaml:Patient-Derived Cortical Organoid Neurons","model:kb/disorders/CDKL5_Deficiency_Disorder.yaml:Postsynaptic Condensate Reconstitution","model:kb/disorders/CDKL5_Deficiency_Disorder.yaml:R550Ter Patient iPSC Base-Editing Rescue"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/CDKL5_Deficiency_Disorder.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/CDKL5_Deficiency_Disorder.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/CDKL5_Deficiency_Disorder.html#dataset-geo-gse294284"]},{"id":"dataset:geo:gse294485","accession":"geo:GSE294485","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE294485","title":"Klinefelter Syndrome: a neurodevelopmental disease of the synapse","alternate_titles":[],"description":"Klinefelter syndrome (KS; 47, XXY) is the most common sex chromosome disorder, affecting approximately 1 in every 500 to 650 newborn males. Children with KS display a spectrum of phenotypic manifestations, including abnormal neurocognitive phenotypes. However, due to the limited research focusing on the central nervous system (CNS), our understanding of the neurobiology of KS at the cellular and molecular levels remains largely unclear. In this study, we utilized brain organoids derived from pluripotent stem cells to explore the mechanisms underlying early brain developmental defects in KS patients.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40578768"],"publication_contexts":[{"context_id":"disorder:Klinefelter_Syndrome","publication":"PMID:40578768"}],"publication":"PMID:40578768","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40578768","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Klinefelter Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Klinefelter_Syndrome","name":"Klinefelter Syndrome","kind":"Disorder","source_path":"kb/disorders/Klinefelter_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Klinefelter_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Klinefelter_Syndrome.html#dataset-geo-gse294485"}],"context_names":["Klinefelter Syndrome"],"disease_names":["Klinefelter Syndrome"],"disease_name":"Klinefelter Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association 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pathway genes.","evidence":[{"reference":"geo:GSE294755","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE294755","reference_title":"Whole transcriptome comparison between two groups of PKU patients: Non-carriers vs. Carriers of rs113883650","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We demonstrated a decrease of expression of proteasome pathway (KEGG) incells treated with high Phe concentrations.","explanation":"GEO summary reports pathway-level transcriptomic changes under high phenylalanine exposure."}]}],"findings_text":["High-phenylalanine conditions in this cohort were associated with reduced expression of proteasome pathway genes."],"evidence":[{"reference":"geo:GSE294755","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE294755","reference_title":"Whole transcriptome comparison between two groups of PKU patients: Non-carriers vs. Carriers of rs113883650","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We demonstrated a decrease of expression of proteasome pathway (KEGG) incells treated with high Phe concentrations.","explanation":"Dataset-level summary supports relevance to PKU high-phenylalanine cellular response."}],"notes":[],"contexts":[{"id":"disorder:Phenylketonuria","name":"Phenylketonuria","kind":"Disorder","source_path":"kb/disorders/Phenylketonuria.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Phenylketonuria.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Phenylketonuria.html#dataset-geo-gse294755"}],"context_names":["Phenylketonuria"],"disease_names":["Phenylketonuria"],"disease_name":"Phenylketonuria","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association 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Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis, anti-glomerular basement membrane (anti-GBM) and lupus nephritis are the most common causes of RPGN and are characterized by the formation of glomerular crescents and infiltration of leukocytes that eventually lead to glomerulosclerosis and kidney failure.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[9],"sample_count":9,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40393992"],"publication_contexts":[{"context_id":"disorder:Anti-GBM_Disease","publication":"PMID:40393992"}],"publication":"PMID:40393992","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40393992","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Anti-Glomerular Basement Membrane Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Anti-GBM_Disease","name":"Anti-Glomerular Basement Membrane Disease","kind":"Disorder","source_path":"kb/disorders/Anti-GBM_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Anti-GBM_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Anti-Glomerular_Basement_Membrane_Disease.html#dataset-geo-gse294965"}],"context_names":["Anti-Glomerular Basement Membrane Disease"],"disease_names":["Anti-Glomerular Basement Membrane Disease"],"disease_name":"Anti-Glomerular Basement Membrane Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Anti-GBM_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Anti-GBM_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Anti-Glomerular_Basement_Membrane_Disease.html#dataset-geo-gse294965"]},{"id":"dataset:geo:gse295056","accession":"geo:GSE295056","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE295056","title":"Gene-Gene Interactions Between A LMNA Variant and Common Polymorphisms Drive Early-Onset Atrial Fibrillation [ATAC-seq]","alternate_titles":[],"description":"Atrial fibrillation (AF) is a common arrhythmia with a complex genetic basis, yet the molecular mechanisms linking rare and common variants remain unclear. Using induced pluripotent stem cell-derived atrial cardiomyocytes, we uncover a novel mechanism by which a rare pathogenic LMNA variant encoding Lamin A/C disrupts chromatin accessibility and gene regulation at AF-associated loci. Specifically, reduced accessibility at an SCN5A enhancer harboring an AF-associated variant leads to reduced sodium current, conduction abnormalities, and re-entrant AF.","alternate_descriptions":[],"data_types":["ATAC_SEQ"],"data_type_labels":["Assay for transposase-accessible chromatin sequencing"],"data_type_label":"Assay for transposase-accessible chromatin sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[9],"sample_count":9,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42156780"],"publication_contexts":[{"context_id":"disorder:Atrial_Fibrillation","publication":"PMID:42156780"},{"context_id":"disorder:Familial_Atrial_Fibrillation","publication":"PMID:42156780"}],"publication":"PMID:42156780","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42156780","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Atrial Fibrillation (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values.","Identified by GEO DataSets index search for Familial Atrial Fibrillation (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Atrial_Fibrillation","name":"Atrial Fibrillation","kind":"Disorder","source_path":"kb/disorders/Atrial_Fibrillation.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Atrial_Fibrillation.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Atrial_Fibrillation.html#dataset-geo-gse295056"},{"id":"disorder:Familial_Atrial_Fibrillation","name":"Familial Atrial Fibrillation","kind":"Disorder","source_path":"kb/disorders/Familial_Atrial_Fibrillation.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Familial_Atrial_Fibrillation.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Familial_Atrial_Fibrillation.html#dataset-geo-gse295056"}],"context_names":["Atrial Fibrillation","Familial Atrial Fibrillation"],"disease_names":["Atrial Fibrillation","Familial Atrial Fibrillation"],"disease_name":"Atrial Fibrillation","same_context_model_ids":["model:kb/disorders/Atrial_Fibrillation.yaml:Palmitate-treated human iPSC-derived atrial cardiomyocytes"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Atrial_Fibrillation.yaml","kb/disorders/Familial_Atrial_Fibrillation.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Atrial_Fibrillation.yaml","https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Familial_Atrial_Fibrillation.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Atrial_Fibrillation.html#dataset-geo-gse295056","https://dismech.monarchinitiative.org/pages/disorders/Familial_Atrial_Fibrillation.html#dataset-geo-gse295056"]},{"id":"dataset:geo:gse295078","accession":"geo:GSE295078","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE295078","title":"Single-nucleus transcriptomics of inducible Ngly1-/- cerebellum","alternate_titles":[],"description":"Single-nucleus RNA sequencing of cerebella from Ngly1fl/fl, iNgly1-/- and iNgly1-/-Sting1-/- mice, examining cell-type-specific effects of NGLY1 deficiency and the contribution of the STING pathway. The Sting1 double knockout arm is what makes the series informative rather than descriptive: it tests whether an inflammatory pathway mediates the neurodegeneration.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40644312"],"publication_contexts":[{"context_id":"disorder:NGLY1-congenital_disorder_of_deglycosylation","publication":"PMID:40644312"}],"publication":"PMID:40644312","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40644312","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Found by GEO DataSets search and verified against NCBI E-utilities on 2026-08-20. DIRECT relevance - an Ngly1 knockout series in the inducible mouse model this entry curates. The associated publication (PMID:40644312, STING-driven noninflammatory neurodegeneration) is not yet curated as evidence in this entry; the dataset is recorded here without inheriting any claim from it."],"contexts":[{"id":"disorder:NGLY1-congenital_disorder_of_deglycosylation","name":"NGLY1-congenital disorder of deglycosylation","kind":"Disorder","source_path":"kb/disorders/NGLY1-congenital_disorder_of_deglycosylation.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/NGLY1-congenital_disorder_of_deglycosylation.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/NGLY1-congenital_disorder_of_deglycosylation.html#dataset-geo-gse295078"}],"context_names":["NGLY1-congenital disorder of deglycosylation"],"disease_names":["NGLY1-congenital disorder of deglycosylation"],"disease_name":"NGLY1-congenital disorder of deglycosylation","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/NGLY1-congenital_disorder_of_deglycosylation.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/NGLY1-congenital_disorder_of_deglycosylation.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/NGLY1-congenital_disorder_of_deglycosylation.html#dataset-geo-gse295078"]},{"id":"dataset:geo:gse295480","accession":"geo:GSE295480","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE295480","title":"Ototoxicity-induced c-Fos activation underlies regenerative capacity in vestibular sensory epithelia","alternate_titles":[],"description":"RNA sequencing of neonatal mouse utricle vestibular sensory epithelia examining the role of c-Fos activation in vestibular hair cell regeneration following gentamicin-induced ototoxic injury. 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Whether age-related changes in immune cells, termed immunosenescence, contribute to BPH is not clear. Specific T cell populations, in particular a subset of CD8+ T cells with high Granzyme K (GZMKhi) and low Granzyme B (GZMBlow) gene expression, have been associated with aging; however, the precise function and biological significance of these cells in age-related diseases is not known. The current study determine that Taa cells infiltrate aged human prostates and positively correlate with International Prostate Symptom Score (IPSS).","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[17],"sample_count":17,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40692782"],"publication_contexts":[{"context_id":"disorder:Benign_Prostatic_Hyperplasia","publication":"PMID:40692782"}],"publication":"PMID:40692782","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40692782","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Benign Prostatic Hyperplasia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Benign_Prostatic_Hyperplasia","name":"Benign Prostatic Hyperplasia","kind":"Disorder","source_path":"kb/disorders/Benign_Prostatic_Hyperplasia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Benign_Prostatic_Hyperplasia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Benign_Prostatic_Hyperplasia.html#dataset-geo-gse295879"}],"context_names":["Benign Prostatic Hyperplasia"],"disease_names":["Benign Prostatic Hyperplasia"],"disease_name":"Benign Prostatic Hyperplasia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Benign_Prostatic_Hyperplasia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Benign_Prostatic_Hyperplasia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Benign_Prostatic_Hyperplasia.html#dataset-geo-gse295879"]},{"id":"dataset:geo:gse295975","accession":"geo:GSE295975","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE295975","title":"2,8-Dihydroxyadenine disrupts epithelial integrity and alters kidney cell phenotype in vitro","alternate_titles":[],"description":"Adenine phosphoribosyltransferase (APRT) deficiency is an autosomal recessive disorder that causes accumulation of 2,8-dihydroxyadenine (DHA) in the urinary tract, leading to kidney stones and chronic kidney disease. Progression to end-stage kidney disease can occur without timely treatment. The xanthine oxidoreductase inhibitors, allopurinol and febuxostat, block DHA generation and halt or delay stone formation and disease progression. Some patients cannot tolerate these drugs, necessitating new therapeutic approaches. This study aimed to investigate how DHA influences structural and molecular changes in HK-2, HEK293, and MDCK kidney cells.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Adenine Phosphoribosyltransferase Deficiency (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Adenine_Phosphoribosyltransferase_Deficiency","name":"Adenine Phosphoribosyltransferase Deficiency","kind":"Disorder","source_path":"kb/disorders/Adenine_Phosphoribosyltransferase_Deficiency.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Adenine_Phosphoribosyltransferase_Deficiency.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Adenine_Phosphoribosyltransferase_Deficiency.html#dataset-geo-gse295975"}],"context_names":["Adenine Phosphoribosyltransferase Deficiency"],"disease_names":["Adenine Phosphoribosyltransferase Deficiency"],"disease_name":"Adenine Phosphoribosyltransferase Deficiency","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Adenine_Phosphoribosyltransferase_Deficiency.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Adenine_Phosphoribosyltransferase_Deficiency.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Adenine_Phosphoribosyltransferase_Deficiency.html#dataset-geo-gse295975"]},{"id":"dataset:geo:gse296077","accession":"geo:GSE296077","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE296077","title":"Metabolic Reprogramming during Human Neuron Differentiation Identifies Glutaminase as a Key Determinant in Fragile X Syndrome","alternate_titles":[],"description":"Metabolic homeostasis gone awry is a contributor to, if not an underlying cause of, several neurologic disorders. Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by a trinucleotide repeat expansion in FMR1 and consequent loss of the encoded protein FMRP, which results in downstream molecular, neurologic, and mitochondrial deficits that are linked to cognitive impairment. In human postmortem brain, many metabolites and solute carrier proteins are coordinately dysregulated, which also occurs during differentiation of human iPSCs into excitatory neurons.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[10],"sample_count":10,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41557506"],"publication_contexts":[{"context_id":"disorder:Fragile_X_Syndrome","publication":"PMID:41557506"}],"publication":"PMID:41557506","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41557506","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Fragile X Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Fragile_X_Syndrome","name":"Fragile X Syndrome","kind":"Disorder","source_path":"kb/disorders/Fragile_X_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fragile_X_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Fragile_X_Syndrome.html#dataset-geo-gse296077"}],"context_names":["Fragile X Syndrome"],"disease_names":["Fragile X Syndrome"],"disease_name":"Fragile X Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Fragile_X_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fragile_X_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Fragile_X_Syndrome.html#dataset-geo-gse296077"]},{"id":"dataset:geo:gse296198","accession":"geo:GSE296198","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE296198","title":"Chronic circadian misalignment accelerates sarcopenia progression in mice","alternate_titles":[],"description":"Bulk RNA-seq testing circadian misalignment as an accelerant of sarcopenia progression; the largest of the candidate mouse datasets.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[30],"sample_count":30,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41321491"],"publication_contexts":[{"context_id":"disorder:Sarcopenia","publication":"PMID:41321491"}],"publication":"PMID:41321491","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41321491","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Mouse data. Selected by manual relevance triage and accession-verified. Candidates rejected in triage: geo:GSE279051 (cortical bone metabolism, not muscle), geo:GSE276208 (sarcopenia as the exposure driving tumorigenesis, not the subject), and geo:GSE304351 / geo:GSE304464 / geo:GSE315575, which name sarcopenia only in the summary and study muscle atrophy or lifespan more broadly. No evidence block, as above."],"contexts":[{"id":"disorder:Sarcopenia","name":"Sarcopenia","kind":"Disorder","source_path":"kb/disorders/Sarcopenia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sarcopenia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Sarcopenia.html#dataset-geo-gse296198"}],"context_names":["Sarcopenia"],"disease_names":["Sarcopenia"],"disease_name":"Sarcopenia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Sarcopenia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sarcopenia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Sarcopenia.html#dataset-geo-gse296198"]},{"id":"dataset:geo:gse296546","accession":"geo:GSE296546","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE296546","title":"Diabetes mellitus is associated with a shared hyper-inflammatory immune response in melioidosis and tuberculosis patients: an observational case-control study","alternate_titles":[],"description":"Melioidosis is a serious infection caused by the bacterium Burkholderia pseudomallei (Bp) with a case fatality rate of up to 40% in Northeast Thailand. Diabetes increases the risk of developing melioidosis by 12-fold. A similar, but less marked, relationship with diabetes is seen in tuberculosis (TB) patients, with a 3-fold increased risk of developing TB in people with diabetes. However, the mechanisms underlying increased susceptibility are not fully understood. Whole blood samples of 81 acute melioidosis patients from Northeast Thailand and 151 TB patients from South Africa, Indonesia, Romania and Peru alongside uninfected control cohorts were studied by whole blood RNA sequencing.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[110],"sample_count":110,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42318305"],"publication_contexts":[{"context_id":"disorder:Tuberculosis","publication":"PMID:42318305"}],"publication":"PMID:42318305","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42318305","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Tuberculosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Tuberculosis","name":"Tuberculosis","kind":"Disorder","source_path":"kb/disorders/Tuberculosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Tuberculosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Tuberculosis.html#dataset-geo-gse296546"}],"context_names":["Tuberculosis"],"disease_names":["Tuberculosis"],"disease_name":"Tuberculosis","same_context_model_ids":["model:kb/disorders/Tuberculosis.yaml:Autologous iPSC-derived alveolus-on-chip (iLoC) Mtb infection model"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Tuberculosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Tuberculosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Tuberculosis.html#dataset-geo-gse296546"]},{"id":"dataset:geo:gse296560","accession":"geo:GSE296560","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE296560","title":"Lupus nephritis serum induces changes in gene expression in human glomerular endothelial cells, which is modulated by L-sepiapterin: Implications for redox-mediated endothelial dysfunction","alternate_titles":[],"description":"Lupus nephritis (LN) is characterized by renal endothelial dysfunction, which contributes to progressive kidney injury. Endothelial nitric oxide synthase (eNOS) plays a modulating role in LN, as genetic ablation of the eNOS enzyme worsens disease. Serum from patients with active LN induces uncoupling of eNOS homodimers, leading to superoxide (SO) rather than nitric oxide (NO) production by eNOS. This uncoupling is reversed with L-sepiapterin (L-Sep). This study was designed to further examine changes in gene expression in glomerular endothelial cells induced by LN serum and whether treatment with L-Sep can ameliorate these changes.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[19],"sample_count":19,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40480647"],"publication_contexts":[{"context_id":"disorder:Lupus_Nephritis","publication":"PMID:40480647"}],"publication":"PMID:40480647","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40480647","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Lupus Nephritis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Lupus_Nephritis","name":"Lupus Nephritis","kind":"Disorder","source_path":"kb/disorders/Lupus_Nephritis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Lupus_Nephritis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Lupus_Nephritis.html#dataset-geo-gse296560"}],"context_names":["Lupus Nephritis"],"disease_names":["Lupus Nephritis"],"disease_name":"Lupus Nephritis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Lupus_Nephritis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Lupus_Nephritis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Lupus_Nephritis.html#dataset-geo-gse296560"]},{"id":"dataset:geo:gse296628","accession":"geo:GSE296628","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE296628","title":"Brown remodeling of white adipose tissue protects against abdominal aortic aneurysm via a novel batokine FSTL1","alternate_titles":[],"description":"Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease without effective medical therapies. Emerging evidences have suggested a crosstalk between adipose tissue and vascular cells and brown adipose tissue is beneficial for cardiovascular health. Nevertheless, whether brown remodeling of white adipose tissue would protect against AAA remains unclear. Here we showed that patients with AAA had a decreased browning level of adipose tissue and induction of adipose tissue browning significantly reduced AAA incidence and attenuated AAA development in mice.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41068431"],"publication_contexts":[{"context_id":"disorder:Abdominal_Aortic_Aneurysm","publication":"PMID:41068431"}],"publication":"PMID:41068431","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41068431","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Abdominal Aortic Aneurysm (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Abdominal_Aortic_Aneurysm","name":"Abdominal Aortic Aneurysm","kind":"Disorder","source_path":"kb/disorders/Abdominal_Aortic_Aneurysm.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Abdominal_Aortic_Aneurysm.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Abdominal_Aortic_Aneurysm.html#dataset-geo-gse296628"}],"context_names":["Abdominal Aortic Aneurysm"],"disease_names":["Abdominal Aortic Aneurysm"],"disease_name":"Abdominal Aortic Aneurysm","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Abdominal_Aortic_Aneurysm.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Abdominal_Aortic_Aneurysm.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Abdominal_Aortic_Aneurysm.html#dataset-geo-gse296628"]},{"id":"dataset:geo:gse296978","accession":"geo:GSE296978","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE296978","title":"H4K16 acylations fine-tune transcriptional response to short-chain acyl-CoA dehydrogenase deficiency (RNA-seq)","alternate_titles":[],"description":"Bulk RNA-seq of wild-type versus Acads-deficient (SCADD) mouse liver, linking accumulating short-chain acyl-CoAs to histone H4K16 acylation and transcriptional remodeling — an epigenetic consequence of the SCAD metabolic block.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41421336"],"publication_contexts":[{"context_id":"disorder:SCAD_Deficiency","publication":"PMID:41421336"}],"publication":"PMID:41421336","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41421336","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Organism: mouse (Mus musculus), male liver. NCBI GEO subseries (companion GSE296977 ChIP-seq, GSE296976 ATAC-seq)."],"contexts":[{"id":"disorder:SCAD_Deficiency","name":"Short-Chain Acyl-CoA Dehydrogenase Deficiency","kind":"Disorder","source_path":"kb/disorders/SCAD_Deficiency.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/SCAD_Deficiency.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Short-Chain_Acyl-CoA_Dehydrogenase_Deficiency.html#dataset-geo-gse296978"}],"context_names":["Short-Chain Acyl-CoA Dehydrogenase Deficiency"],"disease_names":["Short-Chain Acyl-CoA Dehydrogenase Deficiency"],"disease_name":"Short-Chain Acyl-CoA Dehydrogenase Deficiency","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/SCAD_Deficiency.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/SCAD_Deficiency.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Short-Chain_Acyl-CoA_Dehydrogenase_Deficiency.html#dataset-geo-gse296978"]},{"id":"dataset:geo:gse297386","accession":"geo:GSE297386","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE297386","title":"Vitamin D Enhances Antiviral Responses in Dengue Virus-Infected Macrophages by Modulating Early-Response Gene Expression","alternate_titles":[],"description":"Dengue virus (DENV), the etiological agent of dengue fever, remains a global health concern, leading to severe illness and death in the absence of any definitive cure. Research has shown that vitamin D may reduce DENV replication in vitro and that dengue patients with low or deficient vitamin D levels are at higher risk of severe dengue. Studies indicate that viral replication is inhibited in human monocyte-derived macrophages (MDM) differentiated in the presence of vitamin D (D3MDM), suggesting that vitamin D may prevent DENV entry into host cells.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[24],"sample_count":24,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40839599"],"publication_contexts":[{"context_id":"disorder:Dengue","publication":"PMID:40839599"}],"publication":"PMID:40839599","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40839599","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Dengue (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Dengue","name":"Dengue","kind":"Disorder","source_path":"kb/disorders/Dengue.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dengue.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Dengue.html#dataset-geo-gse297386"}],"context_names":["Dengue"],"disease_names":["Dengue"],"disease_name":"Dengue","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Dengue.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dengue.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Dengue.html#dataset-geo-gse297386"]},{"id":"dataset:geo:gse297566","accession":"geo:GSE297566","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE297566","title":"Hippocampal epitranscriptomic (m6A) in human model of Temporal Lobe Epilepsy","alternate_titles":[],"description":"Analogous to DNA methylation and protein phosphorylation it is now well understood that RNA is also subject to extensive processing and modification. N6-methyladenosine (m6A) is the most abundant internal RNA modification and regulates RNA fate in several ways including stability and translational efficiency. The role of m6A in both experimental and human epilepsy remains unknown. Here we use transcriptome-wide m6A arrays to obtain a detailed analysis of the hippocampal m6A-ome from human temporal lobe epilepsy samples. We show that epileptic tissue displays disrupted metabolic and autophagic pathways which may be directly linked to m6A-processing.","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[48],"sample_count":48,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40693462"],"publication_contexts":[{"context_id":"disorder:Temporal_Lobe_Epilepsy","publication":"PMID:40693462"}],"publication":"PMID:40693462","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40693462","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Temporal Lobe Epilepsy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Temporal_Lobe_Epilepsy","name":"Temporal Lobe Epilepsy","kind":"Disorder","source_path":"kb/disorders/Temporal_Lobe_Epilepsy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Temporal_Lobe_Epilepsy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Temporal_Lobe_Epilepsy.html#dataset-geo-gse297566"}],"context_names":["Temporal Lobe Epilepsy"],"disease_names":["Temporal Lobe Epilepsy"],"disease_name":"Temporal Lobe Epilepsy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Temporal_Lobe_Epilepsy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Temporal_Lobe_Epilepsy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Temporal_Lobe_Epilepsy.html#dataset-geo-gse297566"]},{"id":"dataset:geo:gse297679","accession":"geo:GSE297679","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE297679","title":"Elevated FTO alleviates sepsis-induced acute kidney injury by regulating macrophage inflammatory phenotypes [MeRIP-seq]","alternate_titles":[],"description":"Recent studies have linked the dysregulation of N6-methyladenosine (m6A) to sepsis-induced acute kidney injury (SAKI), highlighting the persistent challenge of managing excessive proinflammatory cytokine production and subsequent organ dysfunction. In this study, we analyzed the dataset GSE32707 and GSE69063, fat mass and obesity-associated protein (FTO) was identified as the sole gene exhibiting significant downregulation within the transcriptome of peripheral blood samples from sepsis patients among m6A-related proteins.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41235650"],"publication_contexts":[{"context_id":"disorder:Hospital-Acquired_Acute_Kidney_Injury","publication":"PMID:41235650"}],"publication":"PMID:41235650","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41235650","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Hospital-Acquired Acute Kidney Injury (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Hospital-Acquired_Acute_Kidney_Injury","name":"Hospital-Acquired Acute Kidney Injury","kind":"Disorder","source_path":"kb/disorders/Hospital-Acquired_Acute_Kidney_Injury.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hospital-Acquired_Acute_Kidney_Injury.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hospital-Acquired_Acute_Kidney_Injury.html#dataset-geo-gse297679"}],"context_names":["Hospital-Acquired Acute Kidney Injury"],"disease_names":["Hospital-Acquired Acute Kidney Injury"],"disease_name":"Hospital-Acquired Acute Kidney Injury","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hospital-Acquired_Acute_Kidney_Injury.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hospital-Acquired_Acute_Kidney_Injury.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hospital-Acquired_Acute_Kidney_Injury.html#dataset-geo-gse297679"]},{"id":"dataset:geo:gse297745","accession":"geo:GSE297745","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE297745","title":"IL-17A Neutralization Prevents Immune Checkpoint Inhibitor-Associated Myocarditis and Synergistically Enhances Immune Checkpoint Blockade Therapy","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["SPATIAL_TRANSCRIPTOMICS"],"data_type_labels":["Spatially resolved transcriptomics"],"data_type_label":"Spatially resolved transcriptomics","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"house mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[4],"sample_count":4,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Murine spatial transcriptomics of checkpoint-inhibitor myocarditis under IL-17A neutralization. Complements the IL-17 fibrosis evidence curated on the Post-Inflammatory Ventricular Remodeling node, from a different disease context."],"contexts":[{"id":"disorder:Myocarditis","name":"Myocarditis","kind":"Disorder","source_path":"kb/disorders/Myocarditis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myocarditis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Myocarditis.html#dataset-geo-gse297745"}],"context_names":["Myocarditis"],"disease_names":["Myocarditis"],"disease_name":"Myocarditis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Myocarditis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myocarditis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Myocarditis.html#dataset-geo-gse297745"]},{"id":"dataset:geo:gse297948","accession":"geo:GSE297948","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE297948","title":"Therapeutic Potential of ASO-Mediated KCNT1 Knockdown in KCNT1 Epileptic Encephalopathy","alternate_titles":[],"description":"Human transcriptomic profiling from the antisense-oligonucleotide knockdown programme that produced the first human KCNT1 treatment data. It is the molecular counterpart of the two-patient clinical report, and the only KCNT1-specific expression dataset in GEO.","alternate_descriptions":["KCNT1-related epileptic encephalopathy, including Epilepsy of Infancy with Migrating Focal Seizures (EIMFS), is a severe neurodevelopmental disorder associated with refractory seizures, profound neurologic impairment, and premature death. It is caused by de novo genetic variants in KCNT1 which alter the function of Slack, an evolutionarily conserved sodium-gated potassium channel that modulates neuronal firing patterns and excitability. Pathogenic KCNT1 variants lead to overactive Slack channels, boosting total neuronal potassium currents by up to 40%, driving cortical hyperexcitability and causing seizures."],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41981306"],"publication_contexts":[{"context_id":"disorder:Developmental_And_Epileptic_Encephalopathy_14","publication":"PMID:41981306"},{"context_id":"disorder:Epilepsy_of_Infancy_with_Migrating_Focal_Seizures","publication":"PMID:41981306"}],"publication":"PMID:41981306","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41981306","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located by searching GEO for the gene rather than the disease name. A disease-name search returns datasets for SCN8A, CDKL5, PNPLA8 and SCN1A developmental and epileptic encephalopathies, none of which are KCNT1; those were reviewed and rejected as Named Entity Confusion rather than curated here.","Identified by GEO DataSets index search for Epilepsy of Infancy with Migrating Focal Seizures (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Developmental_And_Epileptic_Encephalopathy_14","name":"Developmental and Epileptic Encephalopathy 14","kind":"Disorder","source_path":"kb/disorders/Developmental_And_Epileptic_Encephalopathy_14.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Developmental_And_Epileptic_Encephalopathy_14.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Developmental_and_Epileptic_Encephalopathy_14.html#dataset-geo-gse297948"},{"id":"disorder:Epilepsy_of_Infancy_with_Migrating_Focal_Seizures","name":"Epilepsy of Infancy with Migrating Focal Seizures","kind":"Disorder","source_path":"kb/disorders/Epilepsy_of_Infancy_with_Migrating_Focal_Seizures.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Epilepsy_of_Infancy_with_Migrating_Focal_Seizures.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Epilepsy_of_Infancy_with_Migrating_Focal_Seizures.html#dataset-geo-gse297948"}],"context_names":["Developmental and Epileptic Encephalopathy 14","Epilepsy of Infancy with Migrating Focal Seizures"],"disease_names":["Developmental and Epileptic Encephalopathy 14","Epilepsy of Infancy with Migrating Focal Seizures"],"disease_name":"Developmental and Epileptic Encephalopathy 14","same_context_model_ids":["model:kb/disorders/Developmental_And_Epileptic_Encephalopathy_14.yaml:KCNT1 P924L human iPSC-derived neurons","model:kb/disorders/Developmental_And_Epileptic_Encephalopathy_14.yaml:Xenopus oocyte two-electrode voltage clamp assay of mutant KCNT1"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Developmental_And_Epileptic_Encephalopathy_14.yaml","kb/disorders/Epilepsy_of_Infancy_with_Migrating_Focal_Seizures.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Developmental_And_Epileptic_Encephalopathy_14.yaml","https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Epilepsy_of_Infancy_with_Migrating_Focal_Seizures.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Developmental_and_Epileptic_Encephalopathy_14.html#dataset-geo-gse297948","https://dismech.monarchinitiative.org/pages/disorders/Epilepsy_of_Infancy_with_Migrating_Focal_Seizures.html#dataset-geo-gse297948"]},{"id":"dataset:geo:gse297954","accession":"geo:GSE297954","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE297954","title":"Recreating pathophysiology of CLN2 disease and demonstrating reversion by TPP1 gene therapy in hiPSCs-derived retinal organoid and retina-on-chip","alternate_titles":[],"description":"Mutations in tripeptidyl peptidase 1 (TPP1) gene lead to late infantile neuronal ceroid lipofuscinosis CLN2, characterized by lysosomal accumulation of lipofuscins predominantly found in brain and retina. The ocular phenotype is characterized by bilateral outer retinal degeneration that leads to complete vision loss. CLN2 animal models struggle in recapitulating the retinal phenotype observed in patients. Here, we leveraged human induced pluripotent stem cell (hiPSC)-derived retinal organoids (ROs), retinal pigmented epithelial (RPE) cells, and retina-on-chip (RoC) technologies to model CLN2 disease in vitro in patient-specific microphysiological models of the human retina.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[16],"sample_count":16,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40706588"],"publication_contexts":[{"context_id":"disorder:Neuronal_Ceroid_Lipofuscinosis","publication":"PMID:40706588"}],"publication":"PMID:40706588","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40706588","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Neuronal Ceroid Lipofuscinosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Neuronal_Ceroid_Lipofuscinosis","name":"Neuronal Ceroid Lipofuscinosis","kind":"Disorder","source_path":"kb/disorders/Neuronal_Ceroid_Lipofuscinosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Neuronal_Ceroid_Lipofuscinosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Neuronal_Ceroid_Lipofuscinosis.html#dataset-geo-gse297954"}],"context_names":["Neuronal Ceroid Lipofuscinosis"],"disease_names":["Neuronal Ceroid Lipofuscinosis"],"disease_name":"Neuronal Ceroid Lipofuscinosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Neuronal_Ceroid_Lipofuscinosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Neuronal_Ceroid_Lipofuscinosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Neuronal_Ceroid_Lipofuscinosis.html#dataset-geo-gse297954"]},{"id":"dataset:geo:gse29819","accession":"geo:GSE29819","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE29819","title":"Myocardial transcriptome analysis of human arrhythmogenic right ventricular cardiomyopathy (ARVC)","alternate_titles":[],"description":"Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy primarily of the right ventricle characterized through fibrofatty replacement of cardiomyocytes. The genetic etiology in ARVC patients is most commonly caused by dominant inheritance and high genetic heterogeneity. Though histological examinations of ARVC affected human myocardium reveals fibrolipomatous replacement, the molecular mechanisms leading to loss of cardiomyocytes are largely unknown.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[38],"sample_count":38,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:22085907"],"publication_contexts":[{"context_id":"disorder:Arrhythmogenic_Right_Ventricular_Cardiomyopathy","publication":"PMID:22085907"}],"publication":"PMID:22085907","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/22085907","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for arrhythmogenic right ventricular cardiomyopathy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Arrhythmogenic_Right_Ventricular_Cardiomyopathy","name":"arrhythmogenic right ventricular cardiomyopathy","kind":"Disorder","source_path":"kb/disorders/Arrhythmogenic_Right_Ventricular_Cardiomyopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Arrhythmogenic_Right_Ventricular_Cardiomyopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/arrhythmogenic_right_ventricular_cardiomyopathy.html#dataset-geo-gse29819"}],"context_names":["arrhythmogenic right ventricular cardiomyopathy"],"disease_names":["arrhythmogenic right ventricular cardiomyopathy"],"disease_name":"arrhythmogenic right ventricular cardiomyopathy","same_context_model_ids":["model:kb/disorders/Arrhythmogenic_Right_Ventricular_Cardiomyopathy.yaml:Heterozygous plakoglobin-deficient (plakoglobin+/-) mouse"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Arrhythmogenic_Right_Ventricular_Cardiomyopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Arrhythmogenic_Right_Ventricular_Cardiomyopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/arrhythmogenic_right_ventricular_cardiomyopathy.html#dataset-geo-gse29819"]},{"id":"dataset:geo:gse298216","accession":"geo:GSE298216","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE298216","title":"Verification of gene expression profiles in the liver tissues of mice after schistosomiasis infection","alternate_titles":[],"description":"In order to further improve our method for measuring gene expression after different days of schistosomiasis infection, we adopted whole-genome microarray expression analysis as the sequencing platform to identify those genes with potential for distinguishing different infection times (applicable for the corresponding exposure range of medical decisions in cases of schistosomiasis infection after different days). We infected 15-day, 24-day and 45-day healthy mice with schistosomiasis and determined a consensus characteristic of successful schistosomiasis infection, which could distinguish infection days and control samples.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[7],"sample_count":7,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Schistosomiasis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Schistosomiasis","name":"Schistosomiasis","kind":"Disorder","source_path":"kb/disorders/Schistosomiasis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Schistosomiasis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Schistosomiasis.html#dataset-geo-gse298216"}],"context_names":["Schistosomiasis"],"disease_names":["Schistosomiasis"],"disease_name":"Schistosomiasis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Schistosomiasis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Schistosomiasis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Schistosomiasis.html#dataset-geo-gse298216"]},{"id":"dataset:geo:gse298358","accession":"geo:GSE298358","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE298358","title":"Endothelins influences the proliferation-migration balance of IDH1-mutant glioma cells and promotes proneural to mesenchymal transition [RNAseq-Gb7-HUVEC]","alternate_titles":[],"description":"Adult diffuse gliomas are the deadliest brain tumours including IDH-wildtype glioblastomas of worst prognosis and diffuse low grade IDH-mutant astrocytomas and oligodendrogliomas. These glial tumours display distinct tumoral cell population defeating current therapies. Our group has unveiled the role of NOTCH signalling in glioblastoma cell plasticity and in the conversion of oligodendrocytic-like to astrocytic-like tumoral cells in IDH-mutant low-grade gliomas which escalate inevitably to higher grade malignant gliomas.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42026941"],"publication_contexts":[{"context_id":"disorder:Glioma","publication":"PMID:42026941"}],"publication":"PMID:42026941","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42026941","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Glioma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Glioma","name":"Glioma","kind":"Disorder","source_path":"kb/disorders/Glioma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Glioma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Glioma.html#dataset-geo-gse298358"}],"context_names":["Glioma"],"disease_names":["Glioma"],"disease_name":"Glioma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Glioma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Glioma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Glioma.html#dataset-geo-gse298358"]},{"id":"dataset:geo:gse298542","accession":"geo:GSE298542","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE298542","title":"Profiling and Functional Analysis of Urinary Exosomal MicroRNAs in Pregnant Women with Systemic Lupus Erythematosus","alternate_titles":[],"description":"Background: Pregnancy in Systemic Lupus Erythematosus (pSLE) is high-risk, necessitating non-invasive biomarkers for monitoring and predicting complications. Urinary exosomes, containing miRNAs, offer a promising source reflecting systemic and renal states, yet their profile in late gestation pSLE is less studied. Objective: This study aimed to investigate the profile of urinary exosomal miRNAs in pregnant women with SLE during late gestation compared to healthy pregnant controls and to explore their potential biological roles and pathways. Methods: Urinary exosomes were isolated from 6 pSLE patients and 5 controls. Exosomes were characterized, and miRNAs were sequenced.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[11],"sample_count":11,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Systemic Lupus Erythematosus (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Systemic_Lupus_Erythematosus","name":"Systemic Lupus Erythematosus","kind":"Disorder","source_path":"kb/disorders/Systemic_Lupus_Erythematosus.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Systemic_Lupus_Erythematosus.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Systemic_Lupus_Erythematosus.html#dataset-geo-gse298542"}],"context_names":["Systemic Lupus Erythematosus"],"disease_names":["Systemic Lupus Erythematosus"],"disease_name":"Systemic Lupus Erythematosus","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Systemic_Lupus_Erythematosus.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Systemic_Lupus_Erythematosus.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Systemic_Lupus_Erythematosus.html#dataset-geo-gse298542"]},{"id":"dataset:geo:gse298694","accession":"geo:GSE298694","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE298694","title":"Differential RNA splicing analysis with or without IL-6 in multiple myeloma cells","alternate_titles":[],"description":"Multiple myeloma (MM) is a plasma cell neoplasm that depends on the bone marrow (BM) microenvironment; however, the underlying mechanisms of epigenetic contribution to the pathogenesis of MM are incompletely understood. Here, we delineate the epigenetic-driven transcriptional and splicing program crucial for MM. We recharacterized transcriptional program induced by IL-6/JAK/STAT3 pathway by ChIP-seq and RNA-seq analyses combined with CRIPSR knockout screening database, and identified B cell lineage factors, POU2AF1 and ELL2, as crucial IL-6/JAK/STAT3 targets that are essential for MM cell growth and survival.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[42],"sample_count":42,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41925579"],"publication_contexts":[{"context_id":"disorder:Plasma_Cell_Neoplasm","publication":"PMID:41925579"}],"publication":"PMID:41925579","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41925579","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Plasma Cell Neoplasm (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Plasma_Cell_Neoplasm","name":"Plasma Cell Neoplasm","kind":"Disorder","source_path":"kb/disorders/Plasma_Cell_Neoplasm.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Plasma_Cell_Neoplasm.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Plasma_Cell_Neoplasm.html#dataset-geo-gse298694"}],"context_names":["Plasma Cell Neoplasm"],"disease_names":["Plasma Cell Neoplasm"],"disease_name":"Plasma Cell Neoplasm","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Plasma_Cell_Neoplasm.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Plasma_Cell_Neoplasm.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Plasma_Cell_Neoplasm.html#dataset-geo-gse298694"]},{"id":"dataset:geo:gse298742","accession":"geo:GSE298742","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE298742","title":"Hand1 gene replacement with Hand2 reveals overlap in function with unique occurrence of omphalocele and heart defects [Spatial Transcriptomics]","alternate_titles":[],"description":"The bHLH transcription factors HAND1 and HAND2 are expressed in partially overlapping patterns during development. Studies have established evidence for significant functional redundancy between HAND1 and HAND2. To test redundancy fully, we engineered a Hand1 allele where we directly replace the exons and intron with those of Hand2. Results show that 2% of Hand1Hand2/ Hand2 mice are viable, and fertile. The remaining Hand1Hand2/Hand2 embryos exhibit neonatal lethality due to omphalocele, ventricular septal defects and conduction anomalies.","alternate_descriptions":[],"data_types":["SPATIAL_TRANSCRIPTOMICS"],"data_type_labels":["Spatially resolved transcriptomics"],"data_type_label":"Spatially resolved transcriptomics","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[15],"sample_count":15,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Omphalocele (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Omphalocele","name":"Omphalocele","kind":"Disorder","source_path":"kb/disorders/Omphalocele.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Omphalocele.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Omphalocele.html#dataset-geo-gse298742"}],"context_names":["Omphalocele"],"disease_names":["Omphalocele"],"disease_name":"Omphalocele","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Omphalocele.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Omphalocele.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Omphalocele.html#dataset-geo-gse298742"]},{"id":"dataset:geo:gse298801","accession":"geo:GSE298801","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE298801","title":"Cardiomyocyte-specific Deletion of Med13 and Med13L Results in Dysregulated Gene Expression and Lethal Heart Failure","alternate_titles":[],"description":"Bulk RNA-seq from adult murine cardiomyocytes after inducible knockout of Med13 and Med13L. Included on the MED13L entry because it is the primary evidence for MED13/MED13L functional redundancy, which underpins the paralog-compensation hypothesis for MED13L's variable cardiac penetrance.","alternate_descriptions":["Bulk RNA-seq from adult murine cardiomyocytes after inducible knockout of Med13 and Med13L. Double knockout results in lethal heart failure within 6 weeks, with significant gene dysregulation of fibrotic pathways and calcium handling. Demonstrates that Med13 and Med13L function redundantly in the adult heart to maintain basal cardiac function and transcription, relevant to the congenital heart defects observed in MED13 syndrome.","Bulk RNA-seq from adult murine cardiomyocytes after inducible knockout of Med13 and Med13L. Double knockout results in lethal heart failure within 6 weeks, with significant gene dysregulation of fibrotic pathways and calcium handling. Demonstrates that Med13 and Med13L function redundantly in the adult heart to maintain basal cardiac function and transcription."],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[{"id":"UBERON:0000948","label":"heart","display_label":"heart","url":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"CL:0000746","label":"cardiac muscle cell","display_label":"cardiomyocyte","url":"http://purl.obolibrary.org/obo/CL_0000746"}],"sample_type_labels":["heart","cardiac muscle cell"],"sample_counts":[8],"sample_count":8,"conditions":["Med13/Med13L cardiomyocyte-specific double knockout","wild-type control"],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:22474","label":"MED13","display_label":"MED13","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/22474"},{"id":"hgnc:22962","label":"MED13L","display_label":"MED13L","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/22962"}],"genes":["MED13","MED13L"],"platforms":[],"platform":null,"publications":["PMID:40989238"],"publication_contexts":[{"context_id":"disorder:MED13L_Syndrome","publication":"PMID:40989238"},{"context_id":"disorder:MED13_Syndrome","publication":"PMID:40989238"},{"context_id":"disorder:Mediator_Complex_Neurodevelopmental_Disorder","publication":"PMID:40989238"}],"publication":"PMID:40989238","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40989238","publication_status":"Publication recorded","findings":[{"statement":"Med13 and Med13L are functionally redundant in adult cardiomyocytes","evidence":[]},{"statement":"Combined knockout causes lethal heart failure with fibrotic and calcium-handling gene dysregulation","evidence":[]},{"statement":"Med13 and Med13L are functionally redundant in adult cardiomyocytes","evidence":[]},{"statement":"Double knockout causes lethal heart failure with fibrotic and calcium handling gene dysregulation","evidence":[]},{"statement":"Similar gene dysregulation patterns across Mediator cardiac knockouts (Med13/13L, Med12, Med1, Med30)","evidence":[]},{"statement":"Med13 and Med13L are functionally redundant in adult cardiomyocytes","evidence":[]},{"statement":"Double knockout causes lethal heart failure with fibrotic and calcium handling gene dysregulation","evidence":[]},{"statement":"Similar gene dysregulation patterns across Mediator cardiac knockouts (Med13/13L, Med12, Med1, Med30)","evidence":[]}],"findings_text":["Med13 and Med13L are functionally redundant in adult cardiomyocytes","Combined knockout causes lethal heart failure with fibrotic and calcium-handling gene dysregulation","Double knockout causes lethal heart failure with fibrotic and calcium handling gene dysregulation","Similar gene dysregulation patterns across Mediator cardiac knockouts (Med13/13L, Med12, Med1, Med30)"],"evidence":[{"reference":"PMID:40989238","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40989238","reference_title":"Med13 and Med13L: Critical redundant players in basal cardiac function and gene expression.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"Med13/13L knockout resulted in decreased cardiac function leading to lethal heart failure in a median timeframe of 6 weeks from the start of tamoxifen.","explanation":"Establishes the redundancy result that this dataset supports and that the paralog-compensation hypothesis rests on."}],"notes":[],"contexts":[{"id":"disorder:MED13L_Syndrome","name":"MED13L Syndrome","kind":"Disorder","source_path":"kb/disorders/MED13L_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MED13L_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/MED13L_Syndrome.html#dataset-geo-gse298801"},{"id":"disorder:MED13_Syndrome","name":"MED13 Syndrome","kind":"Disorder","source_path":"kb/disorders/MED13_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MED13_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/MED13_Syndrome.html#dataset-geo-gse298801"},{"id":"disorder:Mediator_Complex_Neurodevelopmental_Disorder","name":"Mediator Complex Neurodevelopmental Disorder","kind":"Disorder","source_path":"kb/disorders/Mediator_Complex_Neurodevelopmental_Disorder.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mediator_Complex_Neurodevelopmental_Disorder.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Mediator_Complex_Neurodevelopmental_Disorder.html#dataset-geo-gse298801"}],"context_names":["MED13L Syndrome","MED13 Syndrome","Mediator Complex Neurodevelopmental Disorder"],"disease_names":["MED13L Syndrome","MED13 Syndrome","Mediator Complex Neurodevelopmental Disorder"],"disease_name":"MED13L Syndrome","same_context_model_ids":["model:kb/disorders/MED13L_Syndrome.yaml:In utero electroporation of mouse cortex with MED13L variants","model:kb/disorders/MED13L_Syndrome.yaml:iPSC-derived neural progenitor CRISPRi Perturb-seq platform","model:kb/disorders/MED13L_Syndrome.yaml:MED13L patient-derived skin fibroblasts"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/MED13L_Syndrome.yaml","kb/disorders/MED13_Syndrome.yaml","kb/disorders/Mediator_Complex_Neurodevelopmental_Disorder.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MED13L_Syndrome.yaml","https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MED13_Syndrome.yaml","https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mediator_Complex_Neurodevelopmental_Disorder.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/MED13L_Syndrome.html#dataset-geo-gse298801","https://dismech.monarchinitiative.org/pages/disorders/MED13_Syndrome.html#dataset-geo-gse298801","https://dismech.monarchinitiative.org/pages/disorders/Mediator_Complex_Neurodevelopmental_Disorder.html#dataset-geo-gse298801"]},{"id":"dataset:geo:gse298871","accession":"geo:GSE298871","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE298871","title":"Transcriptomic profiling of vitiligo patients shows polar immune dysregulation in involved and uninvolved skin","alternate_titles":[],"description":"Background: Vitiligo is a chronic autoimmune skin depigmenting disorder, with a major impact on quality of life. Therapeutic options are still limited, with only one topical JAK inhibitor being FDA-approved. Although vitiligo is primarily regarded as a Th1/IFN-driven disease, emerging evidence suggests the involvement of additional immune axes, but their relevance to disease pathogenesis remains unclear. Objective: To obtain a global cutaneous transcriptomic profile of lesional and nonlesional vitiligo. Results: Robust inflammatory dysregulation was captured not only in lesional, but also nonlesional vitiligo skin relative to healthy controls.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[17],"sample_count":17,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40513622"],"publication_contexts":[{"context_id":"disorder:Vitiligo","publication":"PMID:40513622"}],"publication":"PMID:40513622","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40513622","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Vitiligo (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Vitiligo","name":"Vitiligo","kind":"Disorder","source_path":"kb/disorders/Vitiligo.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Vitiligo.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Vitiligo.html#dataset-geo-gse298871"}],"context_names":["Vitiligo"],"disease_names":["Vitiligo"],"disease_name":"Vitiligo","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Vitiligo.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Vitiligo.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Vitiligo.html#dataset-geo-gse298871"]},{"id":"dataset:geo:gse299162","accession":"geo:GSE299162","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE299162","title":"AAV-mediated ARSA replacement for the treatment of Metachromatic Leukodystrophy","alternate_titles":[],"description":"Metachromatic leukodystrophy (MLD) is an autosomal recessive neurodegenerative disorder caused by mutations in the arylsulfatase A (ARSA) gene, resulting in lower sulfatase activity and the toxic accumulation of sulfatides in the central and peripheral nervous system. Children account for 70% of cases and become progressively disabled with death occurring within 10 years of disease onset. Gene therapy approaches to restore ARSA expression via adeno- associated viral vectors (AAV) have been promising but hampered by limited brain biodistribution.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[8],"sample_count":8,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40536808"],"publication_contexts":[{"context_id":"disorder:Metachromatic_Leukodystrophy","publication":"PMID:40536808"}],"publication":"PMID:40536808","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40536808","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Metachromatic Leukodystrophy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Metachromatic_Leukodystrophy","name":"Metachromatic Leukodystrophy","kind":"Disorder","source_path":"kb/disorders/Metachromatic_Leukodystrophy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Metachromatic_Leukodystrophy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Metachromatic_Leukodystrophy.html#dataset-geo-gse299162"}],"context_names":["Metachromatic Leukodystrophy"],"disease_names":["Metachromatic Leukodystrophy"],"disease_name":"Metachromatic Leukodystrophy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Metachromatic_Leukodystrophy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Metachromatic_Leukodystrophy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Metachromatic_Leukodystrophy.html#dataset-geo-gse299162"]},{"id":"dataset:geo:gse299253","accession":"geo:GSE299253","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE299253","title":"Hand1 gene replacement with Hand2 reveals overlap in function with unique occurrence of omphalocele and heart defects [scRNA-seq]","alternate_titles":[],"description":"The bHLH transcription factors HAND1 and HAND2 are expressed in partially overlapping patterns during development. Studies have established evidence for significant functional redundancy between HAND1 and HAND2. To test redundancy fully, we engineered a Hand1 allele where we directly replace the exons and intron with those of Hand2. Results show that 2% of Hand1Hand2/ Hand2 mice are viable, and fertile. The remaining Hand1Hand2/Hand2 embryos exhibit neonatal lethality due to omphalocele, ventricular septal defects and conduction anomalies.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[9],"sample_count":9,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40960281"],"publication_contexts":[{"context_id":"disorder:Omphalocele","publication":"PMID:40960281"}],"publication":"PMID:40960281","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40960281","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Omphalocele (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Omphalocele","name":"Omphalocele","kind":"Disorder","source_path":"kb/disorders/Omphalocele.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Omphalocele.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Omphalocele.html#dataset-geo-gse299253"}],"context_names":["Omphalocele"],"disease_names":["Omphalocele"],"disease_name":"Omphalocele","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Omphalocele.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Omphalocele.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Omphalocele.html#dataset-geo-gse299253"]},{"id":"dataset:geo:gse299579","accession":"geo:GSE299579","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE299579","title":"Hand1 gene replacement with Hand2 reveals overlap in function with unique occurrence of omphalocele and heart defects","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[24],"sample_count":24,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Omphalocele (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Omphalocele","name":"Omphalocele","kind":"Disorder","source_path":"kb/disorders/Omphalocele.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Omphalocele.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Omphalocele.html#dataset-geo-gse299579"}],"context_names":["Omphalocele"],"disease_names":["Omphalocele"],"disease_name":"Omphalocele","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Omphalocele.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Omphalocele.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Omphalocele.html#dataset-geo-gse299579"]},{"id":"dataset:geo:gse299582","accession":"geo:GSE299582","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE299582","title":"Transcriptome analysis of circulating microRNAs associated with Chagas disease susceptibility and chronic Chagas cardiomyopathy severity","alternate_titles":[],"description":"Chagas disease (CD), caused by infection with the protozoan parasite Trypanosoma cruzi, is a major public health concern in Latin America. Understanding the molecular mechanisms driving disease progression and identifying biomarkers are crucial. We investigated the association of circulating microRNAs (miRNAs) with CD susceptibility and heart disease progression. A multicentric prospective observational study was conducted with 150 CD patients (46 indeterminate, 104 CCC [chronic chagasic cardiomyopathy] staged A-D) and 42 healthy controls from CD endemic areas. Sequencing of circulating miRNAs was performed, and differential expression analyses were conducted.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[192],"sample_count":192,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41574750"],"publication_contexts":[{"context_id":"disorder:Chagas_Disease","publication":"PMID:41574750"}],"publication":"PMID:41574750","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41574750","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Chagas disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Chagas_Disease","name":"Chagas disease","kind":"Disorder","source_path":"kb/disorders/Chagas_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chagas_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chagas_disease.html#dataset-geo-gse299582"}],"context_names":["Chagas disease"],"disease_names":["Chagas disease"],"disease_name":"Chagas disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chagas_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chagas_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chagas_disease.html#dataset-geo-gse299582"]},{"id":"dataset:geo:gse299693","accession":"geo:GSE299693","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE299693","title":"A Genome-Wide CRISPR Screen Identifies DTX4 Modulating Alveolar Macrophage Cholesterol Efflux in Pulmonary Alveolar Proteinosis [RNA-seq II]","alternate_titles":[],"description":"Pulmonary alveolar proteinosis (PAP) is a rare pulmonary syndrome characterized by impaired surfactant clearance, driven by dysfunctional cholesterol efflux in alveolar macrophages (AMs). However, the molecular determinants governing AM cholesterol homeostasis remain largely elusive. Here, through a genome-wide CRISPR activation screen in foamy macrophages and bulk RNA sequencing of AMs from PAP patients, we identify Deltex E3 Ubiquitin Ligase 4 (DTX4) as a pivotal regulator of cholesterol efflux in AMs.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Hereditary Pulmonary Alveolar Proteinosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Hereditary_Pulmonary_Alveolar_Proteinosis","name":"Hereditary Pulmonary Alveolar Proteinosis","kind":"Disorder","source_path":"kb/disorders/Hereditary_Pulmonary_Alveolar_Proteinosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hereditary_Pulmonary_Alveolar_Proteinosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hereditary_Pulmonary_Alveolar_Proteinosis.html#dataset-geo-gse299693"}],"context_names":["Hereditary Pulmonary Alveolar Proteinosis"],"disease_names":["Hereditary Pulmonary Alveolar Proteinosis"],"disease_name":"Hereditary Pulmonary Alveolar Proteinosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hereditary_Pulmonary_Alveolar_Proteinosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hereditary_Pulmonary_Alveolar_Proteinosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hereditary_Pulmonary_Alveolar_Proteinosis.html#dataset-geo-gse299693"]},{"id":"dataset:geo:gse299696","accession":"geo:GSE299696","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE299696","title":"A Genome-Wide CRISPR Screen Identifies DTX4 Modulating Alveolar Macrophage Cholesterol Efflux in Pulmonary Alveolar Proteinosis [CRISPR]","alternate_titles":[],"description":"Pulmonary alveolar proteinosis (PAP) is a rare pulmonary syndrome characterized by impaired surfactant clearance, driven by dysfunctional cholesterol efflux in alveolar macrophages (AMs). However, the molecular determinants governing AM cholesterol homeostasis remain largely elusive. Here, through a genome-wide CRISPR activation screen in foamy macrophages and bulk RNA sequencing of AMs from PAP patients, we identify Deltex E3 Ubiquitin Ligase 4 (DTX4) as a pivotal regulator of cholesterol efflux in AMs.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Hereditary Pulmonary Alveolar Proteinosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Hereditary_Pulmonary_Alveolar_Proteinosis","name":"Hereditary Pulmonary Alveolar Proteinosis","kind":"Disorder","source_path":"kb/disorders/Hereditary_Pulmonary_Alveolar_Proteinosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hereditary_Pulmonary_Alveolar_Proteinosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hereditary_Pulmonary_Alveolar_Proteinosis.html#dataset-geo-gse299696"}],"context_names":["Hereditary Pulmonary Alveolar Proteinosis"],"disease_names":["Hereditary Pulmonary Alveolar Proteinosis"],"disease_name":"Hereditary Pulmonary Alveolar Proteinosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hereditary_Pulmonary_Alveolar_Proteinosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hereditary_Pulmonary_Alveolar_Proteinosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hereditary_Pulmonary_Alveolar_Proteinosis.html#dataset-geo-gse299696"]},{"id":"dataset:geo:gse299706","accession":"geo:GSE299706","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE299706","title":"Transcriptome regulation in T-cells and monocytes in patients with Common Variable Immunodeficiency","alternate_titles":[],"description":"A large subgroup of Common Variable Immunodeficiency (CVID) patients has autoimmune and inflammatory complications, associated with T cell and monocyte pathology, but the molecular mechanism for this CVID-subgroup is still elusive. To identify novel molecular pathways impacted in CVID T cells and monocytes, we examined the transcriptomic profiles in these cells from healthy control and the CVID patients in the subgroup with inflammatory complications.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[20],"sample_count":20,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41991796"],"publication_contexts":[{"context_id":"disorder:Common_Variable_Immunodeficiency","publication":"PMID:41991796"}],"publication":"PMID:41991796","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41991796","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Common Variable Immunodeficiency (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Common_Variable_Immunodeficiency","name":"Common Variable Immunodeficiency","kind":"Disorder","source_path":"kb/disorders/Common_Variable_Immunodeficiency.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Common_Variable_Immunodeficiency.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Common_Variable_Immunodeficiency.html#dataset-geo-gse299706"}],"context_names":["Common Variable Immunodeficiency"],"disease_names":["Common Variable Immunodeficiency"],"disease_name":"Common Variable Immunodeficiency","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Common_Variable_Immunodeficiency.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Common_Variable_Immunodeficiency.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Common_Variable_Immunodeficiency.html#dataset-geo-gse299706"]},{"id":"dataset:geo:gse299759","accession":"geo:GSE299759","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE299759","title":"An integrated clinical genomic and transcriptomic subgrouping of central chondrosarcoma","alternate_titles":[],"description":"Chondrosarcoma, a malignant cartilage-producing bone tumor, is the second most-common bone sarcoma. Chondrosarcomas are histologically graded, which is so far the best predictor of survival. Early mutations in isocitrate dehydrogenase (IDH)-1 and -2 genes are frequent, leading to the production of the oncometabolite D-2-hydroxyglutarate, which affects DNA methylation, resulting in a preferred chondrogenic differentiation over osteogenic differentiation of mesenchymal stem cells, which are currently considered the precursor cells of chondrosarcomas.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[54],"sample_count":54,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40976495"],"publication_contexts":[{"context_id":"disorder:Chondrosarcoma","publication":"PMID:40976495"}],"publication":"PMID:40976495","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40976495","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Chondrosarcoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Chondrosarcoma","name":"Chondrosarcoma","kind":"Disorder","source_path":"kb/disorders/Chondrosarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chondrosarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chondrosarcoma.html#dataset-geo-gse299759"}],"context_names":["Chondrosarcoma"],"disease_names":["Chondrosarcoma"],"disease_name":"Chondrosarcoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chondrosarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chondrosarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chondrosarcoma.html#dataset-geo-gse299759"]},{"id":"dataset:geo:gse299877","accession":"geo:GSE299877","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE299877","title":"N-acetyl-L-cysteine ethyl ester (NACET) induces the transcription factor NRF2 in the retina and prevents its aging and diabetic retinopathy. [III]","alternate_titles":[],"description":"Age-related macular degeneration (AMD) and diabetic retinopathy (DR) are leading causes of visual impairment in older people, with oxidative stress playing a central role in the development of these diseases. In fact, the cells of the retina are particularly susceptible to oxidative damage due to high metabolic activity and exposure to light. Glutathione (GSH), a key intracellular antioxidant, is essential for retinal protection but it becomes limited during aging and in diabetes patients.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[20],"sample_count":20,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41205411"],"publication_contexts":[{"context_id":"disorder:Diabetic_Retinopathy","publication":"PMID:41205411"}],"publication":"PMID:41205411","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41205411","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Diabetic Retinopathy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Diabetic_Retinopathy","name":"Diabetic Retinopathy","kind":"Disorder","source_path":"kb/disorders/Diabetic_Retinopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Diabetic_Retinopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Diabetic_Retinopathy.html#dataset-geo-gse299877"}],"context_names":["Diabetic Retinopathy"],"disease_names":["Diabetic Retinopathy"],"disease_name":"Diabetic Retinopathy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Diabetic_Retinopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Diabetic_Retinopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Diabetic_Retinopathy.html#dataset-geo-gse299877"]},{"id":"dataset:geo:gse299937","accession":"geo:GSE299937","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE299937","title":"Srrm2 haploinsufficiency drives SynGAP-gamma reduction, Agap3 mis-splicing, and oligodendrocyte deficits in a genetic mouse model of schizophrenia","alternate_titles":[],"description":"Two arms comparing Srrm2+/- mice with wild-type littermates: bulk RNA-seq of eight brain regions at 1 and 3 months, plus single-NUCLEUS RNA-seq of prefrontal cortex and striatum at 1 month. This is the haploinsufficiency model underlying the Impaired Neuronal and Oligodendrocyte Development node, and the source data for the reduced striatal oligodendrocyte proportion and the myelin-gene expression changes.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"Mus musculus","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[180],"sample_count":180,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:16639","label":"SRRM2","display_label":"SRRM2","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/16639"}],"genes":["SRRM2"],"platforms":[],"platform":null,"publications":["PMID:42189682"],"publication_contexts":[{"context_id":"disorder:Intellectual_Developmental_Disorder_Autosomal_Dominant_72","publication":"PMID:42189682"}],"publication":"PMID:42189682","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42189682","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Relevance triage: matched on gene rather than disease name, but the linked publication is the Srrm2+/- brain model curated in animal_models here, so the dataset is directly on-target for this entry's mechanism. data_type records the larger bulk RNA-seq arm; the record also contains a single-nucleus RNA-seq arm, which the single-valued slot cannot express. Bulk-generated record - carries publication and provenance notes rather than an evidence block, per the dataset-curation SOP."],"contexts":[{"id":"disorder:Intellectual_Developmental_Disorder_Autosomal_Dominant_72","name":"Intellectual Developmental Disorder, Autosomal Dominant 72","kind":"Disorder","source_path":"kb/disorders/Intellectual_Developmental_Disorder_Autosomal_Dominant_72.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Intellectual_Developmental_Disorder_Autosomal_Dominant_72.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Intellectual_Developmental_Disorder,_Autosomal_Dominant_72.html#dataset-geo-gse299937"}],"context_names":["Intellectual Developmental Disorder, Autosomal Dominant 72"],"disease_names":["Intellectual Developmental Disorder, Autosomal Dominant 72"],"disease_name":"Intellectual Developmental Disorder, Autosomal Dominant 72","same_context_model_ids":["model:kb/disorders/Intellectual_Developmental_Disorder_Autosomal_Dominant_72.yaml:Srrm2 heterozygous mouse embryonic stem cells","model:kb/disorders/Intellectual_Developmental_Disorder_Autosomal_Dominant_72.yaml:SRRM2-deficient human iPSC-derived neurons"],"candidate_model_ids":["model:kb/disorders/Intellectual_Developmental_Disorder_Autosomal_Dominant_72.yaml:SRRM2-deficient human iPSC-derived neurons"],"association_basis":"Same publication as a NAM (candidate)","nam_disease_context":"Same publication as a NAM (candidate)","source_paths":["kb/disorders/Intellectual_Developmental_Disorder_Autosomal_Dominant_72.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Intellectual_Developmental_Disorder_Autosomal_Dominant_72.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Intellectual_Developmental_Disorder,_Autosomal_Dominant_72.html#dataset-geo-gse299937"]},{"id":"dataset:geo:gse299979","accession":"geo:GSE299979","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE299979","title":"A Novel LMX1A Frameshift Variant Underlies Familial Phenotypic Heterogeneity in DFNA7","alternate_titles":[],"description":"RNA sequencing of HEI-OC1 cells expressing wild-type or c.405delT Lmx1a. The paper presents three biological replicates per group.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:6653","label":"LMX1A","display_label":"LMX1A","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/6653"}],"genes":["LMX1A"],"platforms":[],"platform":null,"publications":["PMID:42253511"],"publication_contexts":[{"context_id":"disorder:Autosomal_Dominant_Nonsyndromic_Hearing_Loss_7","publication":"PMID:42253511"}],"publication":"PMID:42253511","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42253511","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE299979","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE299979","reference_title":"A Novel LMX1A Frameshift Variant Underlies Familial Phenotypic Heterogeneity in DFNA7","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"RNA sequencing (RNA-seq) of HEI-OC1 cells","explanation":"Generated GEO record confirms the system and assay; the primary paper supplies the experimental interpretation."}],"notes":["Exploratory overexpression comparison; the GEO summary emphasizes neurodevelopmental/synaptic/mitochondrial pathways, whereas the final paper also emphasizes immune and ER-stress enrichment. Neither summary is patient-tissue evidence. No proteomics accession is asserted."],"contexts":[{"id":"disorder:Autosomal_Dominant_Nonsyndromic_Hearing_Loss_7","name":"Autosomal Dominant Nonsyndromic Hearing Loss 7","kind":"Disorder","source_path":"kb/disorders/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_7.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_7.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_7.html#dataset-geo-gse299979"}],"context_names":["Autosomal Dominant Nonsyndromic Hearing Loss 7"],"disease_names":["Autosomal Dominant Nonsyndromic Hearing Loss 7"],"disease_name":"Autosomal Dominant Nonsyndromic Hearing Loss 7","same_context_model_ids":["model:kb/disorders/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_7.yaml:HEI-OC1 Lmx1a overexpression and RNA-decay model","model:kb/disorders/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_7.yaml:HEK293 LMX1A transactivation reporter"],"candidate_model_ids":["model:kb/disorders/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_7.yaml:HEI-OC1 Lmx1a overexpression and RNA-decay model","model:kb/disorders/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_7.yaml:HEK293 LMX1A transactivation reporter"],"association_basis":"Same publication as a NAM (candidate)","nam_disease_context":"Same publication as a NAM (candidate)","source_paths":["kb/disorders/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_7.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_7.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_7.html#dataset-geo-gse299979"]},{"id":"dataset:geo:gse300286","accession":"geo:GSE300286","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE300286","title":"FOXP1 and FOXP4 function in mouse regulatory T cells [RNA-seq]","alternate_titles":[],"description":"Bulk RNA sequencing of sorted splenic regulatory T cells from conditional Foxp1/Foxp4 mutant and control mice. This is an indirect model of reduced CD25 expression and altered Treg function, not a patient IL2RA-deficiency dataset.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"Mus musculus","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40794436"],"publication_contexts":[{"context_id":"disorder:CD25_Deficiency","publication":"PMID:40794436"}],"publication":"PMID:40794436","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40794436","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:40794436","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/40794436","reference_title":"Normal Treg homeostasis and suppressive function require both FOXP1 and FOXP4.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"We further show that FOXP1 and FOXP4 bind to Il2ra promoter regions to regulate CD25 expression in Tregs.","explanation":"The source establishes the relevance of this indirect regulatory model."}],"notes":["Foxp1/Foxp4 deletion affects many Treg programs; its transcriptome cannot be attributed solely to IL2RA. See the corresponding animal model for preserved in-vitro suppression and impaired in-vivo suppression."],"contexts":[{"id":"disorder:CD25_Deficiency","name":"CD25 Deficiency","kind":"Disorder","source_path":"kb/disorders/CD25_Deficiency.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/CD25_Deficiency.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/CD25_Deficiency.html#dataset-geo-gse300286"}],"context_names":["CD25 Deficiency"],"disease_names":["CD25 Deficiency"],"disease_name":"CD25 Deficiency","same_context_model_ids":["model:kb/disorders/CD25_Deficiency.yaml:Founding-patient EBV-transformed B cells","model:kb/disorders/CD25_Deficiency.yaml:GMP-compatible gene-corrected autologous Treg product","model:kb/disorders/CD25_Deficiency.yaml:Nonviral gene-corrected IL2RA-deficient T cells","model:kb/disorders/CD25_Deficiency.yaml:S166N patient PBMC and T-cell cultures","model:kb/disorders/CD25_Deficiency.yaml:Y41S patient NK-cell functional cultures"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/CD25_Deficiency.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/CD25_Deficiency.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/CD25_Deficiency.html#dataset-geo-gse300286"]},{"id":"dataset:geo:gse300303","accession":"geo:GSE300303","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE300303","title":"Chikungunya virus persists in joint associated macrophages and promotes chronic disease [Xenium]","alternate_titles":[],"description":"Arthritogenic alphaviruses, including chikungunya virus (CHIKV), Mayaro virus and Ross River virus, cause long-lasting musculoskeletal pain and inflammation. However, the mechanisms driving chronic disease remain unclear. Here, we used single-cell RNA sequencing, spatial transcriptomics and flow cytometry to investigate joint-associated tissues in alphavirus-infected mice at a late stage of infection. We identified an accumulation of inflammatory macrophages in joint-associated tissues with elevated expression of inflammatory markers. These cells harbour CHIKV RNA, suggesting ongoing viral replication during chronic disease.","alternate_descriptions":[],"data_types":["SPATIAL_TRANSCRIPTOMICS"],"data_type_labels":["Spatially resolved transcriptomics"],"data_type_label":"Spatially resolved transcriptomics","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41922840"],"publication_contexts":[{"context_id":"disorder:Chikungunya","publication":"PMID:41922840"}],"publication":"PMID:41922840","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41922840","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Chikungunya (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Chikungunya","name":"Chikungunya","kind":"Disorder","source_path":"kb/disorders/Chikungunya.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chikungunya.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chikungunya.html#dataset-geo-gse300303"}],"context_names":["Chikungunya"],"disease_names":["Chikungunya"],"disease_name":"Chikungunya","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chikungunya.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chikungunya.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chikungunya.html#dataset-geo-gse300303"]},{"id":"dataset:geo:gse300490","accession":"geo:GSE300490","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE300490","title":"Defining the Ovarian Cancer Precancerous Landscape through Modeling Fallopian Tube Epithelium Reprogramming Driven by Extracellular Vesicles","alternate_titles":[],"description":"Serous tubal intraepithelial carcinomas (STIC lesions) in the human fallopian tube epithelium (hFTE) are theorized to give rise to high grade serous ovarian cancers (HGSOC). Small extracellular vesicles (sEVs) are known to mediate key signaling in both normal and cancerous tissues, but few ex vivo systems exist for studying sEV impact on hFTE tissue. Here, we present a microfluidic tissue culture platform with combined spatial transcriptomic and proteomic readouts that allows us to profile dual responses in tissue exposed to sEV “messages”—capturing both short-term transcriptomic shifts in the tissue and long-term changes in protein cargo of secreted EVs (the “reply”).","alternate_descriptions":[],"data_types":["SPATIAL_TRANSCRIPTOMICS"],"data_type_labels":["Spatially resolved transcriptomics"],"data_type_label":"Spatially resolved transcriptomics","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[624],"sample_count":624,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40689422"],"publication_contexts":[{"context_id":"disorder:Fallopian_Tube_Cancer","publication":"PMID:40689422"}],"publication":"PMID:40689422","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40689422","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Fallopian Tube Cancer (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Fallopian_Tube_Cancer","name":"Fallopian Tube Cancer","kind":"Disorder","source_path":"kb/disorders/Fallopian_Tube_Cancer.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fallopian_Tube_Cancer.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Fallopian_Tube_Cancer.html#dataset-geo-gse300490"}],"context_names":["Fallopian Tube Cancer"],"disease_names":["Fallopian Tube Cancer"],"disease_name":"Fallopian Tube Cancer","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Fallopian_Tube_Cancer.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fallopian_Tube_Cancer.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Fallopian_Tube_Cancer.html#dataset-geo-gse300490"]},{"id":"dataset:geo:gse301005","accession":"geo:GSE301005","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE301005","title":"Modeling arrhythmogenic cardiomyopathy fattyfibro pathology through the use of PKP2-deficient human iPSC-derived epicardial cells","alternate_titles":[],"description":"Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiac disease characterized by progressive fatty-fibro replacement of the ventricular myocardium leading to arrhythmias and an increased risk of sudden cardiac death. To date, the cell types and signaling mechanisms involved in fatty-fibro infiltration of the myocardium have yet to be fully resolved. However, given that fatty-fibro replacement is initiated within the subepicardial layer, epicardial cells are predicted to contribute to the development of this pathology.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[17],"sample_count":17,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41145823"],"publication_contexts":[{"context_id":"disorder:PKP2_Cardiomyopathy","publication":"PMID:41145823"}],"publication":"PMID:41145823","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41145823","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for PKP2 Cardiomyopathy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:PKP2_Cardiomyopathy","name":"PKP2_Cardiomyopathy","kind":"Disorder","source_path":"kb/disorders/PKP2_Cardiomyopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/PKP2_Cardiomyopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/PKP2_Cardiomyopathy.html#dataset-geo-gse301005"}],"context_names":["PKP2_Cardiomyopathy"],"disease_names":["PKP2_Cardiomyopathy"],"disease_name":"PKP2_Cardiomyopathy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/PKP2_Cardiomyopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/PKP2_Cardiomyopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/PKP2_Cardiomyopathy.html#dataset-geo-gse301005"]},{"id":"dataset:geo:gse301180","accession":"geo:GSE301180","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE301180","title":"Whole-genome sequencing and DigiPico of fallopian tube, tumor, and PBMC samples from high-grade serous ovarian cancer (HGSOC) patients [WGS/DigiPico]","alternate_titles":[],"description":"The fallopian tube (FT) has been proposed as a potential site of origin for high-grade serous ovarian cancer (HGSOC), supporting investigation of genomic alterations across matched tissues. This dataset includes whole-genome sequencing (WGS) and DigiPico data from matched samples, including peripheral blood mononuclear cells (PBMCs), fallopian tube tissue, and tumor tissue from HGSOC patients. The data support analysis of germline and somatic variants, copy number alterations (CNAs), and neoantigen prediction across matched sample types. This submission contains the WGS data DigiPico data associated with this study.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Fallopian Tube Cancer (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Fallopian_Tube_Cancer","name":"Fallopian Tube Cancer","kind":"Disorder","source_path":"kb/disorders/Fallopian_Tube_Cancer.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fallopian_Tube_Cancer.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Fallopian_Tube_Cancer.html#dataset-geo-gse301180"}],"context_names":["Fallopian Tube Cancer"],"disease_names":["Fallopian Tube Cancer"],"disease_name":"Fallopian Tube Cancer","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Fallopian_Tube_Cancer.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fallopian_Tube_Cancer.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Fallopian_Tube_Cancer.html#dataset-geo-gse301180"]},{"id":"dataset:geo:gse301183","accession":"geo:GSE301183","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE301183","title":"Using human urinary-derived renal epithelial cells for deep phenotyping of NPHP1 deletion and determining personalised response to novel therapeutics","alternate_titles":[],"description":"Nephronophthisis (NPHP) is an autosomal recessive tubulointerstitial nephropathy classified as a renal ciliopathy disorder and recognised as the leading genetic cause of kidney failure in children and young adults. NPHP1 is the most common genetic cause and encodes nephrocystin-1, a protein that plays crucial roles in the primary cilium and cellular junctions. Here we utilise personalised medicine approaches and deep phenotyping, which enable us to explore mechanistic pathways and identify potential therapeutic strategies.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[10],"sample_count":10,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40776899"],"publication_contexts":[{"context_id":"disorder:Nephronophthisis","publication":"PMID:40776899"}],"publication":"PMID:40776899","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40776899","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Nephronophthisis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Nephronophthisis","name":"Nephronophthisis","kind":"Disorder","source_path":"kb/disorders/Nephronophthisis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Nephronophthisis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Nephronophthisis.html#dataset-geo-gse301183"}],"context_names":["Nephronophthisis"],"disease_names":["Nephronophthisis"],"disease_name":"Nephronophthisis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Nephronophthisis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Nephronophthisis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Nephronophthisis.html#dataset-geo-gse301183"]},{"id":"dataset:geo:gse301280","accession":"geo:GSE301280","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE301280","title":"Spatial transcriptomics reveals dysfunctional lipid metabolism and abnormal pilosebaceous differentiation in acne vulgaris","alternate_titles":[],"description":"Targeted spatial transcriptomics of healthy, non-lesional, comedonal, and pustular human acne skin, focused on sebaceous differentiation, lipid metabolism, and retinoid signaling.","alternate_descriptions":["Spatial transcriptomics dataset in human acne lesions with an associated experimental component showing reduced pustule formation in a mouse model of high-fat-diet-induced folliculitis."],"data_types":["SPATIAL_TRANSCRIPTOMICS"],"data_type_labels":["Spatially resolved transcriptomics"],"data_type_label":"Spatially resolved transcriptomics","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[24],"sample_count":24,"conditions":["healthy skin","non-lesional acne skin","comedonal acne skin","pustular acne skin"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE301280","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE301280","reference_title":"Spatial transcriptomics reveals dysfunctional lipid metabolism and abnormal pilosebaceous differentiation in acne vulgaris","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"Here, we performed spatial transcriptomics on healthy, non-lesional, comedonal, and pustular acne skin using a custom panel targeting sebaceous differentiation, lipid metabolism, and retinoid signaling pathways.","explanation":"The GEO summary directly describes the disease-state spatial comparison."},{"reference":"GEO:GSE301280","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE301280","reference_title":"Spatial transcriptomics reveals dysfunctional lipid metabolism and abnormal pilosebaceous differentiation in acne vulgaris","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"Finally, we demonstrate that an AP-1 inhibitor, T-5224, strongly downregulates FABP5 in human keratinocytes and reduces pustule formation in a mouse model of high fat diet-induced folliculitis.","explanation":"The same GEO summary includes a linked mouse folliculitis model result, increasing disease relevance."}],"notes":["This is targeted spatial profiling rather than unbiased whole-transcriptome sequencing.","Included as a related pilosebaceous inflammation dataset with explicit folliculitis-model context."],"contexts":[{"id":"disorder:Acne_Vulgaris","name":"Acne Vulgaris","kind":"Disorder","source_path":"kb/disorders/Acne_Vulgaris.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Acne_Vulgaris.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Acne_Vulgaris.html#dataset-geo-gse301280"},{"id":"disorder:Folliculitis","name":"Folliculitis","kind":"Disorder","source_path":"kb/disorders/Folliculitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Folliculitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Folliculitis.html#dataset-geo-gse301280"}],"context_names":["Acne Vulgaris","Folliculitis"],"disease_names":["Acne Vulgaris","Folliculitis"],"disease_name":"Acne Vulgaris","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Acne_Vulgaris.yaml","kb/disorders/Folliculitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Acne_Vulgaris.yaml","https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Folliculitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Acne_Vulgaris.html#dataset-geo-gse301280","https://dismech.monarchinitiative.org/pages/disorders/Folliculitis.html#dataset-geo-gse301280"]},{"id":"dataset:geo:gse301378","accession":"geo:GSE301378","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE301378","title":"Single-cell RNA-seq and TCR profiling of tissue-resident memory T cells in the fallopian tube and matched ovarian cancer samples","alternate_titles":[],"description":"This study investigates the immune characteristics of tissue-resident memory T cells in the human fallopian tube in high-grade serous ovarian cancer (HGSOC). Single-cell RNA sequencing (scRNA-seq) and paired T-cell receptor sequencing (scTCR-seq) were performed on samples from non-cancerous fallopian tube tissue, metastatic omental tumors, and peripheral blood from HGSOC patients. The dataset enables analysis of tissue-resident T cell populations, clonal relationships across tissues, and immune features associated with tumor progression. These data provide a resource for studying tissue-resident T cell heterogeneity, clonal expansion, and tumor-associated immune responses in ovarian cancer.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[32],"sample_count":32,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Fallopian Tube Cancer (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Fallopian_Tube_Cancer","name":"Fallopian Tube Cancer","kind":"Disorder","source_path":"kb/disorders/Fallopian_Tube_Cancer.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fallopian_Tube_Cancer.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Fallopian_Tube_Cancer.html#dataset-geo-gse301378"}],"context_names":["Fallopian Tube Cancer"],"disease_names":["Fallopian Tube Cancer"],"disease_name":"Fallopian Tube Cancer","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Fallopian_Tube_Cancer.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fallopian_Tube_Cancer.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Fallopian_Tube_Cancer.html#dataset-geo-gse301378"]},{"id":"dataset:geo:gse301458","accession":"geo:GSE301458","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE301458","title":"Single-cell analysis of human fibrous dysplasia bone reveals a fibrotic transcriptome and somatic, mosaic GNAS R201H/C mutations in endothelial, perivascular, and stromal cells","alternate_titles":[],"description":"Genetic mosaicism is a leading cause of human disease across the lifespan. Improving the tools to detect somatic mosaicism and applying them to understand the cellular and molecular mechanisms that contribute to disease is of critical importance for improving human health. Fibrous dysplasia (FD) is a prototypical disease of Gs-GPCR activation caused by somatic, mosaic GNAS R201H/C mutations that result in fibrotic bone. Utilizing single-cell RNA sequencing and a unique GNAS genotyping strategy, we analyzed non-hematopoietic cells from FD and non-FD human bone. FD bone showed an altered fibroblast composition with a unique FD-specific osteoblastic cluster.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40848713"],"publication_contexts":[{"context_id":"disorder:Fibrous_Dysplasia","publication":"PMID:40848713"}],"publication":"PMID:40848713","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40848713","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Fibrous Dysplasia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Fibrous_Dysplasia","name":"Fibrous Dysplasia","kind":"Disorder","source_path":"kb/disorders/Fibrous_Dysplasia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fibrous_Dysplasia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Fibrous_Dysplasia.html#dataset-geo-gse301458"}],"context_names":["Fibrous Dysplasia"],"disease_names":["Fibrous Dysplasia"],"disease_name":"Fibrous Dysplasia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Fibrous_Dysplasia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fibrous_Dysplasia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Fibrous_Dysplasia.html#dataset-geo-gse301458"]},{"id":"dataset:geo:gse301492","accession":"geo:GSE301492","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE301492","title":"Transcriptome sequencing of Hodgkin lymphoma Hodgkin and Reed-Stenberg cells reveals escape from NK cell recognition and an unfolded protein response","alternate_titles":[],"description":"Bulk RNA-seq resource profiling flow-sorted primary Hodgkin/Reed-Sternberg cells, matched intratumoral non-neoplastic B cells, and cell lines to define malignant-cell transcriptional programs and immune-evasion biology in classic Hodgkin lymphoma.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[18],"sample_count":18,"conditions":["classic Hodgkin lymphoma Hodgkin/Reed-Sternberg cells","matched intratumoral non-neoplastic B cells"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE301492","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE301492","reference_title":"Transcriptome sequencing of Hodgkin lymphoma Hodgkin and Reed-Stenberg cells reveals escape from NK cell recognition and an unfolded protein response","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"To discover the molecular features that distinguish cHL, we deployed flow cytometric cell sorting and low-input RNA sequencing to generate full transcriptome data from viable, isolated Hodgkin and Red-Sternberg (HRS) cells from eighteen primary tumors, alongside matched intra-tumoral non-neoplastic B cells and four cell lines.","explanation":"This GEO series directly provides a patient-derived transcriptomic resource focused on malignant HRS cells and matched intratumoral B cells in classic Hodgkin lymphoma."}],"notes":[],"contexts":[{"id":"disorder:Classic_Hodgkin_Lymphoma","name":"Classic Hodgkin Lymphoma","kind":"Disorder","source_path":"kb/disorders/Classic_Hodgkin_Lymphoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Classic_Hodgkin_Lymphoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Classic_Hodgkin_Lymphoma.html#dataset-geo-gse301492"}],"context_names":["Classic Hodgkin Lymphoma"],"disease_names":["Classic Hodgkin Lymphoma"],"disease_name":"Classic Hodgkin Lymphoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Classic_Hodgkin_Lymphoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Classic_Hodgkin_Lymphoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Classic_Hodgkin_Lymphoma.html#dataset-geo-gse301492"]},{"id":"dataset:geo:gse301525","accession":"geo:GSE301525","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE301525","title":"Chromatin topology dynamics of dexamethasone-treated trabecular meshwork identifies 78 causal genes for intraocular pressure and primary open angle glaucoma","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["MULTI_OMICS"],"data_type_labels":["Multi Omics"],"data_type_label":"Multi Omics","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[131],"sample_count":131,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41890121"],"publication_contexts":[{"context_id":"disorder:Glaucoma","publication":"PMID:41890121"}],"publication":"PMID:41890121","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41890121","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Glaucoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Glaucoma","name":"Glaucoma","kind":"Disorder","source_path":"kb/disorders/Glaucoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Glaucoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Glaucoma.html#dataset-geo-gse301525"}],"context_names":["Glaucoma"],"disease_names":["Glaucoma"],"disease_name":"Glaucoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Glaucoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Glaucoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Glaucoma.html#dataset-geo-gse301525"]},{"id":"dataset:geo:gse301528","accession":"geo:GSE301528","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE301528","title":"Comprehensive evaluation of bone marrow microenvironment in patients with autoimmune hemolytic anemia: from trephine biopsy to single cell RNA sequencing.","alternate_titles":[],"description":"Bone marrow histology and clinical data from 97 selected AIHA patients, with single-cell RNA/TCR analysis in nine warm-AIHA patients across diagnosis, remission and relapse. Results and Table 1 report hypercellularity in 63/97, dyserythropoiesis in 74/97 and grade-1 reticulin fibrosis in 28/97; the abstract reverses the latter two percentages. The single-cell study used 12 patient specimens from nine individuals and three healthy donors, with treatment and cross-sectional relapse comparisons limiting causal interpretation. GEO sample_count denotes repository sample records rather than independent participants.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[18],"sample_count":18,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40854885"],"publication_contexts":[{"context_id":"disorder:Autoimmune_Hemolytic_Anemia","publication":"PMID:40854885"}],"publication":"PMID:40854885","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40854885","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Accession verified against GEO. The publication methods describe nine patients, with three repeat remission samples; diagnosis samples were collected after 2-5 days of steroids, and relapse samples followed prior therapies. The GEO record count is retained separately from the clinical participant count."],"contexts":[{"id":"disorder:Autoimmune_Hemolytic_Anemia","name":"Autoimmune Hemolytic Anemia","kind":"Disorder","source_path":"kb/disorders/Autoimmune_Hemolytic_Anemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autoimmune_Hemolytic_Anemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autoimmune_Hemolytic_Anemia.html#dataset-geo-gse301528"}],"context_names":["Autoimmune Hemolytic Anemia"],"disease_names":["Autoimmune Hemolytic Anemia"],"disease_name":"Autoimmune Hemolytic Anemia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Autoimmune_Hemolytic_Anemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autoimmune_Hemolytic_Anemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Autoimmune_Hemolytic_Anemia.html#dataset-geo-gse301528"]},{"id":"dataset:geo:gse30155","accession":"geo:GSE30155","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE30155","title":"Chromosomal profiles of high-grade cervical intraepithelial neoplasia relate to duration of preceding high-risk human papillomavirus infection","alternate_titles":[],"description":"High-grade cervical intraepithelial neoplasia (CIN2/3) represents a heterogeneous disease both with respect to clinical behaviour and chromosomal aberrations detected. We hypothesized that the extent of chromosomal aberrations reflects the duration of their existence. Chromosomal profiles were determined of CIN3 of women with a known 5 year history of high-risk human papillomavirus virus (hrHPV) infection, in which duration of prior hrHPV infection was considered a proxy for duration of CIN3 existence. Eleven women had a <5 year preceding hrHPV infection (CIN3<5yrPHI) and 24 had a PHI lasting ≥5 years (CIN3≥5yrPHI).","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[53],"sample_count":53,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:22020762"],"publication_contexts":[{"context_id":"disorder:Human_Papillomavirus_Infection","publication":"PMID:22020762"}],"publication":"PMID:22020762","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/22020762","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Human Papillomavirus Infection (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Human_Papillomavirus_Infection","name":"Human Papillomavirus Infection","kind":"Disorder","source_path":"kb/disorders/Human_Papillomavirus_Infection.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Human_Papillomavirus_Infection.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Human_Papillomavirus_Infection.html#dataset-geo-gse30155"}],"context_names":["Human Papillomavirus Infection"],"disease_names":["Human Papillomavirus Infection"],"disease_name":"Human Papillomavirus Infection","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Human_Papillomavirus_Infection.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Human_Papillomavirus_Infection.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Human_Papillomavirus_Infection.html#dataset-geo-gse30155"]},{"id":"dataset:geo:gse301626","accession":"geo:GSE301626","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE301626","title":"NGLY1-dependent conversion of N-glycosylated N to D is essential for transcription of proteasome genes","alternate_titles":[],"description":"Transcriptomic profiling of HeLa cells expressing glycan-less Nrf1 mutants (9NA and 9ND) in which all nine putative N-glycosylation sites were replaced, isolating the sequence-editing-specific contribution to Nrf1 function. This is the primary dataset behind the NFE2L1 sequence-editing node in this entry.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[9],"sample_count":9,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41468431"],"publication_contexts":[{"context_id":"disorder:NGLY1-congenital_disorder_of_deglycosylation","publication":"PMID:41468431"}],"publication":"PMID:41468431","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41468431","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Found by GEO DataSets search and verified against NCBI E-utilities on 2026-08-20; title, sample count, and organism are GEO's own values. DIRECT relevance - the series is the deposited data of the cited NGLY1 paper, not a gene-name match."],"contexts":[{"id":"disorder:NGLY1-congenital_disorder_of_deglycosylation","name":"NGLY1-congenital disorder of deglycosylation","kind":"Disorder","source_path":"kb/disorders/NGLY1-congenital_disorder_of_deglycosylation.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/NGLY1-congenital_disorder_of_deglycosylation.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/NGLY1-congenital_disorder_of_deglycosylation.html#dataset-geo-gse301626"}],"context_names":["NGLY1-congenital disorder of deglycosylation"],"disease_names":["NGLY1-congenital disorder of deglycosylation"],"disease_name":"NGLY1-congenital disorder of deglycosylation","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/NGLY1-congenital_disorder_of_deglycosylation.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/NGLY1-congenital_disorder_of_deglycosylation.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/NGLY1-congenital_disorder_of_deglycosylation.html#dataset-geo-gse301626"]},{"id":"dataset:geo:gse301690","accession":"geo:GSE301690","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE301690","title":"MAVS signaling of long-lived brain-resident myeloid cells is needed during viral encephalitis to adjust the transcriptome of CNS-infiltrating CD8+ T cells II","alternate_titles":[],"description":"Neurotropic viruses like vesicular stomatitis virus (VSV) can infect the central nervous system (CNS) through the olfactory route. Following intranasal instillation, VSV moves along the axons of olfactory sensory neurons to the olfactory bulb. While within the olfactory bulb the spread of the virus is controlled by microglia activation and the recruitment of peripheral leukocytes, some of the underlying mechanisms remain unknown. To investigate these mechanisms, we used mice with conditional deletions of the mitochondrial antiviral-signaling protein (MAVS), an adaptor for RIG-I-like receptor (RLR)-signaling.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[17],"sample_count":17,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40619428"],"publication_contexts":[{"context_id":"disorder:Viral_Encephalitis","publication":"PMID:40619428"}],"publication":"PMID:40619428","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40619428","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Viral Encephalitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Viral_Encephalitis","name":"Viral Encephalitis","kind":"Disorder","source_path":"kb/disorders/Viral_Encephalitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Viral_Encephalitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Viral_Encephalitis.html#dataset-geo-gse301690"}],"context_names":["Viral Encephalitis"],"disease_names":["Viral Encephalitis"],"disease_name":"Viral Encephalitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Viral_Encephalitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Viral_Encephalitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Viral_Encephalitis.html#dataset-geo-gse301690"]},{"id":"dataset:geo:gse301868","accession":"geo:GSE301868","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE301868","title":"Whole-blood transcriptomic response to whole-body hyperthermia in participants with major depressive disorder","alternate_titles":[],"description":"Depression is the leading cause of global disability according to the World Health Organization, and Major Depressive Disorder (MDD) makes up a majority of these cases. Current pharmacological interventions suffer from significant limitations and side effects, highlighting a need for novel therapeutic approaches. Whole-body hyperthermia (WBH) has been identified as a promising avenue of treatment; however, a comprehensive understanding of the mechanisms responsible for the antidepressant effects of WBH remains elusive.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[20],"sample_count":20,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42004495"],"publication_contexts":[{"context_id":"disorder:Major_Depressive_Disorder","publication":"PMID:42004495"}],"publication":"PMID:42004495","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42004495","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Major Depressive Disorder (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Major_Depressive_Disorder","name":"Major Depressive Disorder","kind":"Disorder","source_path":"kb/disorders/Major_Depressive_Disorder.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Major_Depressive_Disorder.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Major_Depressive_Disorder.html#dataset-geo-gse301868"}],"context_names":["Major Depressive Disorder"],"disease_names":["Major Depressive Disorder"],"disease_name":"Major Depressive Disorder","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Major_Depressive_Disorder.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Major_Depressive_Disorder.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Major_Depressive_Disorder.html#dataset-geo-gse301868"]},{"id":"dataset:geo:gse301876","accession":"geo:GSE301876","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE301876","title":"Spatial transcriptomic profiling of alveoli and granuloma regions in patients with active pulmonary tuberculosis","alternate_titles":[],"description":"Spatial transcriptomic profiling was performed using the GeoMx DSP Whole Transcriptome Atlas to measure expression of over 18,000 genes in alveoli and granuloma core and mantle regions from patients with active pulmonary tuberculosis. Differential gene expression revealed region-specific transcriptional profiles, including signatures related to antimicrobial response and lipid metabolism.","alternate_descriptions":[],"data_types":["SPATIAL_TRANSCRIPTOMICS"],"data_type_labels":["Spatially resolved transcriptomics"],"data_type_label":"Spatially resolved transcriptomics","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[180],"sample_count":180,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40791339"],"publication_contexts":[{"context_id":"disorder:Tuberculosis","publication":"PMID:40791339"}],"publication":"PMID:40791339","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40791339","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Tuberculosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Tuberculosis","name":"Tuberculosis","kind":"Disorder","source_path":"kb/disorders/Tuberculosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Tuberculosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Tuberculosis.html#dataset-geo-gse301876"}],"context_names":["Tuberculosis"],"disease_names":["Tuberculosis"],"disease_name":"Tuberculosis","same_context_model_ids":["model:kb/disorders/Tuberculosis.yaml:Autologous iPSC-derived alveolus-on-chip (iLoC) Mtb infection model"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Tuberculosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Tuberculosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Tuberculosis.html#dataset-geo-gse301876"]},{"id":"dataset:geo:gse301891","accession":"geo:GSE301891","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE301891","title":"RNA-Seq Analysis of Fibroblast-Like Synoviocytes Treated With Lutein in a Rheumatoid Arthritis Context","alternate_titles":[],"description":"Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation and progressive joint destruction. Although lutein is known for its antioxidant and anti-inflammatory properties, its effects on gene expression in RA-associated synoviocytes remain unclear. In this study, we performed RNA sequencing to investigate transcriptomic changes in fibroblast-like synoviocytes (FLS) treated with lutein. Differentially expressed genes were identified and analyzed using Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) to explore relevant biological processes and molecular networks.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42328127"],"publication_contexts":[{"context_id":"disorder:Rheumatoid_Arthritis","publication":"PMID:42328127"}],"publication":"PMID:42328127","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42328127","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Rheumatoid Arthritis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Rheumatoid_Arthritis","name":"Rheumatoid Arthritis","kind":"Disorder","source_path":"kb/disorders/Rheumatoid_Arthritis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rheumatoid_Arthritis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Rheumatoid_Arthritis.html#dataset-geo-gse301891"}],"context_names":["Rheumatoid Arthritis"],"disease_names":["Rheumatoid Arthritis"],"disease_name":"Rheumatoid Arthritis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Rheumatoid_Arthritis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rheumatoid_Arthritis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Rheumatoid_Arthritis.html#dataset-geo-gse301891"]},{"id":"dataset:geo:gse302095","accession":"geo:GSE302095","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE302095","title":"Validation of bronchial airway gene expression associated with bronchiectasis in nasal epithelium","alternate_titles":[],"description":"Objectives: Examination of bronchial epithelium-derived gene expression signature of bronchiectasis (BE) in nasal epithelium. Methods: We studied 220 participants from the Detection of Early Lung Cancer Among Military Personnel study with bulk RNA-seq of nasal epithelium brushings. Gene set enrichment analysis (GSEA) was used to examine whether genes previously identified as increased or decreased in the bronchial epithelium of individuals with radiologic BE are significantly enriched among the genes most significantly altered in the nasal epithelium.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[132],"sample_count":132,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42094231"],"publication_contexts":[{"context_id":"disorder:Bronchiectasis","publication":"PMID:42094231"}],"publication":"PMID:42094231","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42094231","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Bronchiectasis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Bronchiectasis","name":"Bronchiectasis","kind":"Disorder","source_path":"kb/disorders/Bronchiectasis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bronchiectasis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Bronchiectasis.html#dataset-geo-gse302095"}],"context_names":["Bronchiectasis"],"disease_names":["Bronchiectasis"],"disease_name":"Bronchiectasis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Bronchiectasis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bronchiectasis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Bronchiectasis.html#dataset-geo-gse302095"]},{"id":"dataset:geo:gse302248","accession":"geo:GSE302248","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE302248","title":"BCAT1 as a critical regulator of human chondrosarcoma progression and differentiation through enzymatic and non-enzymatic mechanisms","alternate_titles":[],"description":"Human chondrosarcoma is a malignant bone tumor with a poor prognosis due to its resistance to conventional therapies. In this study, we investigated the role of Branched-Chain Amino Acid Transaminase 1 (BCAT1) in chondrosarcoma pathogenesis. BCAT1 depletion impairs proliferation and tumorigenicity both in vitro and in vivo in a xenograft model, underscoring its oncogenic role. Transcriptome analyses revealed that BCAT1 suppresses the chondrocyte differentiation pathway by inhibiting the expression of SOX9, a master regulator of normal chondrogenesis, through epigenetic regulation.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[16],"sample_count":16,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Chondrosarcoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Chondrosarcoma","name":"Chondrosarcoma","kind":"Disorder","source_path":"kb/disorders/Chondrosarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chondrosarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chondrosarcoma.html#dataset-geo-gse302248"}],"context_names":["Chondrosarcoma"],"disease_names":["Chondrosarcoma"],"disease_name":"Chondrosarcoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chondrosarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chondrosarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chondrosarcoma.html#dataset-geo-gse302248"]},{"id":"dataset:geo:gse302512","accession":"geo:GSE302512","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE302512","title":"Immune checkpoint inhibitor-induced myocarditis is dependent on CD8 T cell-derived TNF and TNFR2 signaling","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"house mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41718716"],"publication_contexts":[{"context_id":"disorder:Myocarditis","publication":"PMID:41718716"}],"publication":"PMID:41718716","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41718716","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Murine model of checkpoint-inhibitor myocarditis, supporting the CD8 T cell arm of the Checkpoint Withdrawal node. Model-organism data, not human."],"contexts":[{"id":"disorder:Myocarditis","name":"Myocarditis","kind":"Disorder","source_path":"kb/disorders/Myocarditis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myocarditis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Myocarditis.html#dataset-geo-gse302512"}],"context_names":["Myocarditis"],"disease_names":["Myocarditis"],"disease_name":"Myocarditis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Myocarditis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myocarditis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Myocarditis.html#dataset-geo-gse302512"]},{"id":"dataset:geo:gse302772","accession":"geo:GSE302772","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE302772","title":"Expressed mutated genes in Sezary syndrome and their potential prognostic value in patients treated with Extracorporeal Photopheresis","alternate_titles":[],"description":"Background. Sézary syndrome (SS) is an aggressive and leukemic variant of Cutaneous T-cell Lymphoma (CTCL) with an incidence of 1-case per million people per year. It is characterized by a complex and heterogeneous profile of genetic alterations that has so far precluded the development of a specific and definitive therapeutic intervention.Methods. Deep-RNA-sequencing (RNA-seq) data were used to analyze the single nucleotide variants (SNVs) carried by 128 putative CTCL-driver genes, previously identified as mutated in genomic studies, in longitudinal SS samples collected from 17 patients subjected to extracorporeal photopheresis (ECP) with Interferon-α.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[40],"sample_count":40,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40918137"],"publication_contexts":[{"context_id":"disorder:Sezary_Syndrome","publication":"PMID:40918137"}],"publication":"PMID:40918137","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40918137","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Sezary Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Sezary_Syndrome","name":"Sezary Syndrome","kind":"Disorder","source_path":"kb/disorders/Sezary_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sezary_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Sezary_Syndrome.html#dataset-geo-gse302772"}],"context_names":["Sezary Syndrome"],"disease_names":["Sezary Syndrome"],"disease_name":"Sezary Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Sezary_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sezary_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Sezary_Syndrome.html#dataset-geo-gse302772"]},{"id":"dataset:geo:gse302854","accession":"geo:GSE302854","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE302854","title":"Differential Transcriptome Features of Peripheral Blood Mononuclear Cells in Pulmonary Sarcoidosis with and without Extrapulmonary Lesions","alternate_titles":[],"description":"Sarcoidosis is a systemic granulomatous disease of unknown etiology. Pulmonary sarcoidosis with extrapulmonary lesions (EPL), especially in cardiac sarcoidosis, is associated with poor prognosis. The transcriptome features of peripheral blood mononuclear cells (PBMCs) could be crucial in sarcoidosis pathogenesis. However, the gene expression characteristics associated with EPL development in pulmonary sarcoidosis remain unknown. Therefore, we investigated gene expression patterns associated with the development of EPL in pulmonary sarcoidosis. First, we conducted trascriptome analysis between patients with pulmonary sarcoidosis and healthy controls.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[40],"sample_count":40,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41463010"],"publication_contexts":[{"context_id":"disorder:Sarcoidosis","publication":"PMID:41463010"}],"publication":"PMID:41463010","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41463010","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Sarcoidosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Sarcoidosis","name":"Sarcoidosis","kind":"Disorder","source_path":"kb/disorders/Sarcoidosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sarcoidosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Sarcoidosis.html#dataset-geo-gse302854"}],"context_names":["Sarcoidosis"],"disease_names":["Sarcoidosis"],"disease_name":"Sarcoidosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Sarcoidosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sarcoidosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Sarcoidosis.html#dataset-geo-gse302854"]},{"id":"dataset:geo:gse302961","accession":"geo:GSE302961","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE302961","title":"Altered miRNA cargo of endometrial extracellular vesicles in endometriosis: potential implications for pregnancy outcomes","alternate_titles":[],"description":"Study question: Is the miRNA cargo of extracellular vesicles (EVs) secreted by the eutopic endometrium from women with endometriosis involved in its pathogenesis and related infertility? Summary answer: Data suggest that EVs secreted by primary endometrial epithelial cells from women with endometriosis transport an altered miRNA cargo that modulates biological processes related to endometriosis pathogenesis and pregnancy disorders. Main results and the role of chance: EVs had a mean size of 171 nm and expressed the EV protein markers CD63, CD9, and CD81. TEM corroborated EV cup-shaped morphology. Principal Component Analysis (PCA) revealed differentiated behavior between groups.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[7],"sample_count":7,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42282918"],"publication_contexts":[{"context_id":"disorder:Endometriosis","publication":"PMID:42282918"}],"publication":"PMID:42282918","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42282918","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Endometriosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Endometriosis","name":"Endometriosis","kind":"Disorder","source_path":"kb/disorders/Endometriosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Endometriosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Endometriosis.html#dataset-geo-gse302961"}],"context_names":["Endometriosis"],"disease_names":["Endometriosis"],"disease_name":"Endometriosis","same_context_model_ids":["model:kb/disorders/Endometriosis.yaml:Droplet-based microfluidic protease-activity profiling platform (PrAMA; MIT Griffith/Han)"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Endometriosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Endometriosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Endometriosis.html#dataset-geo-gse302961"]},{"id":"dataset:geo:gse303169","accession":"geo:GSE303169","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE303169","title":"RNAseq analyses of Esophageal biopsies from proton pump inhibitor (PPI)-responsive and PPI-unresponsive Pediatric patients with Eosinophilic Esophagitis.","alternate_titles":[],"description":"Clinical trials have identified two distinct eosinophilic esophagitis (EoE) treatment phenotypes, proton pump inhibitor (PPI)-responsive (PPI-R) and PPI-unresponsive (PPI-UR). Herein, we performed clinical, endoscopic, and histologic evaluation of esophageal biopsies from pediatric PPI-R and PPI-UR EoE individuals prior to PPI therapy (diagnosis) and following PPI trial. RNAseq analyses of esophageal biopsy samples revealed common immune and inflammatory transcriptional signatures in both PPI-R EoE and PPI-UR EoE at diagnosis and distinct signatures enriched for processes related to neuropeptide signaling and cell cycle and division.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[25],"sample_count":25,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41059573"],"publication_contexts":[{"context_id":"disorder:Eosinophilic_Esophagitis","publication":"PMID:41059573"}],"publication":"PMID:41059573","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41059573","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Eosinophilic Esophagitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Eosinophilic_Esophagitis","name":"Eosinophilic Esophagitis","kind":"Disorder","source_path":"kb/disorders/Eosinophilic_Esophagitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Eosinophilic_Esophagitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Eosinophilic_Esophagitis.html#dataset-geo-gse303169"}],"context_names":["Eosinophilic Esophagitis"],"disease_names":["Eosinophilic Esophagitis"],"disease_name":"Eosinophilic Esophagitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Eosinophilic_Esophagitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Eosinophilic_Esophagitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Eosinophilic_Esophagitis.html#dataset-geo-gse303169"]},{"id":"dataset:geo:gse303282","accession":"geo:GSE303282","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE303282","title":"Cathelicidin LL-37-induced transcriptome of human keratinocyte identifies chemokine CXCL10 link to T cell-mediated rosacea pathogenesis via JAK-1/STAT-1 pathway","alternate_titles":[],"description":"Human keratinocyte microarray dataset modeling LL-37-driven rosacea-like inflammation in vitro to resolve chemokine and JAK-STAT signaling outputs downstream of cathelicidin exposure.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":["LL-37-treated primary keratinocytes","untreated primary keratinocytes"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE303282","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE303282","reference_title":"Cathelicidin LL-37-induced transcriptome of human keratinocyte identifies chemokine CXCL10 link to T cell-mediated rosacea pathogenesis via JAK-1/STAT-1 pathway","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Mechanistically, LL-37 induced CXCL10 production relied on JAK-1/STAT-1 signaling pathway.","explanation":"This in vitro transcriptomic dataset is directly relevant to the cathelicidin and STAT-linked mechanism nodes in rosacea."}],"notes":[],"contexts":[{"id":"disorder:Rosacea","name":"Rosacea","kind":"Disorder","source_path":"kb/disorders/Rosacea.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rosacea.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Rosacea.html#dataset-geo-gse303282"}],"context_names":["Rosacea"],"disease_names":["Rosacea"],"disease_name":"Rosacea","same_context_model_ids":["model:kb/disorders/Rosacea.yaml:HaCaT keratinocytes under simulated rosacea conditions","model:kb/disorders/Rosacea.yaml:Paired lesional and non-lesional papulopustular rosacea skin explants","model:kb/disorders/Rosacea.yaml:SZ95 sebocyte and live Demodex mite co-culture"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Rosacea.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rosacea.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Rosacea.html#dataset-geo-gse303282"]},{"id":"dataset:geo:gse303418","accession":"geo:GSE303418","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE303418","title":"Selective inhibition of BRAF and CRAF sensitizes NF1-deficient malignant peripheral nerve sheath tumors to MEK inhibitors","alternate_titles":[],"description":"Background: Treatment for patients with malignant peripheral nerve sheath tumors (MPNST) is an unmet clinical need. Loss of NF1 in MPNST leads to hyperactivation of RAS oncoproteins, however little is known about relevant downstream oncogenic signaling and effective targeted therapies in MPNST are still lacking. Methods: Conditional gene expression, CRISPR-CAS9, and shRNA-mediated knockdown were used to perform gain/loss-of-function experiments to explore the effect of reconstituting the GTPase-activating protein-related domain of NF1 or knockdown of A/B/CRAF kinases on ERK signaling output and MPNST cell growth.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[36],"sample_count":36,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41023593"],"publication_contexts":[{"context_id":"disorder:Malignant_Peripheral_Nerve_Sheath_Tumor","publication":"PMID:41023593"}],"publication":"PMID:41023593","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41023593","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Malignant Peripheral Nerve Sheath Tumor (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Malignant_Peripheral_Nerve_Sheath_Tumor","name":"Malignant Peripheral Nerve Sheath Tumor","kind":"Disorder","source_path":"kb/disorders/Malignant_Peripheral_Nerve_Sheath_Tumor.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Malignant_Peripheral_Nerve_Sheath_Tumor.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Malignant_Peripheral_Nerve_Sheath_Tumor.html#dataset-geo-gse303418"}],"context_names":["Malignant Peripheral Nerve Sheath Tumor"],"disease_names":["Malignant Peripheral Nerve Sheath Tumor"],"disease_name":"Malignant Peripheral Nerve Sheath Tumor","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Malignant_Peripheral_Nerve_Sheath_Tumor.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Malignant_Peripheral_Nerve_Sheath_Tumor.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Malignant_Peripheral_Nerve_Sheath_Tumor.html#dataset-geo-gse303418"]},{"id":"dataset:geo:gse303481","accession":"geo:GSE303481","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE303481","title":"Spatio-temporal interaction of immune and renal cells determines glomerular crescent formation in autoimmune kidney disease","alternate_titles":[],"description":"Rapidly progressive glomerulonephritis (RPGN) is the most aggressive group of autoimmune kidney disease with the worst prognosis. Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis, anti-glomerular basement membrane (anti-GBM) and lupus nephritis are the most common causes of RPGN and are characterized by the formation of glomerular crescents and infiltration of leukocytes that eventually lead to glomerulosclerosis and kidney failure.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[15],"sample_count":15,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41028563"],"publication_contexts":[{"context_id":"disorder:Anti-GBM_Disease","publication":"PMID:41028563"}],"publication":"PMID:41028563","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41028563","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Anti-Glomerular Basement Membrane Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Anti-GBM_Disease","name":"Anti-Glomerular Basement Membrane Disease","kind":"Disorder","source_path":"kb/disorders/Anti-GBM_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Anti-GBM_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Anti-Glomerular_Basement_Membrane_Disease.html#dataset-geo-gse303481"}],"context_names":["Anti-Glomerular Basement Membrane Disease"],"disease_names":["Anti-Glomerular Basement Membrane Disease"],"disease_name":"Anti-Glomerular Basement Membrane Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Anti-GBM_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Anti-GBM_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Anti-Glomerular_Basement_Membrane_Disease.html#dataset-geo-gse303481"]},{"id":"dataset:geo:gse303609","accession":"geo:GSE303609","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE303609","title":"Dermatomyositis is characterized by JAK1-mediated monocyte-driven vasculopathy and inflammation","alternate_titles":[],"description":"Dermatomyositis (DM) is a rare yet devastating autoimmune disease characterized by inflammatory and vasculopathic changes in skin and muscle. DM and systemic lupus erythematosus (lupus) skin lesions have overlapping clinical and histopathological features, yet disparate responses to available therapeutics. DM skin disease is often relapsing and recalcitrant. To investigate DM immunopathogenesis, non-lesional skin, lesional skin, and circulating immune cells from DM patients were analyzed using single-cell RNA-sequencing. Samples were analyzed in parallel with lesional and non-lesional lupus skin, healthy control skin, and peripheral blood.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[34],"sample_count":34,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41442501"],"publication_contexts":[{"context_id":"disorder:Dermatomyositis","publication":"PMID:41442501"}],"publication":"PMID:41442501","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41442501","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Dermatomyositis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Dermatomyositis","name":"Dermatomyositis","kind":"Disorder","source_path":"kb/disorders/Dermatomyositis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dermatomyositis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Dermatomyositis.html#dataset-geo-gse303609"}],"context_names":["Dermatomyositis"],"disease_names":["Dermatomyositis"],"disease_name":"Dermatomyositis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Dermatomyositis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dermatomyositis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Dermatomyositis.html#dataset-geo-gse303609"]},{"id":"dataset:geo:gse303749","accession":"geo:GSE303749","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE303749","title":"mRNA signatures of a T-cell driven Limbic Encephalitis mouse model","alternate_titles":[],"description":"To determine the key transcription factors and molecular pathways involved in Limbic Encephalitis (LE), we analyzed immune cell-driven transcriptional changes in a newly developed mouse model of CD8+ T cell-mediated LE. This murine model (OVA-CD8+ LE) recapitulates the essential phenotypic features observed in human cytotoxic T lymphocyte (CTL)-induced LE, including neuroinflammation and seizure susceptibility. In a time series approach 2, 5, 8 and 28 days post-injection hippocampal tissue was harvested for RNA sequencing analysis.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[31],"sample_count":31,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42415095"],"publication_contexts":[{"context_id":"disorder:Limbic_Encephalitis","publication":"PMID:42415095"}],"publication":"PMID:42415095","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42415095","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Limbic Encephalitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Limbic_Encephalitis","name":"Limbic Encephalitis","kind":"Disorder","source_path":"kb/disorders/Limbic_Encephalitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Limbic_Encephalitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Limbic_Encephalitis.html#dataset-geo-gse303749"}],"context_names":["Limbic Encephalitis"],"disease_names":["Limbic Encephalitis"],"disease_name":"Limbic Encephalitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Limbic_Encephalitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Limbic_Encephalitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Limbic_Encephalitis.html#dataset-geo-gse303749"]},{"id":"dataset:geo:gse303810","accession":"geo:GSE303810","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE303810","title":"snRNA-seq profiles distinguish anti-Drebrin- and anti-GAD65-positive encephalitis","alternate_titles":[],"description":"Autoantibodies (ABs) against intracellular proteins, including glutamate-decarboxylase 65 (anti-GAD65), are increasingly recognized in autoimmune and limbic encephalitis (AE/LE). Anti-GAD65 LE frequently progresses into severe temporal lobe epilepsy (TLE), neuropathologically characterized by hippocampal sclerosis (HS) and variable cytotoxic T lymphocytes (CTLs) infiltration. Recently, we have identified Drebrin as a novel intracellular target protein of ABs in patients suspicious for AE.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[8],"sample_count":8,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42415095"],"publication_contexts":[{"context_id":"disorder:Limbic_Encephalitis","publication":"PMID:42415095"}],"publication":"PMID:42415095","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42415095","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Limbic Encephalitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Limbic_Encephalitis","name":"Limbic Encephalitis","kind":"Disorder","source_path":"kb/disorders/Limbic_Encephalitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Limbic_Encephalitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Limbic_Encephalitis.html#dataset-geo-gse303810"}],"context_names":["Limbic Encephalitis"],"disease_names":["Limbic Encephalitis"],"disease_name":"Limbic Encephalitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Limbic_Encephalitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Limbic_Encephalitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Limbic_Encephalitis.html#dataset-geo-gse303810"]},{"id":"dataset:geo:gse303840","accession":"geo:GSE303840","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE303840","title":"Racial discrepancies in placental gene expressions between Black and White healthy and preeclampsia patients of equivalent BMI and blood pressure in a Southeastern USA cohort","alternate_titles":[],"description":"Preeclampsia is a devastating hypertensive disorder of pregnancy that afflicts between 5-10% of pregnancies in the US, with a higher prevalence in the southern regions of the United States. Black pregnant women are disproportionally at higher risk for preeclampsia onset and severity of disease than other racial groups, including White women. Although this has been recognized in the maternal fetal medicine literature for many years, the underlying mechanism(s) for this racial disparity are unclear. One confounding issue with many studies of racial discrepancies in pregnant women is differences in comorbidities between racial groups.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[24],"sample_count":24,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Preeclampsia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Preeclampsia","name":"Preeclampsia","kind":"Disorder","source_path":"kb/disorders/Preeclampsia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Preeclampsia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Preeclampsia.html#dataset-geo-gse303840"}],"context_names":["Preeclampsia"],"disease_names":["Preeclampsia"],"disease_name":"Preeclampsia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Preeclampsia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Preeclampsia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Preeclampsia.html#dataset-geo-gse303840"]},{"id":"dataset:geo:gse303899","accession":"geo:GSE303899","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE303899","title":"Unraveling the Epigenetic Landscape of Sarcopenic Obesity: Insights into DNA Methylation Mechanisms from a Pilot Study in Older Women","alternate_titles":[],"description":"DNA methylation profiling in sarcopenic obesity, the only human dataset among the candidates surfaced for this entry. Relevant to has_subtypes#Sarcopenic obesity and to the epigenetic component of the ageing muscle phenotype.","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[32],"sample_count":32,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41578880"],"publication_contexts":[{"context_id":"disorder:Sarcopenia","publication":"PMID:41578880"}],"publication":"PMID:41578880","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41578880","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Selected by manual relevance triage from `just discover-datasets Sarcopenia` and accession-verified with `just verify-datasets`. No evidence block: an evidence item needs an exact quote from the cited abstract supporting a specific claim, and this record asserts only that the dataset exists and is on topic."],"contexts":[{"id":"disorder:Sarcopenia","name":"Sarcopenia","kind":"Disorder","source_path":"kb/disorders/Sarcopenia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sarcopenia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Sarcopenia.html#dataset-geo-gse303899"}],"context_names":["Sarcopenia"],"disease_names":["Sarcopenia"],"disease_name":"Sarcopenia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Sarcopenia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sarcopenia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Sarcopenia.html#dataset-geo-gse303899"]},{"id":"dataset:geo:gse303922","accession":"geo:GSE303922","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE303922","title":"Transcriptomic Evidence of Acquired Cannabis Hypersensitivity in Cannabinoid Hyperemesis Syndrome","alternate_titles":[],"description":"Cannabinoid hyperemesis syndrome (CHS) is a paradoxical and increasingly prevalent disorder characterized by recurrent vomiting in people with chronic cannabis use. Despite its growing clinical impact, the underlying mechanisms remain poorly understood. Contrary to prevailing hypotheses implicating the endogenous cannabinoid system (ECS), we found no significant changes in ECS-related transcripts. Instead, CHS was associated with marked activation of the adaptive immune system, including upregulation of B-cell related immunoglobin transcripts and altered expression of T cell, monocyte, and neutrophil-related transcripts.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[14],"sample_count":14,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Cannabis Hyperemesis Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Cannabis_Hyperemesis_Syndrome","name":"Cannabis Hyperemesis Syndrome","kind":"Disorder","source_path":"kb/disorders/Cannabis_Hyperemesis_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cannabis_Hyperemesis_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cannabis_Hyperemesis_Syndrome.html#dataset-geo-gse303922"}],"context_names":["Cannabis Hyperemesis Syndrome"],"disease_names":["Cannabis Hyperemesis Syndrome"],"disease_name":"Cannabis Hyperemesis Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cannabis_Hyperemesis_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cannabis_Hyperemesis_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cannabis_Hyperemesis_Syndrome.html#dataset-geo-gse303922"]},{"id":"dataset:geo:gse303993","accession":"geo:GSE303993","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE303993","title":"Developing Midbrain-like Organoid of Gaucher Disease as A Platform for Drug Assessment","alternate_titles":[],"description":"Gaucher disease (GD) is a lysosomal storage disorder caused by GBA1 mutations, leading to defective acid β-glucosidase (GCase) and accumulation of glucosylsphingolipids, causing inflammation and neurodegeneration. We developed midbrain-like organoids (MLOs) from induced pluripotent stem cells (iPSCs) of nGD patients with GBA1L444P/P415R and GBA1L444P/RecNcil mutations to model nGD brain pathogenesis. These nGD MLOs exhibited GCase deficiencies, reduced enzyme activities, lipids accumulation, transcriptomic alterations, and impaired dopaminergic neuron differentiation, mirroring nGD pathology.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42334452"],"publication_contexts":[{"context_id":"disorder:Gaucher_Disease","publication":"PMID:42334452"}],"publication":"PMID:42334452","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42334452","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Gaucher Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Gaucher_Disease","name":"Gaucher Disease","kind":"Disorder","source_path":"kb/disorders/Gaucher_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Gaucher_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Gaucher_Disease.html#dataset-geo-gse303993"}],"context_names":["Gaucher Disease"],"disease_names":["Gaucher Disease"],"disease_name":"Gaucher Disease","same_context_model_ids":["model:kb/disorders/Gaucher_Disease.yaml:CBE-treated murine macrophage conditioned-medium model","model:kb/disorders/Gaucher_Disease.yaml:GD1 patient bone marrow stromal cells"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Gaucher_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Gaucher_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Gaucher_Disease.html#dataset-geo-gse303993"]},{"id":"dataset:geo:gse304168","accession":"geo:GSE304168","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE304168","title":"mRNA Therapeutics Encoding Multiple Reparative Factors using Polyplex Nanomicelle Attenuating Myocardial Infarction","alternate_titles":[],"description":"Background: Gene therapy for heart failure has been explored using single factors such as angiogenic agents; however, clinical success remains limited. In this study, we investigated an alternative approach by directly administering mRNA encoding multiple genes that are transiently upregulated during cardiac recovery. Using a model in which heart function is restored through the administration of extracellular vesicles secreted by human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM-derived EVs), we aimed to evaluate the potential of multi-gene mRNA therapy for heart failure, being delivered using polyplex nanomicelles, which serve as an effective delivery system with superio...","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42272746"],"publication_contexts":[{"context_id":"disorder:Myocardial_Infarction","publication":"PMID:42272746"}],"publication":"PMID:42272746","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42272746","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Myocardial Infarction (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Myocardial_Infarction","name":"Myocardial Infarction","kind":"Disorder","source_path":"kb/disorders/Myocardial_Infarction.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myocardial_Infarction.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Myocardial_Infarction.html#dataset-geo-gse304168"}],"context_names":["Myocardial Infarction"],"disease_names":["Myocardial Infarction"],"disease_name":"Myocardial Infarction","same_context_model_ids":["model:kb/disorders/Myocardial_Infarction.yaml:Bioelectronically instrumented heart-on-a-chip under acute hypoxia","model:kb/disorders/Myocardial_Infarction.yaml:Epicardial-myocardial heart-on-a-chip model of ischemia-reperfusion injury","model:kb/disorders/Myocardial_Infarction.yaml:Human cardiac infarct organoid with an internal oxygen-diffusion gradient","model:kb/disorders/Myocardial_Infarction.yaml:Human heart-on-a-chip ischemia-reperfusion assay with endothelial extracellular vesicle rescue","model:kb/disorders/Myocardial_Infarction.yaml:Myocardial infarct border-zone-on-a-chip"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Myocardial_Infarction.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myocardial_Infarction.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Myocardial_Infarction.html#dataset-geo-gse304168"]},{"id":"dataset:geo:gse304352","accession":"geo:GSE304352","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE304352","title":"Transcriptome analysis of liver tissue from patients with Autoimmune Hepatitis, Primary Biliary Cholangitis, and Chronic Hepatitis B","alternate_titles":[],"description":"This study aims to identify immune-related genes in Autoimmune Hepatitis (AIH) by analyzing liver tissue transcriptomes. Bulk RNA sequencing was performed on liver biopsies from patients with AIH and two disease control groups: Primary Biliary Cholangitis (PBC) and Chronic Hepatitis B (CHB). Differential expression analysis was used to compare AIH against both control groups. By intersecting the resulting differentially expressed genes (DEGs) with immune gene databases, we identified 19 common immune-related DEGs (IRDEGs). Gene Ontology (GO) analysis of these genes highlighted functions related to lymphocyte-mediated immunity and T-cell receptor signaling.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[11],"sample_count":11,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42483202"],"publication_contexts":[{"context_id":"disorder:Primary_Biliary_Cholangitis","publication":"PMID:42483202"}],"publication":"PMID:42483202","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42483202","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Primary Biliary Cholangitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Primary_Biliary_Cholangitis","name":"Primary Biliary Cholangitis","kind":"Disorder","source_path":"kb/disorders/Primary_Biliary_Cholangitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Primary_Biliary_Cholangitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Biliary_Cholangitis.html#dataset-geo-gse304352"}],"context_names":["Primary Biliary Cholangitis"],"disease_names":["Primary Biliary Cholangitis"],"disease_name":"Primary Biliary Cholangitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Primary_Biliary_Cholangitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Primary_Biliary_Cholangitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Primary_Biliary_Cholangitis.html#dataset-geo-gse304352"]},{"id":"dataset:geo:gse304575","accession":"geo:GSE304575","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE304575","title":"LMNA p.H222P mutation causes contractile dysfunction via impaired mitochondrial calcium uptake in human cardiac laminopathy","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42478871"],"publication_contexts":[{"context_id":"disorder:Dilated_Cardiomyopathy_1A","publication":"PMID:42478871"}],"publication":"PMID:42478871","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42478871","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Human cardiac laminopathy model carrying LMNA p.H222P, the same allele as the knock-in mouse curated under animal_models."],"contexts":[{"id":"disorder:Dilated_Cardiomyopathy_1A","name":"Dilated Cardiomyopathy 1A","kind":"Disorder","source_path":"kb/disorders/Dilated_Cardiomyopathy_1A.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dilated_Cardiomyopathy_1A.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy_1A.html#dataset-geo-gse304575"}],"context_names":["Dilated Cardiomyopathy 1A"],"disease_names":["Dilated Cardiomyopathy 1A"],"disease_name":"Dilated Cardiomyopathy 1A","same_context_model_ids":["model:kb/disorders/Dilated_Cardiomyopathy_1A.yaml:Patient-derived LMNA-mutant iPSC cardiomyocytes"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Dilated_Cardiomyopathy_1A.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dilated_Cardiomyopathy_1A.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy_1A.html#dataset-geo-gse304575"]},{"id":"dataset:geo:gse305114","accession":"geo:GSE305114","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE305114","title":"Transcriptome profiling of FGL2-stimulated enteric neural crest cells to investigate metabolic dysregulation in Hirschsprung disease pathogenesis","alternate_titles":[],"description":"This dataset comprises bulk RNA sequencing data from primary mouse enteric neural crest cells (ENCCs) stimulated with fibrinogen-like protein 2 (FGL2) or left untreated as controls. ENCCs were isolated from embryonic day 14–15 C57BL/6J mice and cultured under defined conditions to ensure >95% expression of P75 and nestin markers. Following FGL2 stimulation, total RNA was extracted, and sequencing libraries were prepared using the NEBNext Ultra RNA Library Prep Kit for Illumina. Paired-end sequencing (2 × 150 bp) was performed on the Illumina NovaSeq 6000 platform.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[10],"sample_count":10,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40978140"],"publication_contexts":[{"context_id":"disorder:Hirschsprung_Disease","publication":"PMID:40978140"}],"publication":"PMID:40978140","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40978140","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Hirschsprung Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Hirschsprung_Disease","name":"Hirschsprung Disease","kind":"Disorder","source_path":"kb/disorders/Hirschsprung_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hirschsprung_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hirschsprung_Disease.html#dataset-geo-gse305114"}],"context_names":["Hirschsprung Disease"],"disease_names":["Hirschsprung Disease"],"disease_name":"Hirschsprung Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hirschsprung_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hirschsprung_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hirschsprung_Disease.html#dataset-geo-gse305114"]},{"id":"dataset:geo:gse305543","accession":"geo:GSE305543","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE305543","title":"Hepatocyte-specific MET deletion exacerbates acetaminophen-induced hepatotoxicity in mice","alternate_titles":[],"description":"Despite the well-known role of MET in liver regeneration following partial-hepatectomy (PHx), its role in the clinically-relevant acetaminophen (APAP)-induced liver injury (AILI) model remains unexplored. AILI markedly differs from PHx because it is associated with massive liver necrosis. This study aims to delineate the role of MET specifically in AILI. Hepatocyte-specific MET-KO mice were given a toxic-dose of APAP and assessed for hepatotoxicity/regeneration parameters. MET deletion strikingly exacerbated initial hepatotoxicity and impaired subsequent proliferative response, culminating in significant mortality.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[18],"sample_count":18,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41038273"],"publication_contexts":[{"context_id":"disorder:Acetaminophen_Hepatotoxicity","publication":"PMID:41038273"}],"publication":"PMID:41038273","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41038273","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Acetaminophen Hepatotoxicity (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Acetaminophen_Hepatotoxicity","name":"Acetaminophen Hepatotoxicity","kind":"Disorder","source_path":"kb/disorders/Acetaminophen_Hepatotoxicity.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Acetaminophen_Hepatotoxicity.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Acetaminophen_Hepatotoxicity.html#dataset-geo-gse305543"}],"context_names":["Acetaminophen Hepatotoxicity"],"disease_names":["Acetaminophen Hepatotoxicity"],"disease_name":"Acetaminophen Hepatotoxicity","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Acetaminophen_Hepatotoxicity.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Acetaminophen_Hepatotoxicity.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Acetaminophen_Hepatotoxicity.html#dataset-geo-gse305543"]},{"id":"dataset:geo:gse305622","accession":"geo:GSE305622","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE305622","title":"Proximal ganglionic intestine in Hirschsprung Disease is fibrotic and stiff","alternate_titles":[],"description":"Hirschsprung disease (HSCR) is a congenital intestinal disorder characterized by the absence of ganglia in the distal intestine. Despite surgical resection of the aganglionic intestine and pull-through surgery, HSCR patients still experience bowel dysfunction, indicating that latent abnormalities may also exist in the proximal ganglionic intestine. To elucidate possible causes of postoperative bowel dysfunction in HSCR, we investigated differences in the proximal ganglionic intestine using an animal model of HSCR (Ednrb-null mice) and validated our findings in tissue from human HSCR patients.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[16],"sample_count":16,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41666297"],"publication_contexts":[{"context_id":"disorder:Hirschsprung_Disease","publication":"PMID:41666297"}],"publication":"PMID:41666297","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41666297","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Hirschsprung Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Hirschsprung_Disease","name":"Hirschsprung Disease","kind":"Disorder","source_path":"kb/disorders/Hirschsprung_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hirschsprung_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hirschsprung_Disease.html#dataset-geo-gse305622"}],"context_names":["Hirschsprung Disease"],"disease_names":["Hirschsprung Disease"],"disease_name":"Hirschsprung Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hirschsprung_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hirschsprung_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hirschsprung_Disease.html#dataset-geo-gse305622"]},{"id":"dataset:geo:gse30596","accession":"geo:GSE30596","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE30596","title":"Isolation of novel multipotent neural crest-derived stem cells from adult human inferior turbinate","alternate_titles":[],"description":"Expression profiling of neural crest-derived stem cells isolated from adult human inferior turbinate respiratory epithelium. These stem cells express neural crest markers and demonstrate multipotent differentiation capacity. Relevant to ENS as it characterizes progenitor cells present in the turbinate tissue that is resected.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0005922","label":"inferior nasal concha","display_label":"inferior nasal concha","url":"http://purl.obolibrary.org/obo/UBERON_0005922"}],"sample_type_labels":["inferior nasal concha"],"sample_counts":[12],"sample_count":12,"conditions":["inferior turbinate stem cells","control"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["Illumina HumanHT-12 v4"],"platform":"Illumina HumanHT-12 v4","publications":["PMID:22128806"],"publication_contexts":[{"context_id":"disorder:Empty_Nose_Syndrome","publication":"PMID:22128806"}],"publication":"PMID:22128806","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/22128806","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Characterizes stem cell populations in the human inferior turbinate, the tissue most commonly resected in surgeries that lead to ENS."],"contexts":[{"id":"disorder:Empty_Nose_Syndrome","name":"Empty Nose Syndrome","kind":"Disorder","source_path":"kb/disorders/Empty_Nose_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Empty_Nose_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Empty_Nose_Syndrome.html#dataset-geo-gse30596"}],"context_names":["Empty Nose Syndrome"],"disease_names":["Empty Nose Syndrome"],"disease_name":"Empty Nose Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Empty_Nose_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Empty_Nose_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Empty_Nose_Syndrome.html#dataset-geo-gse30596"]},{"id":"dataset:geo:gse305960","accession":"geo:GSE305960","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE305960","title":"Investigating the mechanisms by which SMAD6 mutations cause tracheoesophageal birth defects","alternate_titles":[],"description":"Esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) are tracheoesophageal (TE) birth defects which affect 1 in 3000 live births in the United States. EA occurs when the esophagus fails to form a continuous tube from the oral cavity to the stomach and TEF occurs when there is an abnormal connection between the trachea and esophagus. The etiology of EA/TEF arises when the common foregut tube fails to properly separate into the esophagus and respiratory tract during early embryogenesis. This process is essential for proper organ function and involves complex molecular and morphological processes.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[54],"sample_count":54,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Esophageal Atresia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Esophageal_Atresia","name":"Esophageal Atresia","kind":"Disorder","source_path":"kb/disorders/Esophageal_Atresia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Esophageal_Atresia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Esophageal_Atresia.html#dataset-geo-gse305960"}],"context_names":["Esophageal Atresia"],"disease_names":["Esophageal Atresia"],"disease_name":"Esophageal Atresia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Esophageal_Atresia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Esophageal_Atresia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Esophageal_Atresia.html#dataset-geo-gse305960"]},{"id":"dataset:geo:gse306012","accession":"geo:GSE306012","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE306012","title":"Temporal inhibition of ADAM17 in fibroblasts reduces stiffness and promotes vascularization following myocardial infarction","alternate_titles":[],"description":"Myocardial infarction (MI) triggers a complex remodelling process that leads to heat failure if uncontrolled. A Disintegrin and metalloproteinase-17 (ADAM17), a transmembrane sheddase, is upregulated in patients with ischemic cardiomyopathy, colocalized to myofibroblasts (myoFB) in the infarct tissues. Fibroblasts are key players in post-MI scar formation and exist in different states with diverse functions. Using mice with inducible Adam17 deletion in homeostatic FBs (Adam17 FB-KD ), or activated FBs (Adam17 myoFB-KD ), we found that ADAM17 loss in homeostatic FBs impaired infarct formation post-MI and increased mortality due to left ventricular (LV) rupture.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[28],"sample_count":28,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41524432"],"publication_contexts":[{"context_id":"disorder:Myocardial_Infarction","publication":"PMID:41524432"}],"publication":"PMID:41524432","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41524432","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Myocardial Infarction (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Myocardial_Infarction","name":"Myocardial Infarction","kind":"Disorder","source_path":"kb/disorders/Myocardial_Infarction.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myocardial_Infarction.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Myocardial_Infarction.html#dataset-geo-gse306012"}],"context_names":["Myocardial Infarction"],"disease_names":["Myocardial Infarction"],"disease_name":"Myocardial Infarction","same_context_model_ids":["model:kb/disorders/Myocardial_Infarction.yaml:Bioelectronically instrumented heart-on-a-chip under acute hypoxia","model:kb/disorders/Myocardial_Infarction.yaml:Epicardial-myocardial heart-on-a-chip model of ischemia-reperfusion injury","model:kb/disorders/Myocardial_Infarction.yaml:Human cardiac infarct organoid with an internal oxygen-diffusion gradient","model:kb/disorders/Myocardial_Infarction.yaml:Human heart-on-a-chip ischemia-reperfusion assay with endothelial extracellular vesicle rescue","model:kb/disorders/Myocardial_Infarction.yaml:Myocardial infarct border-zone-on-a-chip"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Myocardial_Infarction.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myocardial_Infarction.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Myocardial_Infarction.html#dataset-geo-gse306012"]},{"id":"dataset:geo:gse306150","accession":"geo:GSE306150","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE306150","title":"Spatial gene expression profiling of aortitis samples.","alternate_titles":[],"description":"10X Xenium profiling of ascending aorta samples isolated from subjects with aortitis.","alternate_descriptions":[],"data_types":["SPATIAL_TRANSCRIPTOMICS"],"data_type_labels":["Spatially resolved transcriptomics"],"data_type_label":"Spatially resolved transcriptomics","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[10],"sample_count":10,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41948935"],"publication_contexts":[{"context_id":"disorder:Aortitis","publication":"PMID:41948935"}],"publication":"PMID:41948935","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41948935","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Aortitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. 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Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Ischemic_Stroke","name":"Ischemic Stroke","kind":"Disorder","source_path":"kb/disorders/Ischemic_Stroke.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ischemic_Stroke.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Ischemic_Stroke.html#dataset-geo-gse307081"}],"context_names":["Ischemic Stroke"],"disease_names":["Ischemic Stroke"],"disease_name":"Ischemic Stroke","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Ischemic_Stroke.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ischemic_Stroke.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Ischemic_Stroke.html#dataset-geo-gse307081"]},{"id":"dataset:geo:gse307095","accession":"geo:GSE307095","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE307095","title":"RNA-seq profiling of resting naive and CD27bright memory B cells and in vitro activated CD27bright memory B cells reveals differences in B-cell activation patterns in common variable immunodeficiency (CVID)","alternate_titles":[],"description":"To investigate the transcriptional differences during resting state and B-cell activation in healthy donors and patients with CVID, we sorted naive B cells and CD27bright memory B cells from the two groups and examined the resting state and TLR9 agonist (CpG)-activated CD27bright memory B cells.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[50],"sample_count":50,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41124223"],"publication_contexts":[{"context_id":"disorder:Common_Variable_Immunodeficiency","publication":"PMID:41124223"}],"publication":"PMID:41124223","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41124223","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Common Variable Immunodeficiency (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Common_Variable_Immunodeficiency","name":"Common Variable Immunodeficiency","kind":"Disorder","source_path":"kb/disorders/Common_Variable_Immunodeficiency.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Common_Variable_Immunodeficiency.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Common_Variable_Immunodeficiency.html#dataset-geo-gse307095"}],"context_names":["Common Variable Immunodeficiency"],"disease_names":["Common Variable Immunodeficiency"],"disease_name":"Common Variable Immunodeficiency","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Common_Variable_Immunodeficiency.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Common_Variable_Immunodeficiency.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Common_Variable_Immunodeficiency.html#dataset-geo-gse307095"]},{"id":"dataset:geo:gse307177","accession":"geo:GSE307177","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE307177","title":"CHN1 as a Predictive Biomarker for Atopic Dermatitis-related Depression","alternate_titles":[],"description":"The comorbidity of Atopic Dermatitis (AD) and depression has garnered increasing attention in recent years. Yet, the immunopathological mechanisms underlying this connection remain unclear. To bridge this gap, we collected peripheral blood mononuclear cell samples from 20 AD patients with and without depression, and performed RNA sequencing analysis. By integrating bioinformatics and machine learning techniques, we aimed to uncover the immune regulatory networks and identify key genetic markers for the depression comorbidity in AD patients. Our analysis revealed 394 differentially expressed genes in AD patients with depression as compared to those non-depression counterparts.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[20],"sample_count":20,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41333466"],"publication_contexts":[{"context_id":"disorder:Atopic_Dermatitis","publication":"PMID:41333466"}],"publication":"PMID:41333466","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41333466","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Atopic Dermatitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Atopic_Dermatitis","name":"Atopic Dermatitis","kind":"Disorder","source_path":"kb/disorders/Atopic_Dermatitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Atopic_Dermatitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Atopic_Dermatitis.html#dataset-geo-gse307177"}],"context_names":["Atopic Dermatitis"],"disease_names":["Atopic Dermatitis"],"disease_name":"Atopic Dermatitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Atopic_Dermatitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Atopic_Dermatitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Atopic_Dermatitis.html#dataset-geo-gse307177"]},{"id":"dataset:geo:gse307393","accession":"geo:GSE307393","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE307393","title":"Brimonidine protects IHC ribbon synapses and SGNs from noise-induced hearing loss","alternate_titles":[],"description":"Exposure to excessive noise levels can result in hearing impairment. Currently, there are no effective pharmacological interventions available for the prevention of noise-induced hearing loss. This study was designed to investigate the protective effects of brimonidine, an α2-adrenergic receptor agonist, against noise-induced inner ear damage in mice, as well as to explore the underlying mechanisms.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[17],"sample_count":17,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41953996"],"publication_contexts":[{"context_id":"disorder:Noise_Induced_Hearing_Loss","publication":"PMID:41953996"}],"publication":"PMID:41953996","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41953996","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Noise Induced Hearing Loss (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Noise_Induced_Hearing_Loss","name":"Noise Induced Hearing Loss","kind":"Disorder","source_path":"kb/disorders/Noise_Induced_Hearing_Loss.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Noise_Induced_Hearing_Loss.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Noise_Induced_Hearing_Loss.html#dataset-geo-gse307393"}],"context_names":["Noise Induced Hearing Loss"],"disease_names":["Noise Induced Hearing Loss"],"disease_name":"Noise Induced Hearing Loss","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Noise_Induced_Hearing_Loss.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Noise_Induced_Hearing_Loss.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Noise_Induced_Hearing_Loss.html#dataset-geo-gse307393"]},{"id":"dataset:geo:gse307443","accession":"geo:GSE307443","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE307443","title":"Loss of cell-autonomously secreted laminin-α2 drives muscle stem cell dysfunction in LAMA2-related muscular dystrophy","alternate_titles":[],"description":"Human iPSC-derived myogenic precursor cells, LAMA2-deficient versus control. One of the few human-cell datasets in this disease, and directly relevant to the Abortive Muscle Regeneration node because it addresses whether laminin-alpha2 acts on the progenitor cell itself rather than only on the mature fibre.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[8],"sample_count":8,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:6482","label":"LAMA2","display_label":"LAMA2","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/6482"}],"genes":["LAMA2"],"platforms":[],"platform":null,"publications":["PMID:41309582"],"publication_contexts":[{"context_id":"disorder:Congenital_Merosin-deficient_Muscular_Dystrophy_1A","publication":"PMID:41309582"}],"publication":"PMID:41309582","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41309582","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Recorded without an evidence block. The repository summary states the study's motivation rather than its result, so there is no sentence in the cached record that would substantively support a specific curated claim; quoting the motivation would be a topic snippet rather than a finding."],"contexts":[{"id":"disorder:Congenital_Merosin-deficient_Muscular_Dystrophy_1A","name":"Congenital Merosin-deficient Muscular Dystrophy 1A","kind":"Disorder","source_path":"kb/disorders/Congenital_Merosin-deficient_Muscular_Dystrophy_1A.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Congenital_Merosin-deficient_Muscular_Dystrophy_1A.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Congenital_Merosin-deficient_Muscular_Dystrophy_1A.html#dataset-geo-gse307443"}],"context_names":["Congenital Merosin-deficient Muscular Dystrophy 1A"],"disease_names":["Congenital Merosin-deficient Muscular Dystrophy 1A"],"disease_name":"Congenital Merosin-deficient Muscular Dystrophy 1A","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Congenital_Merosin-deficient_Muscular_Dystrophy_1A.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Congenital_Merosin-deficient_Muscular_Dystrophy_1A.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Congenital_Merosin-deficient_Muscular_Dystrophy_1A.html#dataset-geo-gse307443"]},{"id":"dataset:geo:gse307588","accession":"geo:GSE307588","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE307588","title":"Spatial profiling of hypoxic injury in human kidney organoids","alternate_titles":[],"description":"This dataset relates to a spatial transcriptomic experiment investigating potential reparative and inflammatory roles for macrophages in human iPSC-derived kidney organoids exposed to hypoxic injury, linked to a broader study of ischaemic kidney injury and repair in this model (https://doi.org/10.1101/2023.10.04.558359). Acute kidney injury (AKI) is a common clinical disorder linked to high rates of illness and death. Ischaemia is a leading cause of AKI, where reduced blood flow to the kidney triggers hypoxia and cell death in the nephron epithelium, impairing essential fluid handling and waste removal functions.","alternate_descriptions":[],"data_types":["SPATIAL_TRANSCRIPTOMICS"],"data_type_labels":["Spatially resolved transcriptomics"],"data_type_label":"Spatially resolved transcriptomics","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[25],"sample_count":25,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Hospital-Acquired Acute Kidney Injury (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Hospital-Acquired_Acute_Kidney_Injury","name":"Hospital-Acquired Acute Kidney Injury","kind":"Disorder","source_path":"kb/disorders/Hospital-Acquired_Acute_Kidney_Injury.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hospital-Acquired_Acute_Kidney_Injury.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hospital-Acquired_Acute_Kidney_Injury.html#dataset-geo-gse307588"}],"context_names":["Hospital-Acquired Acute Kidney Injury"],"disease_names":["Hospital-Acquired Acute Kidney Injury"],"disease_name":"Hospital-Acquired Acute Kidney Injury","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hospital-Acquired_Acute_Kidney_Injury.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hospital-Acquired_Acute_Kidney_Injury.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hospital-Acquired_Acute_Kidney_Injury.html#dataset-geo-gse307588"]},{"id":"dataset:geo:gse307782","accession":"geo:GSE307782","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE307782","title":"PRDM16 Modulates Aspects of Cell-Cycle Dynamics and Maturation in Human iPSC-Derived Cardiomyocytes","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE307782","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE307782","reference_title":"PRDM16 Modulates Aspects of Cell-Cycle Dynamics and Maturation in Human iPSC-Derived Cardiomyocytes","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Reduced PRDM16 expression significantly impairs the metabolic and structural maturation of hiPSC-CMs, leading to dysregulated sarcomeric protein expression ratios and compromised engineered heart tissue (EHT) function.","explanation":"The repository's own summary states what the deposited experiment shows: lowering PRDM16 in human cardiomyocytes impairs maturation and contractile tissue function, which is the human-cell counterpart of the proliferation and maturation arm of the mechanism curated above."}],"notes":["siRNA knockdown and lentiviral overexpression of PRDM16 in hiPSC-derived cardiomyocytes, directly probing the proliferation-maturation axis implicated in the PRDM16 loss-of-function mechanism curated above (reduced PRDM16 impairs metabolic/structural maturation and sarcomeric protein ratios; no linked PMID at time of curation)."],"contexts":[{"id":"disorder:Left_Ventricular_Noncompaction_8","name":"Left Ventricular Noncompaction 8","kind":"Disorder","source_path":"kb/disorders/Left_Ventricular_Noncompaction_8.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Left_Ventricular_Noncompaction_8.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Left_Ventricular_Noncompaction_8.html#dataset-geo-gse307782"}],"context_names":["Left Ventricular Noncompaction 8"],"disease_names":["Left Ventricular Noncompaction 8"],"disease_name":"Left Ventricular Noncompaction 8","same_context_model_ids":["model:kb/disorders/Left_Ventricular_Noncompaction_8.yaml:H9c2 rat cardiomyoblast PRDM16 promoter-binding system","model:kb/disorders/Left_Ventricular_Noncompaction_8.yaml:PRDM16-Q187X proband-derived hiPSC-cardiomyocytes"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Left_Ventricular_Noncompaction_8.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Left_Ventricular_Noncompaction_8.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Left_Ventricular_Noncompaction_8.html#dataset-geo-gse307782"]},{"id":"dataset:geo:gse308264","accession":"geo:GSE308264","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE308264","title":"Genome-wide profiling of histone modification H3K27ac and CTCF transcription factor binding in Rett syndrome iPS cells","alternate_titles":[],"description":"Rett syndrome (RTT) is a rare neurodevelopmental disorder that primarily affects females. It is caused by mutations in the MECP2 gene located on the X chromosome, which plays a critical role in normal brain development and function. The mutation induces epigenetic changes and chromatin re-arrangement which lead to alteration to H3K27ac and CTCF binding in the genome. To determine the epigenetic changes in RTT cells, we performed ChIP-seq on healthy and Rett syndrome iPS cells. RTT increased the H3K27ac marks and reduce CTCF binding, which supports the evidence of MeCP2 role in chromatin alterations.","alternate_descriptions":[],"data_types":["CHIP_SEQ"],"data_type_labels":["Chromatin immunoprecipitation sequencing"],"data_type_label":"Chromatin immunoprecipitation sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[24],"sample_count":24,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41764479"],"publication_contexts":[{"context_id":"disorder:Rett_Syndrome","publication":"PMID:41764479"}],"publication":"PMID:41764479","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41764479","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Rett Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Rett_Syndrome","name":"Rett Syndrome","kind":"Disorder","source_path":"kb/disorders/Rett_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rett_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Rett_Syndrome.html#dataset-geo-gse308264"}],"context_names":["Rett Syndrome"],"disease_names":["Rett Syndrome"],"disease_name":"Rett Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Rett_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rett_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Rett_Syndrome.html#dataset-geo-gse308264"]},{"id":"dataset:geo:gse308369","accession":"geo:GSE308369","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE308369","title":"Ischemic stroke accelerates atherosclerosis progression via FTO-mediated epigenetic modification [RNA-Seq]","alternate_titles":[],"description":"Residual risk of stroke recurrence persists despite the administration of the prevention measures. The recurrent risk is particularly high in patients with atherosclerosis. However, the underlying mechanisms leading to atherosclerosis progression and recurrent stroke have not been fully understood. We found that stroke accelerated atherosclerosis progression.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[8],"sample_count":8,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Ischemic Stroke (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Ischemic_Stroke","name":"Ischemic Stroke","kind":"Disorder","source_path":"kb/disorders/Ischemic_Stroke.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ischemic_Stroke.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Ischemic_Stroke.html#dataset-geo-gse308369"}],"context_names":["Ischemic Stroke"],"disease_names":["Ischemic Stroke"],"disease_name":"Ischemic Stroke","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Ischemic_Stroke.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ischemic_Stroke.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Ischemic_Stroke.html#dataset-geo-gse308369"]},{"id":"dataset:geo:gse308373","accession":"geo:GSE308373","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE308373","title":"Pertussis Toxin as well as Staphylococcal superantigen induce glycolysis as the major energy source during CD4+ T cell activation in a human tonsil organoid model","alternate_titles":[],"description":"Bystander activation represents an innate-like mechanism by which T cells, particularly effector and memory subsets, can become activated in the absence of cognate antigen recognition. Using human tonsil organoid cultures as a physiologically relevant model, we investigated bystander activation of CD4+ memory T cells in situ in comparison to superantigen stimulation. Tonsillar T cells were stimulated with pertussis toxin – a component of the childhood pertussis vaccine – in comparison to TSST-1 as the staphylococcal superantigen and assessed for activation status, cytokine expression, RNA expression, and metabolic reprogramming.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[20],"sample_count":20,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Pertussis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Pertussis","name":"Pertussis","kind":"Disorder","source_path":"kb/disorders/Pertussis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pertussis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pertussis.html#dataset-geo-gse308373"}],"context_names":["Pertussis"],"disease_names":["Pertussis"],"disease_name":"Pertussis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Pertussis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pertussis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Pertussis.html#dataset-geo-gse308373"]},{"id":"dataset:geo:gse308470","accession":"geo:GSE308470","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE308470","title":"Possible association between the microbiota in subgingival and atherosclerotic plaque in patients with carotid stenosis.","alternate_titles":[],"description":"Bacterial DNA was detected in both subgingival and carotid plaque samples. The microbial composition differed between subgingival and carotid plaque communities. Alpha diversity analysis revealed significantly higher diversity in subgingival samples compared to carotid plaques (p = 0.039). Beta diversity analysis, including unweighted UniFrac analysis (p<0.001), linear discriminant analysis with effect size estimation, cladogram-based analysis, and principal component analysis, confirmed marked differences between the subgingival and carotid plaque microbiota. However, the study did reveal overlaps in a few individual cases.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[50],"sample_count":50,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41908294"],"publication_contexts":[{"context_id":"disorder:Carotid_Stenosis","publication":"PMID:41908294"}],"publication":"PMID:41908294","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41908294","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Carotid Stenosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Carotid_Stenosis","name":"Carotid Stenosis","kind":"Disorder","source_path":"kb/disorders/Carotid_Stenosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Carotid_Stenosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Carotid_Stenosis.html#dataset-geo-gse308470"}],"context_names":["Carotid Stenosis"],"disease_names":["Carotid Stenosis"],"disease_name":"Carotid Stenosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Carotid_Stenosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Carotid_Stenosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Carotid_Stenosis.html#dataset-geo-gse308470"]},{"id":"dataset:geo:gse308814","accession":"geo:GSE308814","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE308814","title":"Single-cell mRNA analysis and surface marker expression profiling of circulating immune cells in human with alpha-gal syndrome","alternate_titles":[],"description":"Alpha-gal syndrome (AGS) is an IgE-mediated allergy to the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal). Alpha-gal is found in the tissues of non-catarrhine mammals, and the characteristic delayed reactions are caused by the consumption of red meat, visceral organs, dairy, gelatin, and other products, including medications sourced from non-primate mammals. The syndrome is profoundly influenced by geographic locale, reflecting the important role of tick bites in sensitization. However, the specific immune cells, their interactions, and the downstream signaling cascades triggered by tick bites are not well understood.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[43],"sample_count":43,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Alpha-gal Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Alpha-gal_Syndrome","name":"Alpha-gal Syndrome","kind":"Disorder","source_path":"kb/disorders/Alpha-gal_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alpha-gal_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Alpha-gal_Syndrome.html#dataset-geo-gse308814"}],"context_names":["Alpha-gal Syndrome"],"disease_names":["Alpha-gal Syndrome"],"disease_name":"Alpha-gal Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Alpha-gal_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alpha-gal_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Alpha-gal_Syndrome.html#dataset-geo-gse308814"]},{"id":"dataset:geo:gse308876","accession":"geo:GSE308876","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE308876","title":"Dorsal Root Ganglion-Mediated Modulation of Neuroinflammation and Neurovasodilation in Rosacea by Gabapentin","alternate_titles":[],"description":"Mouse bulk RNA-seq of skin and dorsal root ganglia from an LL-37-induced rosacea model treated with gabapentin, profiling neuroimmune and neurovascular activation (CGRP, nitric oxide synthases) and its suppression. Aligns with the TRP/neuropeptide and neurovascular vasodilation nodes.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[24],"sample_count":24,"conditions":["LL-37-induced rosacea-like mouse skin","LL-37-induced rosacea-like mouse dorsal root ganglia","gabapentin-treated skin and dorsal root ganglia"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE308876","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE308876","reference_title":"Dorsal Root Ganglion-Mediated Modulation of Neuroinflammation and Neurovasodilation in Rosacea by Gabapentin","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"LL37 triggered parallel neuroimmune and neurovascular activation in skin and DRG, including upregulating of Th2, IGF, CGRP, and nitric oxide synthases.","explanation":"GEO summary documents neuropeptide (CGRP) and nitric oxide synthase induction in the LL-37 rosacea model, the neurovascular program this entry models."}],"notes":["No linked publication is listed on the GEO record at time of curation."],"contexts":[{"id":"disorder:Rosacea","name":"Rosacea","kind":"Disorder","source_path":"kb/disorders/Rosacea.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rosacea.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Rosacea.html#dataset-geo-gse308876"}],"context_names":["Rosacea"],"disease_names":["Rosacea"],"disease_name":"Rosacea","same_context_model_ids":["model:kb/disorders/Rosacea.yaml:HaCaT keratinocytes under simulated rosacea conditions","model:kb/disorders/Rosacea.yaml:Paired lesional and non-lesional papulopustular rosacea skin explants","model:kb/disorders/Rosacea.yaml:SZ95 sebocyte and live Demodex mite co-culture"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Rosacea.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rosacea.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Rosacea.html#dataset-geo-gse308876"]},{"id":"dataset:geo:gse309126","accession":"geo:GSE309126","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE309126","title":"Branched chain amino acid sufficiency is necessary for proper luteinizing hormone response, testosterone synthesis, and motor coordination","alternate_titles":[],"description":"Bulk RNA-seq comparing freely fed Bckdk-knockout and wild-type non-growing adult male mouse skeletal muscle. The study found few transcriptomic differences and should not be interpreted as a human brain-disease dataset.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41587643"],"publication_contexts":[{"context_id":"disorder:BCKDK_Deficiency","publication":"PMID:41587643"}],"publication":"PMID:41587643","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41587643","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:41587643","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41587643","reference_title":"A metabolic basis for motor deficits in mice lacking BCKDK.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"RNA sequencing data produced in this study are available in the Gene Expression Ominbus database: accession numberGSE309126.","explanation":"The publication directly identifies the deposited RNA-seq accession."}],"notes":["Organism: Mus musculus. GEO. The publication's data-availability statement identifies accession GSE309126; analyzed tissue was skeletal muscle."],"contexts":[{"id":"disorder:BCKDK_Deficiency","name":"BCKDK Deficiency","kind":"Disorder","source_path":"kb/disorders/BCKDK_Deficiency.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/BCKDK_Deficiency.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/BCKDK_Deficiency.html#dataset-geo-gse309126"}],"context_names":["BCKDK Deficiency"],"disease_names":["BCKDK Deficiency"],"disease_name":"BCKDK Deficiency","same_context_model_ids":["model:kb/disorders/BCKDK_Deficiency.yaml:Mutant BCKDK transfection functional assay","model:kb/disorders/BCKDK_Deficiency.yaml:Patient-derived BCKDK-deficient iPSC neural progenitors and neurons"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/BCKDK_Deficiency.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/BCKDK_Deficiency.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/BCKDK_Deficiency.html#dataset-geo-gse309126"]},{"id":"dataset:geo:gse309430","accession":"geo:GSE309430","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE309430","title":"Blood-Based Gene Signatures Associated with Therapeutic Response to Anti-TNF Therapy in Rheumatoid Arthritis: A Combined Meta-Analytical and Machine Learning Approach","alternate_titles":[],"description":"Objective Tumor necrosis factor alpha (TNF-α) inhibitors have significantly improved outcomes in rheumatoid arthritis (RA); however, up to 30–40% of patients show inadequate response. This highlights the need for predictive biomarkers to guide personalized therapy. Blood transcriptome profiling is a promising strategy for identifying gene signatures linked to treatment response, though prior studies have shown inconsistent results due to technical and biological heterogeneity. Methods We performed a comprehensive meta-analysis of baseline blood transcriptome datasets from eight independent RA cohorts to identify genes consistently upregulated in patients who responded to TNF-α inhibitors.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[8],"sample_count":8,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42370093"],"publication_contexts":[{"context_id":"disorder:Rheumatoid_Arthritis","publication":"PMID:42370093"}],"publication":"PMID:42370093","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42370093","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Rheumatoid Arthritis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Rheumatoid_Arthritis","name":"Rheumatoid Arthritis","kind":"Disorder","source_path":"kb/disorders/Rheumatoid_Arthritis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rheumatoid_Arthritis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Rheumatoid_Arthritis.html#dataset-geo-gse309430"}],"context_names":["Rheumatoid Arthritis"],"disease_names":["Rheumatoid Arthritis"],"disease_name":"Rheumatoid Arthritis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Rheumatoid_Arthritis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rheumatoid_Arthritis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Rheumatoid_Arthritis.html#dataset-geo-gse309430"]},{"id":"dataset:geo:gse309535","accession":"geo:GSE309535","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE309535","title":"Transcriptional dysregulation in the spinal cord of SCA3 provides insights into disease mechanisms","alternate_titles":[],"description":"Bulk RNA-seq dataset from spinal cord of SCA3 KIQ300 and wild-type mice at 24 and 56 weeks of age, supporting analysis of early and progressive spinal cord transcriptional dysregulation in SCA3.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[{"id":"UBERON:0002240","label":"spinal cord","display_label":"spinal cord","url":"http://purl.obolibrary.org/obo/UBERON_0002240"}],"sample_type_labels":["spinal cord"],"sample_counts":[24],"sample_count":24,"conditions":["SCA3 KIQ300 mouse","wild-type mouse","24 weeks","56 weeks"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41613623"],"publication_contexts":[{"context_id":"disorder:Machado_Joseph_Disease","publication":"PMID:41613623"}],"publication":"PMID:41613623","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41613623","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:41613623","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41613623","reference_title":"Early transcriptomic perturbations highlight the spinal cord as a key pathogenic region in spinocerebellar ataxia type 3.","supports":"SUPPORT","evidence_source":null,"snippet":"Here, we present the first comprehensive analysis of the spinal cord transcriptome in SCA3 using both human and mouse model tissue.","explanation":"Supports inclusion of this dataset as a spinal-cord-focused transcriptomic resource for SCA3 mechanism and biomarker studies."}],"notes":[],"contexts":[{"id":"disorder:Machado_Joseph_Disease","name":"Machado-Joseph Disease","kind":"Disorder","source_path":"kb/disorders/Machado_Joseph_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Machado_Joseph_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Machado-Joseph_Disease.html#dataset-geo-gse309535"}],"context_names":["Machado-Joseph Disease"],"disease_names":["Machado-Joseph Disease"],"disease_name":"Machado-Joseph Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Machado_Joseph_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Machado_Joseph_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Machado-Joseph_Disease.html#dataset-geo-gse309535"]},{"id":"dataset:geo:gse309563","accession":"geo:GSE309563","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE309563","title":"Differences in miRNAs profile in pregnant women with preeclampsia compared with healthy pregnant women","alternate_titles":[],"description":"Individualized outcome prediction classifiers were successfully constructed through expression profiling of a total of 800 human miRNAs in serum samples of 12 pregnant women (4 samples from severe preeclampsia pregnancies, 4 samples from mild preeclampsia pregnancies and 4 samples from healthy pregnancies)","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42135755"],"publication_contexts":[{"context_id":"disorder:Preeclampsia","publication":"PMID:42135755"}],"publication":"PMID:42135755","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42135755","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Preeclampsia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Preeclampsia","name":"Preeclampsia","kind":"Disorder","source_path":"kb/disorders/Preeclampsia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Preeclampsia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Preeclampsia.html#dataset-geo-gse309563"}],"context_names":["Preeclampsia"],"disease_names":["Preeclampsia"],"disease_name":"Preeclampsia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Preeclampsia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Preeclampsia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Preeclampsia.html#dataset-geo-gse309563"]},{"id":"dataset:geo:gse309906","accession":"geo:GSE309906","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE309906","title":"Single-cell RNA sequencing of stem cell–like memory T (Tscm) cells from rheumatoid arthritis patients and healthy controls","alternate_titles":[],"description":"Stem cell–like memory T (Tscm) cells are a subset of T cells with self-renewal capacity and multipotent differentiation potential upon antigen stimulation. Tscm cells have been implicated in the pathogenesis of autoimmune diseases. In this study, we performed single-cell RNA sequencing using the 10x Genomics platform on Tscm cells enriched by fluorescence-activated cell sorting (FACS). Our objective was to characterize the transcriptomic signatures of Tscm cells in patients with rheumatoid arthritis (RA) and to identify disease-specific features that may contribute to RA pathogenesis and progression.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[11],"sample_count":11,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42309459"],"publication_contexts":[{"context_id":"disorder:Rheumatoid_Arthritis","publication":"PMID:42309459"}],"publication":"PMID:42309459","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42309459","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Rheumatoid Arthritis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Rheumatoid_Arthritis","name":"Rheumatoid Arthritis","kind":"Disorder","source_path":"kb/disorders/Rheumatoid_Arthritis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rheumatoid_Arthritis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Rheumatoid_Arthritis.html#dataset-geo-gse309906"}],"context_names":["Rheumatoid Arthritis"],"disease_names":["Rheumatoid Arthritis"],"disease_name":"Rheumatoid Arthritis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Rheumatoid_Arthritis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rheumatoid_Arthritis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Rheumatoid_Arthritis.html#dataset-geo-gse309906"]},{"id":"dataset:geo:gse310073","accession":"geo:GSE310073","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE310073","title":"Immunotolerant Oligomer Scaffolds Promote Regenerative Remodeling and Improved Muscle Structure and Function After Volumetric Muscle Loss","alternate_titles":[],"description":"Volumetric muscle loss (VML) overwhelms endogenous repair mechanisms, leading to defect contraction, fibrosis, and persistent aesthetic and functional deficits. Restorative biomaterials capable of re-establishing muscle structure and function represent promising strategies for treating severe injuries where conventional surgical repair is inadequate. Using a rat full-thickness VML model, we evaluated Oligomer, an engineered collagen polymeric biomaterial through spatial transcriptomic profiling.","alternate_descriptions":[],"data_types":["SPATIAL_TRANSCRIPTOMICS"],"data_type_labels":["Spatially resolved transcriptomics"],"data_type_label":"Spatially resolved transcriptomics","organisms":[{"id":"NCBITaxon:10116","label":"Rattus norvegicus","display_label":"rat","url":"http://purl.obolibrary.org/obo/NCBITaxon_10116"}],"organism_labels":["Rattus norvegicus"],"organism_label":"Rattus norvegicus","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41796221"],"publication_contexts":[{"context_id":"disorder:Volumetric_Muscle_Loss","publication":"PMID:41796221"}],"publication":"PMID:41796221","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41796221","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Volumetric Muscle Loss (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Volumetric_Muscle_Loss","name":"Volumetric Muscle Loss","kind":"Disorder","source_path":"kb/disorders/Volumetric_Muscle_Loss.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Volumetric_Muscle_Loss.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Volumetric_Muscle_Loss.html#dataset-geo-gse310073"}],"context_names":["Volumetric Muscle Loss"],"disease_names":["Volumetric Muscle Loss"],"disease_name":"Volumetric Muscle Loss","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Volumetric_Muscle_Loss.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Volumetric_Muscle_Loss.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Volumetric_Muscle_Loss.html#dataset-geo-gse310073"]},{"id":"dataset:geo:gse310095","accession":"geo:GSE310095","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE310095","title":"Whole Blood Transcriptomics Differentiates Circulating Gene Expression Between Coronary Artery Disease and Peripheral Artery Disease","alternate_titles":[],"description":"Coronary artery disease (CAD) and peripheral artery disease (PAD) are prevalent atherosclerotic disorders that exhibit distinct clinical and pathological presentations. We used whole-blood RNA sequencing to investigate circulating transcriptomic differences between PAD and CAD. Whole-blood RNA sequencing was performed in 71 subjects 40-65 years of age with symptomatic PAD (n=20) or CAD (n=51). Patients with concomitant PAD and CAD were excluded. Differential expression analysis was performed to compare circulating gene expression in patients with PAD and patients with CAD. We identified 106 genes differentially expressed between PAD and CAD (p adj. < 0.1).","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[71],"sample_count":71,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41661212"],"publication_contexts":[{"context_id":"disorder:Coronary_Artery_Disease","publication":"PMID:41661212"},{"context_id":"disorder:Peripheral_Artery_Disease","publication":"PMID:41661212"}],"publication":"PMID:41661212","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41661212","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Coronary Artery Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values.","Identified by GEO DataSets index search for Peripheral Artery Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Coronary_Artery_Disease","name":"Coronary Artery Disease","kind":"Disorder","source_path":"kb/disorders/Coronary_Artery_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Coronary_Artery_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Coronary_Artery_Disease.html#dataset-geo-gse310095"},{"id":"disorder:Peripheral_Artery_Disease","name":"Peripheral Artery Disease","kind":"Disorder","source_path":"kb/disorders/Peripheral_Artery_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Peripheral_Artery_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Peripheral_Artery_Disease.html#dataset-geo-gse310095"}],"context_names":["Coronary Artery Disease","Peripheral Artery Disease"],"disease_names":["Coronary Artery Disease","Peripheral Artery Disease"],"disease_name":"Coronary Artery Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Coronary_Artery_Disease.yaml","kb/disorders/Peripheral_Artery_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Coronary_Artery_Disease.yaml","https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Peripheral_Artery_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Coronary_Artery_Disease.html#dataset-geo-gse310095","https://dismech.monarchinitiative.org/pages/disorders/Peripheral_Artery_Disease.html#dataset-geo-gse310095"]},{"id":"dataset:geo:gse31014","accession":"geo:GSE31014","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE31014","title":"Identification of Gene Networks and Pathways Associated with Guillain-Barre Syndrome","alternate_titles":[],"description":"The underlying change of gene network expression of Guillain-Barre syndrome (GBS) remains elusive. We sought to identify GBS-associated gene networks and signalling pathways by analyzing the transcriptional profile of leukocytes in the patients with GBS.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[14],"sample_count":14,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:22253732"],"publication_contexts":[{"context_id":"disorder:Guillain_Barre_Syndrome","publication":"PMID:22253732"}],"publication":"PMID:22253732","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/22253732","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Guillain-Barre Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Guillain_Barre_Syndrome","name":"Guillain-Barre Syndrome","kind":"Disorder","source_path":"kb/disorders/Guillain_Barre_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Guillain_Barre_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Guillain-Barre_Syndrome.html#dataset-geo-gse31014"}],"context_names":["Guillain-Barre Syndrome"],"disease_names":["Guillain-Barre Syndrome"],"disease_name":"Guillain-Barre Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Guillain_Barre_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Guillain_Barre_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Guillain-Barre_Syndrome.html#dataset-geo-gse31014"]},{"id":"dataset:geo:gse310241","accession":"geo:GSE310241","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE310241","title":"Mucosal inflammation and pre-existing antibodies define protection and disease outcomes in human Bordetella pertussis challenge","alternate_titles":[],"description":"Whooping cough, caused by Bordetella pertussis (BP), persists despite widespread vaccination with acellular pertussis (aP) vaccines, which protect against disease but provide incomplete and short-lived immunity against infection and transmission. To define correlates of protection and mechanisms underlying symptom development, we characterized systemic and mucosal immune responses in a North American BP-controlled human infection model (CHIM). Healthy adults, primed in infancy with either whole-cell or aP vaccines, were intranasally challenged with escalating BP doses and classified as symptomatic, asymptomatic, or non-infected.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[414],"sample_count":414,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42465938"],"publication_contexts":[{"context_id":"disorder:Pertussis","publication":"PMID:42465938"}],"publication":"PMID:42465938","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42465938","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Pertussis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Pertussis","name":"Pertussis","kind":"Disorder","source_path":"kb/disorders/Pertussis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pertussis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pertussis.html#dataset-geo-gse310241"}],"context_names":["Pertussis"],"disease_names":["Pertussis"],"disease_name":"Pertussis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Pertussis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pertussis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Pertussis.html#dataset-geo-gse310241"]},{"id":"dataset:geo:gse310327","accession":"geo:GSE310327","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE310327","title":"Microdystrophins Partially Rescue Duchenne Muscular Dystrophy Deficits in iPSC-Cardiomyocytes","alternate_titles":[],"description":"Duchenne muscular dystrophy (DMD) is a severe muscle wasting disease caused by the lack of dystrophin. Dilated cardiomyopathy is the leading cause of death in DMD patients. Smaller variants of dystrophin, called microdystrophins, amenable to packaging into adeno-associated virus (AAV), have shown to be effective in improving skeletal muscle function in animal models; however, the functional benefit of these microdystrophins in the DMD heart remains unclear. To determine the efficacy of microdystrophin gene therapy, we compared three microdystrophin variants in DMD cardiomyocytes differentiated from human induced pluripotent stem cells (iPSCs).","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[34],"sample_count":34,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Duchenne Muscular Dystrophy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Duchenne_Muscular_Dystrophy","name":"Duchenne Muscular Dystrophy","kind":"Disorder","source_path":"kb/disorders/Duchenne_Muscular_Dystrophy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Duchenne_Muscular_Dystrophy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Duchenne_Muscular_Dystrophy.html#dataset-geo-gse310327"}],"context_names":["Duchenne Muscular Dystrophy"],"disease_names":["Duchenne Muscular Dystrophy"],"disease_name":"Duchenne Muscular Dystrophy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Duchenne_Muscular_Dystrophy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Duchenne_Muscular_Dystrophy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Duchenne_Muscular_Dystrophy.html#dataset-geo-gse310327"]},{"id":"dataset:geo:gse310367","accession":"geo:GSE310367","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE310367","title":"Brain Molecular Mechanisms in Rasmussen Encephalitis","alternate_titles":[],"description":"Objective: Identify molecular mechanisms in brain tissue of Rasmussen encephalitis (RE) when compared to people with non-RE epilepsy (PWE) and control cases using whole exome sequencing (WES), RNAseq, and proteomics. Methods: Frozen brain tissue (ages 2-19 years) was obtained from control autopsy (n=14), surgical PWE (n=10), and surgical RE cases (n=27). We evaluated WES variants in RE associated with epilepsy, seizures, RE, and human leukocyte antigens (HLAs). Differential expression was evaluated by RNAseq (adjusted p<0.05) and label-free quantitative mass spectrometry (false discovery rate<5%) in the three groups.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[49],"sample_count":49,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:36336987"],"publication_contexts":[{"context_id":"disorder:Rasmussen_Encephalitis","publication":"PMID:36336987"}],"publication":"PMID:36336987","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36336987","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Rasmussen Encephalitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Rasmussen_Encephalitis","name":"Rasmussen Encephalitis","kind":"Disorder","source_path":"kb/disorders/Rasmussen_Encephalitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rasmussen_Encephalitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Rasmussen_Encephalitis.html#dataset-geo-gse310367"}],"context_names":["Rasmussen Encephalitis"],"disease_names":["Rasmussen Encephalitis"],"disease_name":"Rasmussen Encephalitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Rasmussen_Encephalitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rasmussen_Encephalitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Rasmussen_Encephalitis.html#dataset-geo-gse310367"]},{"id":"dataset:geo:gse310627","accession":"geo:GSE310627","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE310627","title":"Menstrual Fluid-Derived Small Extracellular Vesicles: A Novel Reservoir with Distinct Molecular Signatures and Implications for Endometriosis Etiopathology","alternate_titles":[],"description":"STUDY QUESTION: Can the transcriptomic profile of small extracellular vesicles (sEV) derived from menstrual fluid (MF) provide insight into their potential roles as biomarkers and mediators in endometriosis (EM) development? SUMMARY ANSWER: MF-derived sEV from EM patients display altered molecular signatures reflective of EM pathophysiology and exhibit enhanced proangiogenic activity in vitro. WHAT IS KNOWN ALREADY: EM is a chronic gynecological disorder affecting approximately 10% of reproductive-age women, associated with pain, infertility, and delayed diagnosis.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41924633"],"publication_contexts":[{"context_id":"disorder:Endometriosis","publication":"PMID:41924633"}],"publication":"PMID:41924633","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41924633","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Endometriosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Endometriosis","name":"Endometriosis","kind":"Disorder","source_path":"kb/disorders/Endometriosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Endometriosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Endometriosis.html#dataset-geo-gse310627"}],"context_names":["Endometriosis"],"disease_names":["Endometriosis"],"disease_name":"Endometriosis","same_context_model_ids":["model:kb/disorders/Endometriosis.yaml:Droplet-based microfluidic protease-activity profiling platform (PrAMA; MIT Griffith/Han)"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Endometriosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Endometriosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Endometriosis.html#dataset-geo-gse310627"]},{"id":"dataset:geo:gse310700","accession":"geo:GSE310700","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE310700","title":"Transcriptomic analysis of STUB1 knockdown in HEK293 cells under normal and heat-shock conditions","alternate_titles":[],"description":"RNA-seq of HEK293 cells carrying shRNA against STUB1 versus non-targeting control, under basal conditions and after acute heat shock. This is a knockdown cell-line experiment, not SCAR16 patient material, and the submitters generated it for a study of the dominant allelic disorder SCA48. It is included for its direct perturbation of STUB1 in the heat-shock response, the axis addressed in the HUMAN_MODEL_MISMATCH discussion.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42567515"],"publication_contexts":[{"context_id":"disorder:Spinocerebellar_Ataxia_48","publication":"PMID:42567515"}],"publication":"PMID:42567515","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42567515","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE310700","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE310700","reference_title":"Transcriptomic analysis of STUB1 knockdown in HEK293 cells under normal and heat-shock conditions","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"to investigate the role of the STUB1/CHIP co-chaperone/E3 ligase in the cellular heat-shock response and proteostasis","explanation":"The repository's own summary states the dataset's purpose, which is what makes it relevant to the proteostasis node here."}],"notes":["Dataset relevance triage. `just discover-datasets` returned twelve candidates and eleven were rejected. The three scored DIRECT are mouse studies of TDP2 and SNX14, matched only on the words \"autosomal recessive spinocerebellar ataxia\" in their summaries; they are different recessive ataxias and are the Named Entity Confusion case the curation guide warns about. The GENE_ONLY hits are STUB1 in tumour immunology, prostate cancer and epithelial NF-kB signalling, none of which bear on cerebellar degeneration. No SCAR16 patient-derived omics dataset was found in GEO.","RNA-seq of STUB1 knockdown under normal and heat-shock conditions, the CHIP-insufficiency model reported in the SCA48 domain-uncoupling study (PMID:42567515). It is a HEK293 cell system, not a neuronal or patient one, so it speaks to the transcriptional consequences of reduced CHIP dosage rather than to Purkinje cell biology. No patient-derived SCA48 transcriptomic, proteomic or single-cell dataset was found."],"contexts":[{"id":"disorder:Autosomal_Recessive_Spinocerebellar_Ataxia_16","name":"Autosomal Recessive Spinocerebellar Ataxia 16","kind":"Disorder","source_path":"kb/disorders/Autosomal_Recessive_Spinocerebellar_Ataxia_16.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autosomal_Recessive_Spinocerebellar_Ataxia_16.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Recessive_Spinocerebellar_Ataxia_16.html#dataset-geo-gse310700"},{"id":"disorder:Spinocerebellar_Ataxia_48","name":"Spinocerebellar Ataxia 48","kind":"Disorder","source_path":"kb/disorders/Spinocerebellar_Ataxia_48.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Spinocerebellar_Ataxia_48.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Spinocerebellar_Ataxia_48.html#dataset-geo-gse310700"}],"context_names":["Autosomal Recessive Spinocerebellar Ataxia 16","Spinocerebellar Ataxia 48"],"disease_names":["Autosomal Recessive Spinocerebellar Ataxia 16","Spinocerebellar Ataxia 48"],"disease_name":"Autosomal Recessive Spinocerebellar Ataxia 16","same_context_model_ids":["model:kb/disorders/Autosomal_Recessive_Spinocerebellar_Ataxia_16.yaml:CARP-dependent CHIP sequestration in HEK293T and N2A cells","model:kb/disorders/Autosomal_Recessive_Spinocerebellar_Ataxia_16.yaml:CHIP-perturbed U2OS Parkin mitophagy reporter cells","model:kb/disorders/Autosomal_Recessive_Spinocerebellar_Ataxia_16.yaml:HEK293 CHIP-Fbx2 NR2A-turnover reconstitution","model:kb/disorders/Autosomal_Recessive_Spinocerebellar_Ataxia_16.yaml:HEK293T CHIP-PDE9A ubiquitination and turnover assays","model:kb/disorders/Autosomal_Recessive_Spinocerebellar_Ataxia_16.yaml:Recombinant CHIP disease-variant biochemistry","model:kb/disorders/Autosomal_Recessive_Spinocerebellar_Ataxia_16.yaml:SCAR16 AX71 and AX29 fibroblast PKA-signaling assays","model:kb/disorders/Autosomal_Recessive_Spinocerebellar_Ataxia_16.yaml:SCAR16 AX71 fibroblast cilium-resorption assay","model:kb/disorders/Autosomal_Recessive_Spinocerebellar_Ataxia_16.yaml:SCAR16 p.Met211Ile/p.Glu238Ter patient fibroblasts under proteasome stress","model:kb/disorders/Autosomal_Recessive_Spinocerebellar_Ataxia_16.yaml:SCAR16 patient iPSC-derived cortical neurons","model:kb/disorders/Autosomal_Recessive_Spinocerebellar_Ataxia_16.yaml:SCAR16 patient primary fibroblasts","model:kb/disorders/Autosomal_Recessive_Spinocerebellar_Ataxia_16.yaml:STUB1 truncation constructs in SH-SY5Y and HEK293T cells","model:kb/disorders/Autosomal_Recessive_Spinocerebellar_Ataxia_16.yaml:Temperature-dependent CHIP missense-variant assays"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Autosomal_Recessive_Spinocerebellar_Ataxia_16.yaml","kb/disorders/Spinocerebellar_Ataxia_48.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autosomal_Recessive_Spinocerebellar_Ataxia_16.yaml","https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Spinocerebellar_Ataxia_48.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Recessive_Spinocerebellar_Ataxia_16.html#dataset-geo-gse310700","https://dismech.monarchinitiative.org/pages/disorders/Spinocerebellar_Ataxia_48.html#dataset-geo-gse310700"]},{"id":"dataset:geo:gse310754","accession":"geo:GSE310754","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE310754","title":"DNA methylation changes in PBMCs of multiple sclerosis patients on glatiramer acetate therapy","alternate_titles":[],"description":"DNA methylation is a universal epigenetic mechanism involved in the regulation of gene expression in both normal physiological conditions and various pathologies. It has been demonstrated that the development of multiple sclerosis (MS) is accompanied by significant alterations in DNA methylation profiles in the blood immune cells of patients. Studies investigating genome-wide DNA methylation changes during therapy for MS patients using immunomodulatory drugs are limited, and for glatiramer acetate (GA), such investigations have not been conducted at all.","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42196591"],"publication_contexts":[{"context_id":"disorder:Multiple_Sclerosis","publication":"PMID:42196591"}],"publication":"PMID:42196591","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42196591","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Multiple Sclerosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Multiple_Sclerosis","name":"Multiple Sclerosis","kind":"Disorder","source_path":"kb/disorders/Multiple_Sclerosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Multiple_Sclerosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Multiple_Sclerosis.html#dataset-geo-gse310754"}],"context_names":["Multiple Sclerosis"],"disease_names":["Multiple Sclerosis"],"disease_name":"Multiple Sclerosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Multiple_Sclerosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Multiple_Sclerosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Multiple_Sclerosis.html#dataset-geo-gse310754"]},{"id":"dataset:geo:gse311084","accession":"geo:GSE311084","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE311084","title":"Single-cell RNA sequencing reveals chondrocyte heterogeneity and fibrocartilage transition in osteonecrosis of the femoral head","alternate_titles":[],"description":"This study investigates the role of chondrocyte heterogeneity in osteonecrosis of the femoral head (ONFH) through single-cell RNA sequencing of 50,851 chondrocytes from 10 ONFH patients and 10 controls.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Osteonecrosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Osteonecrosis","name":"Osteonecrosis","kind":"Disorder","source_path":"kb/disorders/Osteonecrosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Osteonecrosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Osteonecrosis.html#dataset-geo-gse311084"}],"context_names":["Osteonecrosis"],"disease_names":["Osteonecrosis"],"disease_name":"Osteonecrosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Osteonecrosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Osteonecrosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Osteonecrosis.html#dataset-geo-gse311084"]},{"id":"dataset:geo:gse3112","accession":"geo:GSE3112","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE3112","title":"Plasma Cells in Muscle in Inclusion Body Myositis and Polymyositis","alternate_titles":[],"description":"Microarray data from muscle biopsy specimens from subjects with inclusion body myositis, polymyositis, and normals Keywords: Research study","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[40],"sample_count":40,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:16344523"],"publication_contexts":[{"context_id":"disorder:Inclusion_Body_Myositis","publication":"PMID:16344523"},{"context_id":"disorder:Polymyositis","publication":"PMID:16344523"}],"publication":"PMID:16344523","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/16344523","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Inclusion Body Myositis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.","Identified by GEO DataSets index search for Polymyositis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Inclusion_Body_Myositis","name":"Inclusion Body Myositis","kind":"Disorder","source_path":"kb/disorders/Inclusion_Body_Myositis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Inclusion_Body_Myositis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Inclusion_Body_Myositis.html#dataset-geo-gse3112"},{"id":"disorder:Polymyositis","name":"Polymyositis","kind":"Disorder","source_path":"kb/disorders/Polymyositis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Polymyositis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Polymyositis.html#dataset-geo-gse3112"}],"context_names":["Inclusion Body Myositis","Polymyositis"],"disease_names":["Inclusion Body Myositis","Polymyositis"],"disease_name":"Inclusion Body Myositis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Inclusion_Body_Myositis.yaml","kb/disorders/Polymyositis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Inclusion_Body_Myositis.yaml","https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Polymyositis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Inclusion_Body_Myositis.html#dataset-geo-gse3112","https://dismech.monarchinitiative.org/pages/disorders/Polymyositis.html#dataset-geo-gse3112"]},{"id":"dataset:geo:gse311205","accession":"geo:GSE311205","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE311205","title":"Comparative transcriptome analyses highlight distinct pathogenetic mechanisms for pleuropulmonary blastoma and congenital pulmonary airway malformations I","alternate_titles":[],"description":"Pleuropulmonary blastoma (PPB) and congenital pulmonary airway malformations (CPAM) are two rare cystic lung diseases occurring in childhood. PPB can evolve from a low-grade epithelial cyst lesion to a high-grade sarcoma with poor prognosis, while CPAM usually has a favorable non-tumorous outcome. Clinical similarities complicate diagnosis and may delay appropriate care. PPB is associated with DICER1 mutations that disturb miRNA biogenesis, altering the miRNA repertoire. Conversely, KRAS mutations are detected in CPAM, but their implication remains unclear.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Congenital Pulmonary Airway Malformation (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Congenital_Pulmonary_Airway_Malformation","name":"Congenital Pulmonary Airway Malformation","kind":"Disorder","source_path":"kb/disorders/Congenital_Pulmonary_Airway_Malformation.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Congenital_Pulmonary_Airway_Malformation.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Congenital_Pulmonary_Airway_Malformation.html#dataset-geo-gse311205"}],"context_names":["Congenital Pulmonary Airway Malformation"],"disease_names":["Congenital Pulmonary Airway Malformation"],"disease_name":"Congenital Pulmonary Airway Malformation","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Congenital_Pulmonary_Airway_Malformation.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Congenital_Pulmonary_Airway_Malformation.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Congenital_Pulmonary_Airway_Malformation.html#dataset-geo-gse311205"]},{"id":"dataset:geo:gse311535","accession":"geo:GSE311535","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE311535","title":"RNA-seq of human atherosclerotic carotid plaque tissue from diabetic patients","alternate_titles":[],"description":"Diabetes Mellitus is associated with increased risk of myocardial infarctions and strokes due to accelerated atherosclerotic plaque development and rupture. The mechanisms driving plaque rupture in the diabetic setting remain unclear. We sequenced ribosome-depleted total RNA from carotid plaques obtained from diabetic subjects undergoing carotid endarterectomy with high-grade stenosis, who either recently experienced a carotid-related ischemic cerebrovascular event (Symptomatic, n=6) or had no such event (Asymptomatic, n=6).","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41377472"],"publication_contexts":[{"context_id":"disorder:Carotid_Stenosis","publication":"PMID:41377472"}],"publication":"PMID:41377472","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41377472","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Carotid Stenosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Carotid_Stenosis","name":"Carotid Stenosis","kind":"Disorder","source_path":"kb/disorders/Carotid_Stenosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Carotid_Stenosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Carotid_Stenosis.html#dataset-geo-gse311535"}],"context_names":["Carotid Stenosis"],"disease_names":["Carotid Stenosis"],"disease_name":"Carotid Stenosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Carotid_Stenosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Carotid_Stenosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Carotid_Stenosis.html#dataset-geo-gse311535"]},{"id":"dataset:geo:gse311549","accession":"geo:GSE311549","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE311549","title":"RNA sequencing for gastric-type endocervical adenocarcinoma (GAS), usual-type endocervical adenocarcinoma (UEA), and lobular endocervical glandular hyperplasia (LEGH)","alternate_titles":[],"description":"Cervical cancer is the fourth most common malignancy among women worldwide. While the majority of cases are human papillomavirus (HPV)-associated squamous cell carcinomas, a subset consists of adenocarcinomas. Uterine cervical adenocarcinoma is further classified into gastric-type adenocarcinoma (GAS), usual-type endocervical adenocarcinoma (UEA), and other subtypes. Lobular endocervical glandular hyperplasia (LEGH), a non-neoplastic glandular lesion, has been proposed as a potential precursor of GAS. In this study, we investigated the gene expression profiles of GAS, UEA, and LEGH using RNA sequencing.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[18],"sample_count":18,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42361625"],"publication_contexts":[{"context_id":"disorder:Cervical_Adenocarcinoma","publication":"PMID:42361625"}],"publication":"PMID:42361625","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42361625","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Cervical Adenocarcinoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Cervical_Adenocarcinoma","name":"Cervical Adenocarcinoma","kind":"Disorder","source_path":"kb/disorders/Cervical_Adenocarcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cervical_Adenocarcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cervical_Adenocarcinoma.html#dataset-geo-gse311549"}],"context_names":["Cervical Adenocarcinoma"],"disease_names":["Cervical Adenocarcinoma"],"disease_name":"Cervical Adenocarcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cervical_Adenocarcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cervical_Adenocarcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cervical_Adenocarcinoma.html#dataset-geo-gse311549"]},{"id":"dataset:geo:gse311567","accession":"geo:GSE311567","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE311567","title":"Transcriptomic adaptations of human muscle in patients with polyarteritis nodosa and muscle denervation","alternate_titles":[],"description":"The molecular mechanisms that govern muscle atrophy (as seen in disuse or aging) remain incompletely defined. Through RNA-seq of human muscle, we confirm observations from mice that extensive remodeling of the neuromuscular junction (NMJ) occurs in human denervated muscle.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[13],"sample_count":13,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42019489"],"publication_contexts":[{"context_id":"disorder:Primary_Polyarteritis_Nodosa","publication":"PMID:42019489"}],"publication":"PMID:42019489","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42019489","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Primary Polyarteritis Nodosa (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Primary_Polyarteritis_Nodosa","name":"Primary Polyarteritis Nodosa","kind":"Disorder","source_path":"kb/disorders/Primary_Polyarteritis_Nodosa.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Primary_Polyarteritis_Nodosa.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Polyarteritis_Nodosa.html#dataset-geo-gse311567"}],"context_names":["Primary Polyarteritis Nodosa"],"disease_names":["Primary Polyarteritis Nodosa"],"disease_name":"Primary Polyarteritis Nodosa","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Primary_Polyarteritis_Nodosa.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Primary_Polyarteritis_Nodosa.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Primary_Polyarteritis_Nodosa.html#dataset-geo-gse311567"]},{"id":"dataset:geo:gse311858","accession":"geo:GSE311858","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE311858","title":"RUNX1 is Expressed in a Subpopulation of Dermal Fibroblasts and is Associated with Disease Severity of Systemic Sclerosis","alternate_titles":[],"description":"The activation of Runt-related transcription factor 1 (RUNX1) in fibroblasts has been implicated in wound healing and fibrosis; however, the role of RUNX1 in the fibrotic progression of the autoimmune disease systemic sclerosis (SSc) is not known. Leveraging gene expression, genome-wide DNA methylation, and single-cell resolution data of SSc skin and fibroblast, we analyzed the impact of RUNX1 dysregulation in SSc dermal fibrosis. RUNX1 function was subsequently assessed using siRNA, pharmacologic inhibition, and CRISPR knockout in 2D and 3D fibroblasts cultures.","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[16],"sample_count":16,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41381303"],"publication_contexts":[{"context_id":"disorder:Systemic_Sclerosis","publication":"PMID:41381303"}],"publication":"PMID:41381303","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41381303","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Systemic Sclerosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Systemic_Sclerosis","name":"Systemic Sclerosis","kind":"Disorder","source_path":"kb/disorders/Systemic_Sclerosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Systemic_Sclerosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Systemic_Sclerosis.html#dataset-geo-gse311858"}],"context_names":["Systemic Sclerosis"],"disease_names":["Systemic Sclerosis"],"disease_name":"Systemic Sclerosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Systemic_Sclerosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Systemic_Sclerosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Systemic_Sclerosis.html#dataset-geo-gse311858"]},{"id":"dataset:geo:gse311894","accession":"geo:GSE311894","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE311894","title":"Effects of Selenium-mediated RUNX2 Overexpression and its Transcriptome Alterations on Chondrocyte Injury in Kashin Beck disease","alternate_titles":[],"description":"RNA-seq of human chondrocytes with lentiviral RUNX2 overexpression versus controls. Note this is an engineered cell model, not patient material: the series title names the disease but the experiment manipulates RUNX2 directly.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41425094"],"publication_contexts":[{"context_id":"disorder:Kashin-Beck_Disease","publication":"PMID:41425094"}],"publication":"PMID:41425094","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41425094","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE311894","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE311894","reference_title":"Effects of Selenium-mediated RUNX2 Overexpression and its Transcriptome Alterations on Chondrocyte Injury in Kashin Beck disease","supports":"SUPPORT","evidence_source":"OTHER","snippet":"we established a RUNX2 overexpression model using lentiviral transfection in human chondrocytes.","explanation":"What the experiment actually is, quoted so the caveat in `notes` below is checkable from the record rather than taken on trust. Graded OTHER as a repository record."},{"reference":"GEO:GSE311894","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE311894","reference_title":"Effects of Selenium-mediated RUNX2 Overexpression and its Transcriptome Alterations on Chondrocyte Injury in Kashin Beck disease","supports":"NO_EVIDENCE","evidence_source":"OTHER","snippet":"These results provide a comprehensive transcriptomic resource for understanding RUNX2-mediated signaling in cartilage degeneration and may contribute to elucidating the molecular pathogenesis of osteoarthropathy such as Kashin-Beck disease.","explanation":"Graded NO_EVIDENCE deliberately. This is the sentence that connects the series to the disease, and it claims only that the data \"may contribute to elucidating\" the pathogenesis of osteoarthropathy \"such as\" Kashin-Beck disease - a resource claim, not a finding about this disease. Recording it as NO_EVIDENCE is why the series carries no pathophysiology node."}],"notes":["Listed as a resource, not as support for a claim. The entry curates no RUNX2 pathophysiology node: the series is a lentiviral overexpression model in cultured chondrocytes whose connection to the disease is the authors' own inference, and this entry does not quote the accompanying paper."],"contexts":[{"id":"disorder:Kashin-Beck_Disease","name":"Kashin-Beck Disease","kind":"Disorder","source_path":"kb/disorders/Kashin-Beck_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Kashin-Beck_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Kashin-Beck_Disease.html#dataset-geo-gse311894"}],"context_names":["Kashin-Beck Disease"],"disease_names":["Kashin-Beck Disease"],"disease_name":"Kashin-Beck Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Kashin-Beck_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Kashin-Beck_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Kashin-Beck_Disease.html#dataset-geo-gse311894"]},{"id":"dataset:geo:gse312063","accession":"geo:GSE312063","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE312063","title":"Characterization of esophageal squamous cell carcinoma cell lines sensitivity to Palbociclib","alternate_titles":[],"description":"Background: Esophageal squamous cell carcinoma (eSCC) is a highly aggressive malignancy with poor prognosis and limited therapeutic options. Although immune checkpoint inhibitors such as nivolumab, have shown clinical benefit, particularly in patients with high PD-L1 expression, this subgroup represents only a small fraction of eSCC cases. CDK4/6 inhibitors such as palbociclib have only been tested as second-line agents in eSCC, often in combination with EGFR inhibitors, with minimal benefit. Methods: Our study evaluates palbociclib as a first-line therapy in treatment-naive eSCC models. Using a panel of 22 eSCC cell lines with integrated multi-omics and phenotypic assays.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[88],"sample_count":88,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42215475"],"publication_contexts":[{"context_id":"disorder:Esophageal_Carcinoma","publication":"PMID:42215475"}],"publication":"PMID:42215475","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42215475","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Esophageal Carcinoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Esophageal_Carcinoma","name":"Esophageal Carcinoma","kind":"Disorder","source_path":"kb/disorders/Esophageal_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Esophageal_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Esophageal_Carcinoma.html#dataset-geo-gse312063"}],"context_names":["Esophageal Carcinoma"],"disease_names":["Esophageal Carcinoma"],"disease_name":"Esophageal Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Esophageal_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Esophageal_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Esophageal_Carcinoma.html#dataset-geo-gse312063"]},{"id":"dataset:geo:gse31210","accession":"geo:GSE31210","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE31210","title":"Gene expression data for pathological stage I-II lung adenocarcinomas","alternate_titles":[],"description":"Microarray profiling of 226 primary lung adenocarcinomas for expression signatures associated with clinical features.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0002048","label":"lung","display_label":"lung","url":"http://purl.obolibrary.org/obo/UBERON_0002048"}],"sample_type_labels":["lung"],"sample_counts":[226],"sample_count":226,"conditions":["lung adenocarcinoma"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Large lung adenocarcinoma cohort frequently used for expression-based stratification."],"contexts":[{"id":"disorder:Lung_Carcinoma","name":"Lung Carcinoma","kind":"Disorder","source_path":"kb/disorders/Lung_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Lung_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Lung_Carcinoma.html#dataset-geo-gse31210"}],"context_names":["Lung Carcinoma"],"disease_names":["Lung Carcinoma"],"disease_name":"Lung Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Lung_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Lung_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Lung_Carcinoma.html#dataset-geo-gse31210"]},{"id":"dataset:geo:gse312224","accession":"geo:GSE312224","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE312224","title":"Single-cell RNA-seq of endothelial and pericyte populations in the mouse cochlear stria vascularis","alternate_titles":[],"description":"Single-cell RNA sequencing characterizing transcriptional heterogeneity of endothelial cells and pericytes in the cochlear stria vascularis using Tie2-GFP and NG2-DsRed reporter mice. Relevant to understanding blood-labyrinth barrier biology and its disruption during labyrinthitis, a key pathophysiological mechanism involving pericyte and endothelial dysfunction.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[{"id":"CL:0000115","label":"endothelial cell","display_label":"endothelial cell","url":"http://purl.obolibrary.org/obo/CL_0000115"},{"id":"CL:0000669","label":"pericyte","display_label":"pericyte","url":"http://purl.obolibrary.org/obo/CL_0000669"}],"sample_type_labels":["endothelial cell","pericyte"],"sample_counts":[],"sample_count":null,"conditions":["Blood-labyrinth barrier","Stria vascularis"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":[],"contexts":[{"id":"disorder:Labyrinthitis","name":"Labyrinthitis","kind":"Disorder","source_path":"kb/disorders/Labyrinthitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Labyrinthitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Labyrinthitis.html#dataset-geo-gse312224"}],"context_names":["Labyrinthitis"],"disease_names":["Labyrinthitis"],"disease_name":"Labyrinthitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Labyrinthitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Labyrinthitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Labyrinthitis.html#dataset-geo-gse312224"]},{"id":"dataset:geo:gse312561","accession":"geo:GSE312561","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE312561","title":"Peptidyl-tRNA hydrolase 2 is an essential negative regulator of peripartum cardiomyopathy with maternal heart failure (human and mouse RNA-seq)","alternate_titles":[],"description":"The peptidyl-tRNA hydrolase 2 (PTRH2, Bit-1; BIT1) gene plays a pro-survival role during development with loss of function gene mutations causing congenital infantile multisystem disease (IMNEPD). In wild-type female mice hearts, ptrh2 protein levels significantly increase during pregnancy and decrease postpartum, demonstrating a protective role in response to pregnancy-initiated cardiac stresses. Peripartum cardiomyopathy (PPCM) is due to dysregulated protective signaling in the pregnant heart. The genetic and molecular mechanisms underlying PPCM remain poorly defined with no specific therapies.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41413062"],"publication_contexts":[{"context_id":"disorder:Peripartum_Cardiomyopathy","publication":"PMID:41413062"}],"publication":"PMID:41413062","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41413062","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Peripartum Cardiomyopathy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Peripartum_Cardiomyopathy","name":"Peripartum Cardiomyopathy","kind":"Disorder","source_path":"kb/disorders/Peripartum_Cardiomyopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Peripartum_Cardiomyopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Peripartum_Cardiomyopathy.html#dataset-geo-gse312561"}],"context_names":["Peripartum Cardiomyopathy"],"disease_names":["Peripartum Cardiomyopathy"],"disease_name":"Peripartum Cardiomyopathy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Peripartum_Cardiomyopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Peripartum_Cardiomyopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Peripartum_Cardiomyopathy.html#dataset-geo-gse312561"]},{"id":"dataset:geo:gse312646","accession":"geo:GSE312646","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE312646","title":"Heat-Shock Pathway Activation by TRC-051384 Protects Spiral Ganglion Neurons from Noise-Induced Hearing Loss [Spatial Transcriptomics]","alternate_titles":[],"description":"Noise-induced hearing loss (NIHL) is a major public health problem caused by damage to cochlear hair cells, synapses, and spiral ganglion neurons (SGNs). However, effective treatments are completely lacking. We investigated cellular stress responses induced by loud noise in a mouse model of cochlear synaptopathy and tested whether selective activation of the dominant pathway identified could confer protection. RNA sequencing and spatial transcriptomics revealed that noise exposure elicited a robust but transient upregulation of endoplasmic reticulum chaperones and proteasome subunits in SGNs and supporting cells.","alternate_descriptions":[],"data_types":["SPATIAL_TRANSCRIPTOMICS"],"data_type_labels":["Spatially resolved transcriptomics"],"data_type_label":"Spatially resolved transcriptomics","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[51],"sample_count":51,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41415422"],"publication_contexts":[{"context_id":"disorder:Noise_Induced_Hearing_Loss","publication":"PMID:41415422"}],"publication":"PMID:41415422","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41415422","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Noise Induced Hearing Loss (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Noise_Induced_Hearing_Loss","name":"Noise Induced Hearing Loss","kind":"Disorder","source_path":"kb/disorders/Noise_Induced_Hearing_Loss.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Noise_Induced_Hearing_Loss.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Noise_Induced_Hearing_Loss.html#dataset-geo-gse312646"}],"context_names":["Noise Induced Hearing Loss"],"disease_names":["Noise Induced Hearing Loss"],"disease_name":"Noise Induced Hearing Loss","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Noise_Induced_Hearing_Loss.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Noise_Induced_Hearing_Loss.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Noise_Induced_Hearing_Loss.html#dataset-geo-gse312646"]},{"id":"dataset:geo:gse312730","accession":"geo:GSE312730","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE312730","title":"Simtuzumab Attenuates Loxl2-Mediated Extracellular Matrix Remodeling and Preserves Cardiac Function in LMNA Mutation-Induced Dilated Cardiomyopathy","alternate_titles":[],"description":"Background | Dilated cardiomyopathy (DCM) caused by LMNA mutations is a severe cardiac condition marked by arrhythmias, contractile dysfunction, and excessive myocardial fibrosis, which collectively impair left ventricular function and increase the risk of heart failure. While the disease has been well characterized, a lack of insight into the pathogenesis has impeded the development of therapies. Methods | Here, we employed induced pluripotent stem cells (hiPSCs) derived from a patient carrying a LMNA point mutation (c.665A>C, p.His222Pro), alongside a murine model carrying the same mutation, to investigate the functional and molecular abnormalities driving DCM.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41841259"],"publication_contexts":[{"context_id":"disorder:Dilated_Cardiomyopathy","publication":"PMID:41841259"}],"publication":"PMID:41841259","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41841259","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Dilated Cardiomyopathy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Dilated_Cardiomyopathy","name":"Dilated Cardiomyopathy","kind":"Disorder","source_path":"kb/disorders/Dilated_Cardiomyopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dilated_Cardiomyopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy.html#dataset-geo-gse312730"}],"context_names":["Dilated Cardiomyopathy"],"disease_names":["Dilated Cardiomyopathy"],"disease_name":"Dilated Cardiomyopathy","same_context_model_ids":["model:kb/disorders/Dilated_Cardiomyopathy.yaml:Patient-specific TNNT2 R173W iPSC-derived cardiomyocytes (Clinical Trials in a Dish)"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Dilated_Cardiomyopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dilated_Cardiomyopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy.html#dataset-geo-gse312730"]},{"id":"dataset:geo:gse313156","accession":"geo:GSE313156","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE313156","title":"Temporal modulation of gene expression in a controlled Schistosoma mansoni human infection model","alternate_titles":[],"description":"Background Schistosomiasis is caused by parasitic blood flukes of the genus Schistosoma. Despite ongoing mass drug administration efforts, the disease remains a major public health burden in endemic regions. A better understanding of early host responses to schistosomiasis is critical for developing effective vaccines and therapeutics. Methods We conducted a longitudinal transcriptomic study of peripheral blood samples from 30 Schistosoma-naïve volunteers participating in two controlled human infection trials with male-or female-only S. mansoni cercariae. Blood was collected at six time points over 20 weeks post-infection.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[144],"sample_count":144,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41476985"],"publication_contexts":[{"context_id":"disorder:Schistosomiasis","publication":"PMID:41476985"}],"publication":"PMID:41476985","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41476985","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Schistosomiasis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Schistosomiasis","name":"Schistosomiasis","kind":"Disorder","source_path":"kb/disorders/Schistosomiasis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Schistosomiasis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Schistosomiasis.html#dataset-geo-gse313156"}],"context_names":["Schistosomiasis"],"disease_names":["Schistosomiasis"],"disease_name":"Schistosomiasis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Schistosomiasis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Schistosomiasis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Schistosomiasis.html#dataset-geo-gse313156"]},{"id":"dataset:geo:gse31356","accession":"geo:GSE31356","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE31356","title":"Microarray expression analysis of patients Dupuytren´s contracture (DC)","alternate_titles":[],"description":"We used a high-throughput technology, DNA microarray, to screen the entire genome for the changes in gene expression in diseased tissue to characterize Dupuytren's contracture at a molecular level and find genes that are involved in development of the disease.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:22965824"],"publication_contexts":[{"context_id":"disorder:Dupuytrens_Contracture","publication":"PMID:22965824"}],"publication":"PMID:22965824","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/22965824","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Dupuytren Contracture (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Dupuytrens_Contracture","name":"Dupuytren Contracture","kind":"Disorder","source_path":"kb/disorders/Dupuytrens_Contracture.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dupuytrens_Contracture.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Dupuytren_Contracture.html#dataset-geo-gse31356"}],"context_names":["Dupuytren Contracture"],"disease_names":["Dupuytren Contracture"],"disease_name":"Dupuytren Contracture","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Dupuytrens_Contracture.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dupuytrens_Contracture.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Dupuytren_Contracture.html#dataset-geo-gse31356"]},{"id":"dataset:geo:gse313660","accession":"geo:GSE313660","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE313660","title":"Single-cell analysis of follicular fluid reveals dysregulation of ovulatory immune function in Polycystic Ovary Syndrome patients undergoing ovarian stimulation","alternate_titles":[],"description":"Polycystic ovary syndrome is the most common endocrine condition in women and anovulatory cause of female infertility. While a pro-inflammatory cytokines and leukocyte bias in systemic circulation is well-documented in PCOS, it is not known how this inflammation extends to or affects the ovary. Additionally, the relationship between ovulation and inflammation in PCOS is not well-defined. We hypothesize that the ovarian follicular immune environment in PCOS is uniquely dysregulated, and that resolving anovulation through ovulation induction is not sufficient to alleviate this dysregulation.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[16],"sample_count":16,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41766605"],"publication_contexts":[{"context_id":"disorder:Polycystic_Ovary_Syndrome","publication":"PMID:41766605"}],"publication":"PMID:41766605","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41766605","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Polycystic Ovary Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Polycystic_Ovary_Syndrome","name":"Polycystic Ovary Syndrome","kind":"Disorder","source_path":"kb/disorders/Polycystic_Ovary_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Polycystic_Ovary_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Polycystic_Ovary_Syndrome.html#dataset-geo-gse313660"}],"context_names":["Polycystic Ovary Syndrome"],"disease_names":["Polycystic Ovary Syndrome"],"disease_name":"Polycystic Ovary Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Polycystic_Ovary_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Polycystic_Ovary_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Polycystic_Ovary_Syndrome.html#dataset-geo-gse313660"]},{"id":"dataset:geo:gse313693","accession":"geo:GSE313693","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE313693","title":"Single-nuclei RNA-seq of meningioma","alternate_titles":[],"description":"Single-nuclei transcriptomic dataset used to characterize meningioma microenvironmental states and refine subtype/risk continuum analyses.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0010506","label":"meningeal dura mater","display_label":"meningioma tissue nuclei","url":"http://purl.obolibrary.org/obo/UBERON_0010506"}],"sample_type_labels":["meningeal dura mater"],"sample_counts":[26],"sample_count":26,"conditions":["meningioma","microenvironment profiling"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41663806"],"publication_contexts":[{"context_id":"disorder:Meningioma","publication":"PMID:41663806"}],"publication":"PMID:41663806","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41663806","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:41663806","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/41663806","reference_title":"A microenvironment-determined risk continuum refines subtyping in meningioma and reveals determinants of machine learning-based tumor classification.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"Here, by applying multiomic profiling and multiple lines of orthogonal computational evaluation in multiple independent datasets, we found that not only tumor cell characteristics but also incremental changes in the tumor microenvironment (TME) have impact on epigenetic meningioma classification and clinical outcome.","explanation":"Supports multiomic dataset use for microenvironment-linked meningioma classification refinement."}],"notes":["GEO metadata reports single-nuclei RNA sequencing for meningioma subtype refinement."],"contexts":[{"id":"disorder:Meningioma","name":"Meningioma","kind":"Disorder","source_path":"kb/disorders/Meningioma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Meningioma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Meningioma.html#dataset-geo-gse313693"}],"context_names":["Meningioma"],"disease_names":["Meningioma"],"disease_name":"Meningioma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Meningioma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Meningioma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Meningioma.html#dataset-geo-gse313693"]},{"id":"dataset:geo:gse314466","accession":"geo:GSE314466","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE314466","title":"Global knockout of melanoma differentiation-associated protein 5 protects mice from chronic hypoxia/SU5416-induced pulmonary hypertension","alternate_titles":[],"description":"Pulmonary arterial hypertension (PAH) is a severe disease affecting the pulmonary arteries, causing increased blood pressure due to narrowing of the pulmonary artery lumen. Aberrant proliferation of endothelial cells (ECs) and smooth muscle cells (SMCs), along with a dysregulation of the immune response, contributes to arterial remodeling. We hypothesized that the cytosolic RNA receptor melanoma differentiation-associated protein 5 (MDA5) contributes to PAH by dysregulating pulmonary vascular cell function and immune cell response. In lung tissue from control patients and PAH patients, MDA5 immunoreactivity was widely distributed throughout the pulmonary artery wall.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42030239"],"publication_contexts":[{"context_id":"disorder:Pulmonary_hypertension","publication":"PMID:42030239"}],"publication":"PMID:42030239","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42030239","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Pulmonary hypertension (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Pulmonary_hypertension","name":"Pulmonary_hypertension","kind":"Disorder","source_path":"kb/disorders/Pulmonary_hypertension.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pulmonary_hypertension.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pulmonary_hypertension.html#dataset-geo-gse314466"}],"context_names":["Pulmonary_hypertension"],"disease_names":["Pulmonary_hypertension"],"disease_name":"Pulmonary_hypertension","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Pulmonary_hypertension.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pulmonary_hypertension.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Pulmonary_hypertension.html#dataset-geo-gse314466"]},{"id":"dataset:geo:gse314583","accession":"geo:GSE314583","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE314583","title":"Toll-Like-Receptor 5 Reduces Lung Dysbiosis and Protects Against Pulmonary Fibrosis","alternate_titles":[],"description":"Idiopathic pulmonary fibrosis (IPF) is a devastating pulmonary disease with no curative treatment other than lung transplantation. IPF results from maladaptive responses to lung epithelial injury, but the underlying mechanisms remain unclear. Here, we show that deficiency in the innate immune receptor, toll-like receptor 5 (TLR5), is associated with IPF in humans and with increased susceptibility to experimental fibrosis in mice, while activation of lung epithelial TLR5 through a synthetic flagellin analog protects from experimental fibrosis. Mechanistically, epithelial TLR5 activation induces antimicrobial gene expression and ameliorates dysbiosis after lung injury.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[106],"sample_count":106,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42234773"],"publication_contexts":[{"context_id":"disorder:Idiopathic_Pulmonary_Fibrosis","publication":"PMID:42234773"}],"publication":"PMID:42234773","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42234773","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Idiopathic Pulmonary Fibrosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Idiopathic_Pulmonary_Fibrosis","name":"Idiopathic Pulmonary Fibrosis","kind":"Disorder","source_path":"kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Idiopathic_Pulmonary_Fibrosis.html#dataset-geo-gse314583"}],"context_names":["Idiopathic Pulmonary Fibrosis"],"disease_names":["Idiopathic Pulmonary Fibrosis"],"disease_name":"Idiopathic Pulmonary Fibrosis","same_context_model_ids":["model:kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml:Immune-cell-free AT2-lineage and fibroblast organoids","model:kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml:Microengineered alveolar array lung-on-chip with breathing mechanics"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Idiopathic_Pulmonary_Fibrosis.html#dataset-geo-gse314583"]},{"id":"dataset:geo:gse314612","accession":"geo:GSE314612","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE314612","title":"Synovial transcriptomic response to intra-articular 2.5% polyacrylamide hydrogel in equine experimental osteoarthritis [RNAseq_SF]","alternate_titles":[],"description":"Background - Osteoarthritis (OA) represents one of the most common conditions treated by equine practitioners. Despite this high prevalence, no approved pharmacological intervention, biological therapy, or procedure prevents or reverses progressive destruction of degenerative joints. Intra-articular injectable polyacrylamide hydrogels (iPAAG), which consist of biocompatible non-degradable synthetic polymers, have been introduced with reported clinical efficacy. However, their potential mechanisms of action have not been fully investigated.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[93],"sample_count":93,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Osteoarthritis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. GEO reports Equus caballus; the organism is retained here as source text because this record has no ontology-mapped organism field."],"contexts":[{"id":"disorder:Osteoarthritis","name":"Osteoarthritis","kind":"Disorder","source_path":"kb/disorders/Osteoarthritis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Osteoarthritis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Osteoarthritis.html#dataset-geo-gse314612"}],"context_names":["Osteoarthritis"],"disease_names":["Osteoarthritis"],"disease_name":"Osteoarthritis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Osteoarthritis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Osteoarthritis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Osteoarthritis.html#dataset-geo-gse314612"]},{"id":"dataset:geo:gse314910","accession":"geo:GSE314910","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE314910","title":"Spatial transcriptomic signatures of cardiac sarcoidosis","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["SPATIAL_TRANSCRIPTOMICS"],"data_type_labels":["Spatially resolved transcriptomics"],"data_type_label":"Spatially resolved transcriptomics","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Cardiac_Sarcoidosis (scripts/discover_datasets.py) and verified with just verify-datasets. Cardiac sarcoidosis is named in the GEO series title. No linked publication was indexed at the time of curation."],"contexts":[{"id":"disorder:Cardiac_Sarcoidosis","name":"Cardiac Sarcoidosis","kind":"Disorder","source_path":"kb/disorders/Cardiac_Sarcoidosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cardiac_Sarcoidosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cardiac_Sarcoidosis.html#dataset-geo-gse314910"}],"context_names":["Cardiac Sarcoidosis"],"disease_names":["Cardiac Sarcoidosis"],"disease_name":"Cardiac Sarcoidosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cardiac_Sarcoidosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cardiac_Sarcoidosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cardiac_Sarcoidosis.html#dataset-geo-gse314910"]},{"id":"dataset:geo:gse314930","accession":"geo:GSE314930","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE314930","title":"Cohesin mutations suppress HLA class II gene expression to promote immune evasion during the progression to acute leukemia in children with Down syndrome [CUT&Run]","alternate_titles":[],"description":"Children with Down syndrome have a 150-fold increased risk of developing the myeloid leukemia of Down syndrome (ML-DS). ML-DS is preceded by transient abnormal myelopoiesis (TAM), which spontaneously resolves in most cases but progresses to AML with additional mutations most commonly in the cohesin complex or signaling genes. However, the mechanisms by which these alterations promote leukemia are unknown. Here, we leveraged isogenic cell lines and patient data to investigate the role of cohesin mutations in leukemia progression.","alternate_descriptions":[],"data_types":["ATAC_SEQ"],"data_type_labels":["Assay for transposase-accessible chromatin sequencing"],"data_type_label":"Assay for transposase-accessible chromatin sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[72],"sample_count":72,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Down syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Down_syndrome","name":"Down_syndrome","kind":"Disorder","source_path":"kb/disorders/Down_syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Down_syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Down_syndrome.html#dataset-geo-gse314930"}],"context_names":["Down_syndrome"],"disease_names":["Down_syndrome"],"disease_name":"Down_syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Down_syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Down_syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Down_syndrome.html#dataset-geo-gse314930"]},{"id":"dataset:geo:gse315138","accession":"geo:GSE315138","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE315138","title":"Single Cell RNA Sequencing Unveils Distinct Cellular Dynamics in Celiac Disease Duodenal Biopsies","alternate_titles":[],"description":"Celiac disease (CeD) is the most common autoimmune disorder in the U.S., affecting at least 1% of the population. The ingestion of gluten-containing proteins triggers an adaptive immune response, causing intestinal damage and leading to both gastrointestinal and systemic symptoms. Despite a strong genetic predisposition, the mechanistic understanding of CeD remains limited. The lack of approved therapy, other than dietary avoidance of gluten which is difficult and often unsuccessful, underscores the need to identify new mechanisms that can provide insights for developing therapeutics.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[8],"sample_count":8,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41642982"],"publication_contexts":[{"context_id":"disorder:Celiac_Disease","publication":"PMID:41642982"}],"publication":"PMID:41642982","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41642982","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Celiac Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Celiac_Disease","name":"Celiac Disease","kind":"Disorder","source_path":"kb/disorders/Celiac_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Celiac_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Celiac_Disease.html#dataset-geo-gse315138"}],"context_names":["Celiac Disease"],"disease_names":["Celiac Disease"],"disease_name":"Celiac Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Celiac_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Celiac_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Celiac_Disease.html#dataset-geo-gse315138"]},{"id":"dataset:geo:gse315350","accession":"geo:GSE315350","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE315350","title":"Microbiome-Derived Indole-3-lactic Acid Attenuates Cutibacterium acnes-Induced Inflammation via the Aryl Hydrocarbon Receptor Pathway","alternate_titles":[],"description":"Bulk RNA sequencing of primary human epidermal keratinocytes stimulated with C. acnes and treated with microbiome-derived tryptophan metabolites.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[18],"sample_count":18,"conditions":["C. acnes stimulation","indole-3-lactic acid treatment","indole-3-propionic acid treatment"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE315350","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE315350","reference_title":"Microbiome-Derived Indole-3-lactic Acid Attenuates Cutibacterium acnes–Induced Inflammation via the Aryl Hydrocarbon Receptor Pathway","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"In vitro, ILA and IPA significantly suppressed C. acnes-driven inflammatory mediators, including TNF-α, IL-1β, and COX2, whereas IAA demonstrated limited ef-ficacy.","explanation":"The dataset summary identifies the human keratinocyte inflammatory perturbation and transcriptional response."}],"notes":["The GEO series contains the human keratinocyte RNA-seq; a linked mouse model belongs to the associated study, not this series."],"contexts":[{"id":"disorder:Acne_Vulgaris","name":"Acne Vulgaris","kind":"Disorder","source_path":"kb/disorders/Acne_Vulgaris.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Acne_Vulgaris.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Acne_Vulgaris.html#dataset-geo-gse315350"}],"context_names":["Acne Vulgaris"],"disease_names":["Acne Vulgaris"],"disease_name":"Acne Vulgaris","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Acne_Vulgaris.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Acne_Vulgaris.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Acne_Vulgaris.html#dataset-geo-gse315350"]},{"id":"dataset:geo:gse315442","accession":"geo:GSE315442","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE315442","title":"Transcriptomic profiling reveals distinct molecular signatures among lesion types in hidradenitis suppurativa","alternate_titles":[],"description":"Bulk RNA sequencing comparing distinct HS lesion types to identify lesion-specific molecular signatures.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[48],"sample_count":48,"conditions":["HS lesional skin (multiple lesion types)","non-lesional HS skin"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":[],"contexts":[{"id":"disorder:Hidradenitis_Suppurativa","name":"Hidradenitis Suppurativa","kind":"Disorder","source_path":"kb/disorders/Hidradenitis_Suppurativa.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hidradenitis_Suppurativa.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hidradenitis_Suppurativa.html#dataset-geo-gse315442"}],"context_names":["Hidradenitis Suppurativa"],"disease_names":["Hidradenitis Suppurativa"],"disease_name":"Hidradenitis Suppurativa","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hidradenitis_Suppurativa.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hidradenitis_Suppurativa.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hidradenitis_Suppurativa.html#dataset-geo-gse315442"]},{"id":"dataset:geo:gse315862","accession":"geo:GSE315862","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE315862","title":"Targeting the Non-Homologous End-Joining Pathway Sensitizes MDM2-Amplified Liposarcoma to Doxorubicin-Induced Senescence, p53-Mediated Senescence.","alternate_titles":[],"description":"Introduction Dedifferentiated liposarcoma (DDLPS) is a rare cancer defined by amplification of MDM2 and CDK4. Conventional chemotherapy (Doxorubicin) and targeted inhibition of MDM2 and CDK4 show sporadic responses, but most tumors display primary resistance. We used an unbiased approach to identify therapeutic strategies sensitizing to these DDLPS therapies. Methods Three parallel genome-wide CRISPR-Cas9 knockout screens were conducted in DDLPS cells to sensitize to palbociclib (CDK4 inhibitor), nutlin-3a (MDM2 inhibitor) or Doxorubicin. Top screen hits were validated and characterized in both in vitro and in vivo models, while clinical data were used to corroborate molecular findings.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[36],"sample_count":36,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41811692"],"publication_contexts":[{"context_id":"disorder:Liposarcoma","publication":"PMID:41811692"}],"publication":"PMID:41811692","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41811692","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Liposarcoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Liposarcoma","name":"Liposarcoma","kind":"Disorder","source_path":"kb/disorders/Liposarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Liposarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Liposarcoma.html#dataset-geo-gse315862"}],"context_names":["Liposarcoma"],"disease_names":["Liposarcoma"],"disease_name":"Liposarcoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Liposarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Liposarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Liposarcoma.html#dataset-geo-gse315862"]},{"id":"dataset:geo:gse316062","accession":"geo:GSE316062","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE316062","title":"Chromosomal instability shapes the tumor microenvironment of esophageal adenocarcinoma via a cGAS–chemokine–myeloid axis [snRNA-Seq]","alternate_titles":[],"description":"Single-nucleus RNA-seq companion dataset from human EAC used to connect chromosomal instability to innate immune activation and myeloid-dominated microenvironmental states.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":["human esophageal adenocarcinoma tumor","CIN-high tumor microenvironment"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":[],"contexts":[{"id":"disorder:Esophageal_Adenocarcinoma","name":"Esophageal Adenocarcinoma","kind":"Disorder","source_path":"kb/disorders/Esophageal_Adenocarcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Esophageal_Adenocarcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Esophageal_Adenocarcinoma.html#dataset-geo-gse316062"}],"context_names":["Esophageal Adenocarcinoma"],"disease_names":["Esophageal Adenocarcinoma"],"disease_name":"Esophageal Adenocarcinoma","same_context_model_ids":["model:kb/disorders/Esophageal_Adenocarcinoma.yaml:Patient-derived stroma-inclusive esophageal adenocarcinoma organ chip"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Esophageal_Adenocarcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Esophageal_Adenocarcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Esophageal_Adenocarcinoma.html#dataset-geo-gse316062"]},{"id":"dataset:geo:gse316126","accession":"geo:GSE316126","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE316126","title":"Distinct immunometabolic signatures in peripheral blood mononuclear cells are linked to systemic inflammation in type 2 diabetes and diabetic kidney disease","alternate_titles":[],"description":"Diabetic kidney disease (DKD) is a frequent complication of type 2 diabetes and is closely linked to systemic inflammation. Peripheral blood mononuclear cells (PBMCs) are markers of systemic inflammatory and metabolic stress. It is unknown if metabolism-related transcriptomic alterations in these cells is associated with DKD. Using the nCounter® Human Metabolic Pathways Panel we profiled PBMC metabolic transcripts in individuals with type 2 diabetes or DKD and in controls (n = 12/group), and integrated transcriptomic data with clinical, inflammatory, and mitochondrial parameters.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[36],"sample_count":36,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Chronic Kidney Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Chronic_Kidney_Disease","name":"Chronic Kidney Disease","kind":"Disorder","source_path":"kb/disorders/Chronic_Kidney_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Kidney_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chronic_Kidney_Disease.html#dataset-geo-gse316126"}],"context_names":["Chronic Kidney Disease"],"disease_names":["Chronic Kidney Disease"],"disease_name":"Chronic Kidney Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chronic_Kidney_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Kidney_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chronic_Kidney_Disease.html#dataset-geo-gse316126"]},{"id":"dataset:geo:gse316127","accession":"geo:GSE316127","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE316127","title":"Chromosomal instability shapes the tumor microenvironment of esophageal adenocarcinoma via a cGAS-chemokine-myeloid axis","alternate_titles":[],"description":"Bulk RNA-seq dataset from engineered Barrett-derived models with graded chromosomal instability used to define CIN-linked chemokine signaling and immunosuppressive myeloid programs in esophageal adenocarcinoma.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":["TP53/CDKN2A-altered CIN model","control Barrett-derived epithelial model"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE316127","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE316127","reference_title":"Chromosomal instability shapes the tumor microenvironment of esophageal adenocarcinoma via a cGAS–chemokine–myeloid axis","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"To address this paradox, we interrogated multiple esophageal cancer models, discovering myeloid-attracting chemokines – with CXCL8 as a prominent hit – as conserved CIN-driven targets in EAC.","explanation":"Establishes the model-based finding this series reports — myeloid-attracting chemokines, CXCL8 foremost, as conserved CIN-driven targets in EAC — which is what makes it the transcriptomic evidence behind the CIN-chemokine axis."}],"notes":[],"contexts":[{"id":"disorder:Esophageal_Adenocarcinoma","name":"Esophageal Adenocarcinoma","kind":"Disorder","source_path":"kb/disorders/Esophageal_Adenocarcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Esophageal_Adenocarcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Esophageal_Adenocarcinoma.html#dataset-geo-gse316127"}],"context_names":["Esophageal Adenocarcinoma"],"disease_names":["Esophageal Adenocarcinoma"],"disease_name":"Esophageal Adenocarcinoma","same_context_model_ids":["model:kb/disorders/Esophageal_Adenocarcinoma.yaml:Patient-derived stroma-inclusive esophageal adenocarcinoma organ chip"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Esophageal_Adenocarcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Esophageal_Adenocarcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Esophageal_Adenocarcinoma.html#dataset-geo-gse316127"]},{"id":"dataset:geo:gse316316","accession":"geo:GSE316316","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE316316","title":"Association between elevated expression of GDF15/GFRAL and sarcopenia risk","alternate_titles":[],"description":"Single-cell RNA-seq addressing GDF-15/GFRAL signalling, one of the leading candidate circulating biomarkers of sarcopenia and a readout of the mitochondrial-stress arm modelled in pathophysiology#Mitochondrial Dysfunction and Oxidative Stress.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[5],"sample_count":5,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41797911"],"publication_contexts":[{"context_id":"disorder:Sarcopenia","publication":"PMID:41797911"}],"publication":"PMID:41797911","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41797911","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Mouse data; small n. Selected by manual relevance triage and accession-verified. No evidence block, as above."],"contexts":[{"id":"disorder:Sarcopenia","name":"Sarcopenia","kind":"Disorder","source_path":"kb/disorders/Sarcopenia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sarcopenia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Sarcopenia.html#dataset-geo-gse316316"}],"context_names":["Sarcopenia"],"disease_names":["Sarcopenia"],"disease_name":"Sarcopenia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Sarcopenia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sarcopenia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Sarcopenia.html#dataset-geo-gse316316"]},{"id":"dataset:geo:gse316643","accession":"geo:GSE316643","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE316643","title":"Spatial transcriptomic profiling of human heart tissue obtained from mRNA vaccine-associated myocarditis cases using GeoMx DSP","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["SPATIAL_TRANSCRIPTOMICS"],"data_type_labels":["Spatially resolved transcriptomics"],"data_type_label":"Spatially resolved transcriptomics","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[13],"sample_count":13,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41922346"],"publication_contexts":[{"context_id":"disorder:Myocarditis","publication":"PMID:41922346"}],"publication":"PMID:41922346","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41922346","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Human myocardial tissue from mRNA vaccine-associated myocarditis, profiled spatially. Directly relevant to the vaccine-associated exposure curated in the environmental section. Discovered via just discover-datasets and verified with just verify-datasets; relevance triaged manually."],"contexts":[{"id":"disorder:Myocarditis","name":"Myocarditis","kind":"Disorder","source_path":"kb/disorders/Myocarditis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myocarditis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Myocarditis.html#dataset-geo-gse316643"}],"context_names":["Myocarditis"],"disease_names":["Myocarditis"],"disease_name":"Myocarditis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Myocarditis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myocarditis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Myocarditis.html#dataset-geo-gse316643"]},{"id":"dataset:geo:gse317056","accession":"geo:GSE317056","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE317056","title":"Sex disparity in systemic sclerosis-associated pulmonary fibrosis.","alternate_titles":[],"description":"Systemic sclerosis (SSc) is a fibrotic disease with high mortality and SSc-associated pulmonary fibrosis (SSc-PF) as the leading cause of death. SSc shows a significant sex disparity with a sex ratio of 1:3 men to women, yet SSc-PF is more severe in men. This study investigates gene expression differences between men and women with SSc-PF. Whole lung tissues from healthy donors and SSc-PF patients of both sexes were analyzed by RNA sequencing. Selected genes were validated by quantitative polymerase chain reaction (qPCR) and Western blotting analyses.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[24],"sample_count":24,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42196343"],"publication_contexts":[{"context_id":"disorder:Systemic_Sclerosis","publication":"PMID:42196343"}],"publication":"PMID:42196343","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42196343","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Systemic Sclerosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Systemic_Sclerosis","name":"Systemic Sclerosis","kind":"Disorder","source_path":"kb/disorders/Systemic_Sclerosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Systemic_Sclerosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Systemic_Sclerosis.html#dataset-geo-gse317056"}],"context_names":["Systemic Sclerosis"],"disease_names":["Systemic Sclerosis"],"disease_name":"Systemic Sclerosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Systemic_Sclerosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Systemic_Sclerosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Systemic_Sclerosis.html#dataset-geo-gse317056"]},{"id":"dataset:geo:gse317746","accession":"geo:GSE317746","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE317746","title":"Mass spectrometry-based proteomic profiling of human postmortem brain tissues in tauopathies, including corticobasal degeneration, progressive supranuclear palsy, and Alzheimer’s disease","alternate_titles":[],"description":"Background: The molecular mechanisms of tauopathies, characterized by intracellular accumulation of abnormal tau encoded by MAPT, remain poorly understood. Objectives: To identify proteins associated with the primary tauopathies corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP), as well as the secondary tauopathy Alzheimer’s disease (AD), using mass spectrometry. Methods: Total homogenates were prepared from human postmortem brains of AD (n = 4), CBD (n = 4), PSP (n = 4), and their respective controls (n = 4), and analyzed by mass spectrometry.","alternate_descriptions":[],"data_types":["PROTEOMICS"],"data_type_labels":["Protein expression profiling"],"data_type_label":"Protein expression profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[16],"sample_count":16,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42254865"],"publication_contexts":[{"context_id":"disorder:Progressive_Supranuclear_Palsy","publication":"PMID:42254865"}],"publication":"PMID:42254865","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42254865","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Progressive Supranuclear Palsy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Progressive_Supranuclear_Palsy","name":"Progressive Supranuclear Palsy","kind":"Disorder","source_path":"kb/disorders/Progressive_Supranuclear_Palsy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Progressive_Supranuclear_Palsy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Progressive_Supranuclear_Palsy.html#dataset-geo-gse317746"}],"context_names":["Progressive Supranuclear Palsy"],"disease_names":["Progressive Supranuclear Palsy"],"disease_name":"Progressive Supranuclear Palsy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Progressive_Supranuclear_Palsy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Progressive_Supranuclear_Palsy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Progressive_Supranuclear_Palsy.html#dataset-geo-gse317746"]},{"id":"dataset:geo:gse318000","accession":"geo:GSE318000","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE318000","title":"Lnc-GATS-3:3/MCM7 promotes the proliferation and invasion of cervical squamous cell carcinoma cells by regulating the CDK/Rb/E2F signaling pathway","alternate_titles":[],"description":"This study investigated the role and mechanism of lnc-GATS-3:3/Mini-chromosome maintenance protein 7 (MCM7) in the proliferation, invasion, migration, and apoptosis of SiHa cervical cancer cells. Whole transcriptome sequencing was conducted on matched pairs of cervical cancer and normal tissue samples, followed by GO and KEGG enrichment analysis. The cis method was utilized to identify lncRNAs and mRNAs associated with the cell cycle. The expression levels of lnc-GATS-3:3 and MCM7 in cervical cancer and normal tissues were measured using qRT-PCR.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[8],"sample_count":8,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Cervical Squamous Cell Carcinoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Cervical_Squamous_Cell_Carcinoma","name":"Cervical Squamous Cell Carcinoma","kind":"Disorder","source_path":"kb/disorders/Cervical_Squamous_Cell_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cervical_Squamous_Cell_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cervical_Squamous_Cell_Carcinoma.html#dataset-geo-gse318000"}],"context_names":["Cervical Squamous Cell Carcinoma"],"disease_names":["Cervical Squamous Cell Carcinoma"],"disease_name":"Cervical Squamous Cell Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cervical_Squamous_Cell_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cervical_Squamous_Cell_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cervical_Squamous_Cell_Carcinoma.html#dataset-geo-gse318000"]},{"id":"dataset:geo:gse318030","accession":"geo:GSE318030","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE318030","title":"Optimized Nuclei Isolation and snRNA-seq Reveal Oligodendrocyte Pathway Dysregulation in MOGHE Brain Tissue from Pediatric Patients.","alternate_titles":[],"description":"Single-nucleus RNA sequencing of resected MOGHE brain tissue from pediatric patients, using a nuclei-isolation protocol optimized for frozen and archived surgical specimens. Relevant to the somatic-mosaic subtype, where resected epileptogenic tissue is the only accessible material.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[4],"sample_count":4,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42168328"],"publication_contexts":[{"context_id":"disorder:SLC35A2-CDG","publication":"PMID:42168328"}],"publication":"PMID:42168328","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42168328","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Found by GEO DataSets search and verified against NCBI E-utilities on 2026-08-20; title, sample count, and organism are GEO's own values. The GEO record lists no linked PMID, so the publication was matched by exact title agreement with PMID:42168328 rather than taken from the record."],"contexts":[{"id":"disorder:SLC35A2-CDG","name":"SLC35A2-congenital disorder of glycosylation","kind":"Disorder","source_path":"kb/disorders/SLC35A2-CDG.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/SLC35A2-CDG.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/SLC35A2-congenital_disorder_of_glycosylation.html#dataset-geo-gse318030"}],"context_names":["SLC35A2-congenital disorder of glycosylation"],"disease_names":["SLC35A2-congenital disorder of glycosylation"],"disease_name":"SLC35A2-congenital disorder of glycosylation","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/SLC35A2-CDG.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/SLC35A2-CDG.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/SLC35A2-congenital_disorder_of_glycosylation.html#dataset-geo-gse318030"]},{"id":"dataset:geo:gse318067","accession":"geo:GSE318067","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE318067","title":"Analysis of peripheral blood transcript and protein expression across adult systemic lupus erythematosus (SLE) and adult dermatomyositis (DM) patients, each compared to respective healthy matched control subjects.","alternate_titles":[],"description":"The study interrogates SLE and DM gene expression measurements across three platforms: Affymetrix transcriptomics, SomaLogic proteomics, and Rules Based Medicine (RBM) proteomics. Patients are matched 1:1 with healthy donor subjects by age, ethnicity, and sex. DM patients are matched 1:3 with SLE patients by the same criteria. All patients have been treated for at least one year, and represent patients receiving standard treatment care for the respective diseases. The data posted contain SLE patients in support of the paper Distinct Interferon and Intracellular Signaling Signatures in Systemic Lupus Erythematosus and Dermatomyositis by Integrative Transcriptomic and Proteomic Analysis.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[82],"sample_count":82,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41870980"],"publication_contexts":[{"context_id":"disorder:Dermatomyositis","publication":"PMID:41870980"}],"publication":"PMID:41870980","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41870980","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Dermatomyositis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Dermatomyositis","name":"Dermatomyositis","kind":"Disorder","source_path":"kb/disorders/Dermatomyositis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dermatomyositis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Dermatomyositis.html#dataset-geo-gse318067"}],"context_names":["Dermatomyositis"],"disease_names":["Dermatomyositis"],"disease_name":"Dermatomyositis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Dermatomyositis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dermatomyositis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Dermatomyositis.html#dataset-geo-gse318067"]},{"id":"dataset:geo:gse318177","accession":"geo:GSE318177","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE318177","title":"DNA methylation in episodic migraine and medication overuse headache.","alternate_titles":[],"description":"These data were generated within the Epimode project - a pilot, longitudinal, prospective, observational study designed to investigate DNA methylation in headache disorders. 20 episodic migraineurs (EM), 25 medication overuse headache patients (MOH) and 13 healthy controls (HC) were enrolled in the study. EM and HC samples were collected at baseline (T0) and ath the follow-up visit 6 months later (T1). MOH samples were collected at baseline (T0), at treatment time point (T1) and at the follow-up visits after 2 (T2) and 6 (T3) months from the therapeutic intervention.","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[142],"sample_count":142,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41721229"],"publication_contexts":[{"context_id":"disorder:Migraine","publication":"PMID:41721229"}],"publication":"PMID:41721229","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41721229","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Migraine (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Migraine","name":"Migraine","kind":"Disorder","source_path":"kb/disorders/Migraine.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Migraine.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Migraine.html#dataset-geo-gse318177"}],"context_names":["Migraine"],"disease_names":["Migraine"],"disease_name":"Migraine","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Migraine.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Migraine.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Migraine.html#dataset-geo-gse318177"]},{"id":"dataset:geo:gse318183","accession":"geo:GSE318183","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE318183","title":"Small RNA Sequencing of Exosomal MicroRNAs in Sera from Patients with Echinococcus granulosus Infection","alternate_titles":[],"description":"This project aimed to explore the potential roles of exosomal microRNAs (miRNAs) in cystic echinococcosis by extracting and analyzing exosomes and their cargo miRNAs from the sera of patients with Echinococcus granulosus infection. First, serum exosomes were isolated and purified via size-exclusion chromatography with strict quality control, followed by morphological identification of exosomes using negative-staining transmission electron microscopy. Subsequently, exosomal RNA was extracted, and small RNA libraries were constructed with the Illumina TruSeq Small RNA Kit for single-end 50 bp sequencing on the Illumina Hiseq 2000/2500 platform.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[8],"sample_count":8,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Cystic echinococcosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Cystic_Echinococcosis","name":"Cystic echinococcosis","kind":"Disorder","source_path":"kb/disorders/Cystic_Echinococcosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cystic_Echinococcosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cystic_echinococcosis.html#dataset-geo-gse318183"}],"context_names":["Cystic echinococcosis"],"disease_names":["Cystic echinococcosis"],"disease_name":"Cystic echinococcosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cystic_Echinococcosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cystic_Echinococcosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cystic_echinococcosis.html#dataset-geo-gse318183"]},{"id":"dataset:geo:gse318551","accession":"geo:GSE318551","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE318551","title":"TRalpha Deficiency Drives Sarcopenia by Disrupting Perimitochondrial Targeting of Pink1 mRNA and Mitophagy","alternate_titles":[],"description":"Spatial transcriptomics linking thyroid hormone receptor alpha deficiency to sarcopenia through PINK1-dependent mitophagy, bearing directly on the defective-mitophagy component of pathophysiology#Mitochondrial Dysfunction and Oxidative Stress.","alternate_descriptions":[],"data_types":["SPATIAL_TRANSCRIPTOMICS"],"data_type_labels":["Spatially resolved transcriptomics"],"data_type_label":"Spatially resolved transcriptomics","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Mouse data, no linked publication in the GEO record. Selected by manual relevance triage and accession-verified. No evidence block, as above."],"contexts":[{"id":"disorder:Sarcopenia","name":"Sarcopenia","kind":"Disorder","source_path":"kb/disorders/Sarcopenia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sarcopenia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Sarcopenia.html#dataset-geo-gse318551"}],"context_names":["Sarcopenia"],"disease_names":["Sarcopenia"],"disease_name":"Sarcopenia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Sarcopenia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sarcopenia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Sarcopenia.html#dataset-geo-gse318551"]},{"id":"dataset:geo:gse318601","accession":"geo:GSE318601","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE318601","title":"Early differential impact of MeCP2 mutations on functional networks in Rett syndrome patient-derived human cortical organoids [RNA-Seq]","alternate_titles":[],"description":"Human cerebral organoids derived from induced pluripotent stem cells can recapture early developmental processes and reveal changes involving neurodevelopmental disorders. Mutations in the X-linked methyl-CpG binding protein 2 (MECP2) gene are associated with Rett syndrome, and disease severity varies depending on the location and type of mutation. Here, we focused on neuronal activity in Rett syndrome patient-derived organoids, analyzing two types of MECP2 mutations—a missense mutation (R306C) and a truncating mutation (V247X)—using calcium imaging with three-photon microscopy.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[8],"sample_count":8,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41980938"],"publication_contexts":[{"context_id":"disorder:Rett_Syndrome","publication":"PMID:41980938"}],"publication":"PMID:41980938","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41980938","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Rett Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Rett_Syndrome","name":"Rett Syndrome","kind":"Disorder","source_path":"kb/disorders/Rett_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rett_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Rett_Syndrome.html#dataset-geo-gse318601"}],"context_names":["Rett Syndrome"],"disease_names":["Rett Syndrome"],"disease_name":"Rett Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Rett_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rett_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Rett_Syndrome.html#dataset-geo-gse318601"]},{"id":"dataset:geo:gse318816","accession":"geo:GSE318816","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE318816","title":"Blood-based Molecular Endotyping of Fibrotic Hypersensitivity Pneumonitis Identifies Two Immune Subtypes with Divergent Clinical Outcomes","alternate_titles":[],"description":"Fibrotic hypersensitivity pneumonitis (fHP) is an antigen driven deadly interstitial lung disease with limited treatment options. Using multiple analysis algorithms, we identified two molecular endotypes with divergent immune signatures in transcriptome of whole blood from a fHP cohort and validated in transcriptomes from whole blood, peripheral blood mononuclear cells, bronchoalveolar lavage, surgical lung biopsy tissue, and in the proteome from blood plasma.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[126],"sample_count":126,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Hypersensitivity pneumonitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Hypersensitivity_Pneumonitis","name":"Hypersensitivity pneumonitis","kind":"Disorder","source_path":"kb/disorders/Hypersensitivity_Pneumonitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hypersensitivity_Pneumonitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hypersensitivity_pneumonitis.html#dataset-geo-gse318816"}],"context_names":["Hypersensitivity pneumonitis"],"disease_names":["Hypersensitivity pneumonitis"],"disease_name":"Hypersensitivity pneumonitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hypersensitivity_Pneumonitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hypersensitivity_Pneumonitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hypersensitivity_pneumonitis.html#dataset-geo-gse318816"]},{"id":"dataset:geo:gse318927","accession":"geo:GSE318927","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE318927","title":"Macrophages in Neurofibroma Malignant Progression","alternate_titles":[],"description":"Neurofibromatosis type 1 (NF1) is characterized by the development of benign nerve sheath tumors named plexiform neurofibromas (PNFs). In 10–15% of patients, these tumors undergo malignant transformation into aggressive malignant peripheral nerve sheath tumors (MPNSTs), which are associated with poor prognosis and limited treatment options. The cellular and molecular mechanisms driving this malignant progression remain poorly understood, hindering the development of effective therapies. To address this gap, we performed comprehensive single cell RNA sequencing on 9 PNF and 5 MPNST clinical samples.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[14],"sample_count":14,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41930352"],"publication_contexts":[{"context_id":"disorder:Neurofibroma","publication":"PMID:41930352"}],"publication":"PMID:41930352","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41930352","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Neurofibroma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Neurofibroma","name":"Neurofibroma","kind":"Disorder","source_path":"kb/disorders/Neurofibroma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Neurofibroma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Neurofibroma.html#dataset-geo-gse318927"}],"context_names":["Neurofibroma"],"disease_names":["Neurofibroma"],"disease_name":"Neurofibroma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Neurofibroma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Neurofibroma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Neurofibroma.html#dataset-geo-gse318927"]},{"id":"dataset:geo:gse319077","accession":"geo:GSE319077","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE319077","title":"Excitatory cortical neurons from CDKL5 deficiency disorder patient-derived organoids show early hyperexcitability not identified in neurogenin2 induced neurons [RNA-Seq]","alternate_titles":[],"description":"RNA sequencing of patient/isogenic neuronal cultures from the cortical organoid differentiation study. The paper also compares NGN2 induction; the organoid cultures were dissociated for functional assays. Early cortical-network hyperexcitability differs from the negative NGN2 result, and RNA-seq findings must not be conflated with electrophysiological measurements. HS3ST1 RNA-seq reduction was not statistically significant by follow-up qPCR.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[18],"sample_count":18,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:11411","label":"CDKL5","display_label":"CDKL5","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/11411"}],"genes":["CDKL5"],"platforms":[],"platform":null,"publications":["PMID:40930428"],"publication_contexts":[{"context_id":"disorder:CDKL5_Deficiency_Disorder","publication":"PMID:40930428"}],"publication":"PMID:40930428","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40930428","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Accession, title, organism and sample count verified against the fetched GEO record on 2026-10-01. Interpret expression changes with the study design and model limitations described here."],"contexts":[{"id":"disorder:CDKL5_Deficiency_Disorder","name":"CDKL5 Deficiency Disorder","kind":"Disorder","source_path":"kb/disorders/CDKL5_Deficiency_Disorder.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/CDKL5_Deficiency_Disorder.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/CDKL5_Deficiency_Disorder.html#dataset-geo-gse319077"}],"context_names":["CDKL5 Deficiency Disorder"],"disease_names":["CDKL5 Deficiency Disorder"],"disease_name":"CDKL5 Deficiency Disorder","same_context_model_ids":["model:kb/disorders/CDKL5_Deficiency_Disorder.yaml:CLIP170-Dynactin and Cargo Transport Assays","model:kb/disorders/CDKL5_Deficiency_Disorder.yaml:Isogenic R59Ter Neuronal Phosphoproteomics","model:kb/disorders/CDKL5_Deficiency_Disorder.yaml:MAP1S Microtubule Dynamics and Rescue Assays","model:kb/disorders/CDKL5_Deficiency_Disorder.yaml:NGN2-Induced Patient Neurons","model:kb/disorders/CDKL5_Deficiency_Disorder.yaml:Patient-Derived Cortical Organoid Neurons","model:kb/disorders/CDKL5_Deficiency_Disorder.yaml:Postsynaptic Condensate Reconstitution","model:kb/disorders/CDKL5_Deficiency_Disorder.yaml:R550Ter Patient iPSC Base-Editing Rescue"],"candidate_model_ids":["model:kb/disorders/CDKL5_Deficiency_Disorder.yaml:NGN2-Induced Patient Neurons","model:kb/disorders/CDKL5_Deficiency_Disorder.yaml:Patient-Derived Cortical Organoid Neurons"],"association_basis":"Same publication as a NAM (candidate)","nam_disease_context":"Same publication as a NAM (candidate)","source_paths":["kb/disorders/CDKL5_Deficiency_Disorder.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/CDKL5_Deficiency_Disorder.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/CDKL5_Deficiency_Disorder.html#dataset-geo-gse319077"]},{"id":"dataset:geo:gse319080","accession":"geo:GSE319080","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE319080","title":"Excitatory cortical neurons from CDKL5 deficiency disorder patient-derived organoids show early hyperexcitability not identified in neurogenin2 induced neurons [Ampliseq]","alternate_titles":[],"description":"CDKL5 deficiency disorder (CDD) is a rare developmental and epileptic encephalopathy resulting from variants in cyclin-dependent kinase-like 5 (CDKL5) that lead to impaired kinase activity or loss of function. CDD is one of the most common genetic etiologies identified in epilepsy cohorts. To study how CDKL5 variants impact human neuronal activity, gene expression and morphology, CDD patient-derived induced pluripotent stem cells and their isogenic controls were differentiated into excitatory neurons using either an NGN2 induction protocol or a guided cortical organoid differentiation.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40930428"],"publication_contexts":[{"context_id":"disorder:Genetic_Developmental_and_Epileptic_Encephalopathy","publication":"PMID:40930428"}],"publication":"PMID:40930428","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40930428","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Genetic Developmental and Epileptic Encephalopathy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Genetic_Developmental_and_Epileptic_Encephalopathy","name":"Genetic Developmental and Epileptic Encephalopathy","kind":"Disorder","source_path":"kb/disorders/Genetic_Developmental_and_Epileptic_Encephalopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Genetic_Developmental_and_Epileptic_Encephalopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Genetic_Developmental_and_Epileptic_Encephalopathy.html#dataset-geo-gse319080"}],"context_names":["Genetic Developmental and Epileptic Encephalopathy"],"disease_names":["Genetic Developmental and Epileptic Encephalopathy"],"disease_name":"Genetic Developmental and Epileptic Encephalopathy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Genetic_Developmental_and_Epileptic_Encephalopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Genetic_Developmental_and_Epileptic_Encephalopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Genetic_Developmental_and_Epileptic_Encephalopathy.html#dataset-geo-gse319080"]},{"id":"dataset:geo:gse319253","accession":"geo:GSE319253","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE319253","title":"Eicosapentaenoic Acid Reprograms Cerebrovascular Metabolism and Impairs Repair after Brain Injury, with Relevance to Chronic Traumatic Encephalopathy [human_brain_OnurE_RNA-seq]","alternate_titles":[],"description":"Repetitive mild traumatic brain injury (rmTBI) precedes chronic traumatic encephalopathy (CTE) and involves neurovascular dysfunction. Omega-3 polyunsaturated fatty acids (PUFA) are promoted as neuroprotective, but long-term effects after brain injury remain uncertain. We uncover a metabolic vulnerability associated with cerebral accumulation of eicosapentaenoic acid (EPA), a major PUFA derived from fish oil. In a fish oil diet model, EPA accumulates at baseline yet is selectively depleted after rmTBI, consistent with mobilization during injury-associated metabolic remodeling. This pattern coincides with matrix remodeling, endothelial degeneration, and impaired neurovascular function.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[24],"sample_count":24,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Chronic Traumatic Encephalopathy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Chronic_Traumatic_Encephalopathy","name":"Chronic Traumatic Encephalopathy","kind":"Disorder","source_path":"kb/disorders/Chronic_Traumatic_Encephalopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Traumatic_Encephalopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chronic_Traumatic_Encephalopathy.html#dataset-geo-gse319253"}],"context_names":["Chronic Traumatic Encephalopathy"],"disease_names":["Chronic Traumatic Encephalopathy"],"disease_name":"Chronic Traumatic Encephalopathy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chronic_Traumatic_Encephalopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Traumatic_Encephalopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chronic_Traumatic_Encephalopathy.html#dataset-geo-gse319253"]},{"id":"dataset:geo:gse319516","accession":"geo:GSE319516","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE319516","title":"Obesity-associated meta-inflammation alters influenza A antiviral responses in Göttingen minipigs","alternate_titles":[],"description":"Obesity is a well-recognized risk factor for increased severity following influenza A virus (IAV) infection, likely by promoting meta-inflammation and immune dysregulation, but its effects on antiviral and inflammatory responses remain poorly understood. Using a Göttingen minipig model of diet-induced obesity, we compared antiviral and inflammatory responses before and after IAV infection. Respiratory tract transcriptomics and histopathology revealed no clear obesity-associated immune or inflammatory changes in uninfected minipigs. In contrast, obese pigs showed reduced viral clearance in nasal mucosal tissue accompanied by altered antiviral gene expression pattern four days post infection.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9823","label":"Sus scrofa","display_label":"pig","url":"http://purl.obolibrary.org/obo/NCBITaxon_9823"}],"organism_labels":["Sus scrofa"],"organism_label":"Sus scrofa","sample_types":[],"sample_type_labels":[],"sample_counts":[25],"sample_count":25,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Influenza (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Influenza","name":"Influenza","kind":"Disorder","source_path":"kb/disorders/Influenza.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Influenza.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Influenza.html#dataset-geo-gse319516"}],"context_names":["Influenza"],"disease_names":["Influenza"],"disease_name":"Influenza","same_context_model_ids":["model:kb/disorders/Influenza.yaml:Immune-competent microvascularized lung-on-a-chip (IC-LOC) severe H1N1 model"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Influenza.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Influenza.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Influenza.html#dataset-geo-gse319516"]},{"id":"dataset:geo:gse319770","accession":"geo:GSE319770","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE319770","title":"Integrative Molecular Analyses of Inflammatory and Autoimmune Signals in Cardiac Sarcoidosis [snRNA-Seq]","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[41],"sample_count":41,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42206386"],"publication_contexts":[{"context_id":"disorder:Cardiac_Sarcoidosis","publication":"PMID:42206386"}],"publication":"PMID:42206386","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42206386","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Cardiac_Sarcoidosis (scripts/discover_datasets.py) and verified with just verify-datasets. Cardiac sarcoidosis is named in the GEO series title. Companion Xenium series of the same study is geo:GSE319771."],"contexts":[{"id":"disorder:Cardiac_Sarcoidosis","name":"Cardiac Sarcoidosis","kind":"Disorder","source_path":"kb/disorders/Cardiac_Sarcoidosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cardiac_Sarcoidosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cardiac_Sarcoidosis.html#dataset-geo-gse319770"}],"context_names":["Cardiac Sarcoidosis"],"disease_names":["Cardiac Sarcoidosis"],"disease_name":"Cardiac Sarcoidosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cardiac_Sarcoidosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cardiac_Sarcoidosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cardiac_Sarcoidosis.html#dataset-geo-gse319770"]},{"id":"dataset:geo:gse319771","accession":"geo:GSE319771","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE319771","title":"Integrative Molecular Analyses of Inflammatory and Autoimmune Signals in Cardiac Sarcoidosis [Xenium]","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[18],"sample_count":18,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42206386"],"publication_contexts":[{"context_id":"disorder:Cardiac_Sarcoidosis","publication":"PMID:42206386"}],"publication":"PMID:42206386","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42206386","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Cardiac_Sarcoidosis (scripts/discover_datasets.py) and verified with just verify-datasets. Cardiac sarcoidosis is named in the GEO series title. Companion snRNA-seq series of the same study is geo:GSE319770. GEO's own platform typing for this Xenium in-situ series is recorded as MICROARRAY by the discovery index."],"contexts":[{"id":"disorder:Cardiac_Sarcoidosis","name":"Cardiac Sarcoidosis","kind":"Disorder","source_path":"kb/disorders/Cardiac_Sarcoidosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cardiac_Sarcoidosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cardiac_Sarcoidosis.html#dataset-geo-gse319771"}],"context_names":["Cardiac Sarcoidosis"],"disease_names":["Cardiac Sarcoidosis"],"disease_name":"Cardiac Sarcoidosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cardiac_Sarcoidosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cardiac_Sarcoidosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cardiac_Sarcoidosis.html#dataset-geo-gse319771"]},{"id":"dataset:geo:gse319777","accession":"geo:GSE319777","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE319777","title":"Therapeutic TG2 Inhibition Reverses Systemic Multiomic Dysregulation in Celiac Disease","alternate_titles":[],"description":"Background and Aims: Celiac disease (CeD) is an autoimmune disease triggered by dietary gluten in genetically predisposed individuals. Deamidation of gluten peptides by the CeD autoantigen and enzyme transglutaminase 2 (TG2) is central to the pathogenesis of CeD. Inhibition of TG2 with the specific inhibitor ZED1227 effectively prevents gluten-induced histological damage in CeD patients. Here we aimed to explore the blood DNA methylomic changes in ZED1227-treated CeD patients undergoing a gluten challenge. Results: Drug treatment revealed consistent patterns suggesting normalization of the DNA methylome indicating that ZED1227 attenuated the systemic responses to gluten challenge.","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[72],"sample_count":72,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42032651"],"publication_contexts":[{"context_id":"disorder:Celiac_Disease","publication":"PMID:42032651"}],"publication":"PMID:42032651","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42032651","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Celiac Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Celiac_Disease","name":"Celiac Disease","kind":"Disorder","source_path":"kb/disorders/Celiac_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Celiac_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Celiac_Disease.html#dataset-geo-gse319777"}],"context_names":["Celiac Disease"],"disease_names":["Celiac Disease"],"disease_name":"Celiac Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Celiac_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Celiac_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Celiac_Disease.html#dataset-geo-gse319777"]},{"id":"dataset:geo:gse319802","accession":"geo:GSE319802","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE319802","title":"Blood-brain barrier disruption in sports-related traumatic encephalopathy syndrome","alternate_titles":[],"description":"Cerebrovascular disruption has been implicated in the pathophysiology of head trauma and chronic traumatic encephalopathy (CTE). However, the long-term consequences of repetitive head trauma on blood–brain barrier (BBB) integrity and its link to cognitive function remains unknown. Here, using dynamic contrast enhanced MRI (DCE-MRI), we show that BBB disruption can be detected years after combat and collision sports athletes (n = 47) have retired from their respective sports. A subgroup of individuals (n = 17) with extensive BBB disruption displayed worse cognitive decline compared to those with less extensive disruption.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[65],"sample_count":65,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Chronic Traumatic Encephalopathy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Chronic_Traumatic_Encephalopathy","name":"Chronic Traumatic Encephalopathy","kind":"Disorder","source_path":"kb/disorders/Chronic_Traumatic_Encephalopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Traumatic_Encephalopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chronic_Traumatic_Encephalopathy.html#dataset-geo-gse319802"}],"context_names":["Chronic Traumatic Encephalopathy"],"disease_names":["Chronic Traumatic Encephalopathy"],"disease_name":"Chronic Traumatic Encephalopathy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chronic_Traumatic_Encephalopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Traumatic_Encephalopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chronic_Traumatic_Encephalopathy.html#dataset-geo-gse319802"]},{"id":"dataset:geo:gse320199","accession":"geo:GSE320199","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE320199","title":"Transcriptomic analyses of mortality in HIV-associated Pneumocystis pneumonia","alternate_titles":[],"description":"Pneumocystis jirovecii pneumonia (PCP) remains a leading cause of respiratory failure and mortality in individuals with advanced HIV. While severe disease is classically attributed to hyperinflammation, the specific biological determinants driving fatal outcomes in patients remain poorly understood. To address this, we employed an integrated systems biology approach, performing transcriptomics, proteomics, and metabolomics on bronchoalveolar lavage fluid from a prospective cohort of 42 patients with HIV-associated PCP. We demonstrate that mortality is not primarily driven by uncontrolled fungal burden or isolated hyperinflammation, but by profound immunometabolic failure.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[24],"sample_count":24,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Pneumocystis Pneumonia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Pneumocystis_Pneumonia","name":"Pneumocystis Pneumonia","kind":"Disorder","source_path":"kb/disorders/Pneumocystis_Pneumonia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pneumocystis_Pneumonia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pneumocystis_Pneumonia.html#dataset-geo-gse320199"}],"context_names":["Pneumocystis Pneumonia"],"disease_names":["Pneumocystis Pneumonia"],"disease_name":"Pneumocystis Pneumonia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Pneumocystis_Pneumonia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pneumocystis_Pneumonia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Pneumocystis_Pneumonia.html#dataset-geo-gse320199"]},{"id":"dataset:geo:gse320212","accession":"geo:GSE320212","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE320212","title":"Identifying Senescence and Immune Biomarkers Predictive of Benefit to Combined CDK4/6 and PD-1 Blockade in Dedifferentiated Liposarcoma: Single-Cell RNA-seq of Serial Tumor Biopsies","alternate_titles":[],"description":"This dataset comes from an exploratory correlatives sub-study embedded within NCT04438824, a single-arm, open-label phase II trial evaluating the combination of the CDK4/6 inhibitor palbociclib and the PD-1 inhibitor INCMGA00012 in patients with advanced well-differentiated or dedifferentiated liposarcoma. The dbGaP submission is limited to the first 12 patients enrolled on the trial, for whom protocol-mandated tumor biopsies were collected for single-cell RNA sequencing. Single-cell RNASeq was performed to characterize cellular composition and transcriptional states within the tumor microenvironment in this pilot cohort.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[23],"sample_count":23,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41325133"],"publication_contexts":[{"context_id":"disorder:Liposarcoma","publication":"PMID:41325133"}],"publication":"PMID:41325133","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41325133","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Liposarcoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Liposarcoma","name":"Liposarcoma","kind":"Disorder","source_path":"kb/disorders/Liposarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Liposarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Liposarcoma.html#dataset-geo-gse320212"}],"context_names":["Liposarcoma"],"disease_names":["Liposarcoma"],"disease_name":"Liposarcoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Liposarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Liposarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Liposarcoma.html#dataset-geo-gse320212"]},{"id":"dataset:geo:gse320504","accession":"geo:GSE320504","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE320504","title":"Convergent Transcriptomic Signatures in Blood Link Lumbar Disc Herniation and Cervical Artery Dissection in Young Adults","alternate_titles":[],"description":"Recurrent lumbar disc herniation (rLDH) and cervical artery dissection (CeAD) are significant neurological manifestations of undifferentiated connective tissue dysplasia (UCTD) in young adults. Molecular and histopathological evidence points to impaired cellular differentiation and aberrant extracellular matrix organization in these patients. Nevertheless, the pathogenic mechanisms of UCTD and the basis for its clinical heterogeneity remain largely unknown. Here, we conducted the first comparative transcriptome-wide analysis of peripheral blood mRNA in two UCTD cohorts—19 patients with CeAD and 12 with rLDH—alongside 18 healthy volunteers.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[49],"sample_count":49,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Cervical Artery Dissection (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Cervical_Artery_Dissection","name":"Cervical Artery Dissection","kind":"Disorder","source_path":"kb/disorders/Cervical_Artery_Dissection.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cervical_Artery_Dissection.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cervical_Artery_Dissection.html#dataset-geo-gse320504"}],"context_names":["Cervical Artery Dissection"],"disease_names":["Cervical Artery Dissection"],"disease_name":"Cervical Artery Dissection","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cervical_Artery_Dissection.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cervical_Artery_Dissection.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cervical_Artery_Dissection.html#dataset-geo-gse320504"]},{"id":"dataset:geo:gse322527","accession":"geo:GSE322527","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE322527","title":"Single-cell transcriptomes and T cell receptor sequences of CD4 or CD8 single positive T lymphocytes from peripheral blood or urine of lupus nephritis patients at flare.","alternate_titles":[],"description":"Proliferative lupus nephritis (LN) is triggered by deposition of autoantibodies in glomeruli and paralleled by a T cell-rich kidney infiltrate. Although these T cells have been attributed with propagation of tissue injury, it is unclear how they are activated and whether T cell autoreactivity drives the local inflammation. Kidney-infiltrating T cells are also observed in urine, where they have high resemblance with interstitial T cells. Therefore, urinary T cells are a proxy to investigate tissue pathogenesis. Here, we analyzed urinary T cells to elucidate if a kidney-specific T cell autoimmune reaction contributes to tubulointerstitial inflammation in LN.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[26],"sample_count":26,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Lupus Nephritis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Lupus_Nephritis","name":"Lupus Nephritis","kind":"Disorder","source_path":"kb/disorders/Lupus_Nephritis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Lupus_Nephritis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Lupus_Nephritis.html#dataset-geo-gse322527"}],"context_names":["Lupus Nephritis"],"disease_names":["Lupus Nephritis"],"disease_name":"Lupus Nephritis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Lupus_Nephritis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Lupus_Nephritis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Lupus_Nephritis.html#dataset-geo-gse322527"]},{"id":"dataset:geo:gse322635","accession":"geo:GSE322635","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE322635","title":"Humanin and MOTS-c Attenuate Atrial Fibrillation by Suppressing Fibrosis and Mitochondrial Dysfunction in murine models","alternate_titles":[],"description":"BACKGROUND: Atrial fibrillation (AF) is the most common clinical arrhythmia associated with mitochondrial dysfunction, oxidative stress, and atrial fibrosis. Mitochondrial-derived peptides (MDPs) including humanin (HN) and MOTS-c, demonstrated potent cytoprotective effects, but their role in AF remains elusive. METHODS: Public GEO database, immunohistochemistry and immunofluorescence were applied to determine their expressions in atrial tissues. Plasma peptide levels were measured in a clinical cohort.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10116","label":"Rattus norvegicus","display_label":"rat","url":"http://purl.obolibrary.org/obo/NCBITaxon_10116"}],"organism_labels":["Rattus norvegicus"],"organism_label":"Rattus norvegicus","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42193373"],"publication_contexts":[{"context_id":"disorder:Atrial_Fibrillation","publication":"PMID:42193373"}],"publication":"PMID:42193373","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42193373","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Atrial Fibrillation (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Atrial_Fibrillation","name":"Atrial Fibrillation","kind":"Disorder","source_path":"kb/disorders/Atrial_Fibrillation.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Atrial_Fibrillation.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Atrial_Fibrillation.html#dataset-geo-gse322635"}],"context_names":["Atrial Fibrillation"],"disease_names":["Atrial Fibrillation"],"disease_name":"Atrial Fibrillation","same_context_model_ids":["model:kb/disorders/Atrial_Fibrillation.yaml:Palmitate-treated human iPSC-derived atrial cardiomyocytes"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Atrial_Fibrillation.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Atrial_Fibrillation.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Atrial_Fibrillation.html#dataset-geo-gse322635"]},{"id":"dataset:geo:gse324111","accession":"geo:GSE324111","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE324111","title":"Vascular endothelial growth factor receptors 1 and 3 mediate placental trophoblast leptin production in preeclampsia, inducing vascular dysfunction","alternate_titles":[],"description":"Heightened soluble FMS-like tyrosine kinase-1 (sFlt-1) level is a hallmark of preeclampsia patients and induces a state of angiogenic imbalance by sequestering free vascular endothelial growth factor (VEGF) and placental growth factor (PlGF). The receptors for VEGF and PlGF, membrane-bound VEGFR, are expressed in placental trophoblast cells, but their functions in this cell type are largely unknown. Placenta production of leptin significantly increases in preeclampsia, and we recently showed leptin induces placental and vascular endothelial dysfunction in pregnancy. We hypothesized that inappropriately high sFlt-1 in preeclampsia leads to an increase in trophoblast leptin production.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42422950"],"publication_contexts":[{"context_id":"disorder:Preeclampsia","publication":"PMID:42422950"}],"publication":"PMID:42422950","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42422950","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Preeclampsia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Preeclampsia","name":"Preeclampsia","kind":"Disorder","source_path":"kb/disorders/Preeclampsia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Preeclampsia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Preeclampsia.html#dataset-geo-gse324111"}],"context_names":["Preeclampsia"],"disease_names":["Preeclampsia"],"disease_name":"Preeclampsia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Preeclampsia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Preeclampsia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Preeclampsia.html#dataset-geo-gse324111"]},{"id":"dataset:geo:gse324136","accession":"geo:GSE324136","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE324136","title":"Integrative multi-omic analyses identify major axes of heterogeneity in chronic obstructive pulmonary disease and uncover their molecular contributors - ECLIPSE replication cohort","alternate_titles":[],"description":"Chronic Obstructive Pulmonary Disease (COPD) is a complex, heterogeneous disease. Traditional subtyping methods generally focus on either the clinical manifestations or the molecular endotypes of the disease, leading to classifications that only partially reflect disease heterogeneity. Here, we introduce a variational autoencoder-based subtyping pipeline that jointly embeds clinical and gene expression data into a single subject-level representation. We evaluate the framework in the COPDGene study, a large study of current and former smoking individuals with and without COPD.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[628],"sample_count":628,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Chronic Obstructive Pulmonary Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Chronic_Obstructive_Pulmonary_Disease","name":"Chronic_Obstructive_Pulmonary_Disease","kind":"Disorder","source_path":"kb/disorders/Chronic_Obstructive_Pulmonary_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Obstructive_Pulmonary_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chronic_Obstructive_Pulmonary_Disease.html#dataset-geo-gse324136"}],"context_names":["Chronic_Obstructive_Pulmonary_Disease"],"disease_names":["Chronic_Obstructive_Pulmonary_Disease"],"disease_name":"Chronic_Obstructive_Pulmonary_Disease","same_context_model_ids":["model:kb/disorders/Chronic_Obstructive_Pulmonary_Disease.yaml:Open-top vascularized alveolus-on-chip whole cigarette smoke model","model:kb/disorders/Chronic_Obstructive_Pulmonary_Disease.yaml:Patient-derived epithelial-endothelial COPD airway-on-a-chip"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Chronic_Obstructive_Pulmonary_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Obstructive_Pulmonary_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chronic_Obstructive_Pulmonary_Disease.html#dataset-geo-gse324136"]},{"id":"dataset:geo:gse324217","accession":"geo:GSE324217","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE324217","title":"A dual role for PGLYRP1 in host defense and immune regulation during B. pertussis infection","alternate_titles":[],"description":"Bordetella pertussis, the etiologic agent of whooping cough, remains a serious public health concern despite widespread vaccination. Improved therapeutics and vaccines are urgently needed to treat and prevent pertussis disease. Host recognition of bacterial peptidoglycan (PGN), including B. pertussis extracellular PGN fragment tracheal cytotoxin (TCT), shapes the immune response to infection. Peptidoglycan recognition proteins (PGLYRPs) are a conserved family of innate immune molecules which bind bacterial PGN. While they function as immune signaling receptors in arthropods, PGLYRPs in mammals have thus far been primarily recognized for their bactericidal activity.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41040336"],"publication_contexts":[{"context_id":"disorder:Pertussis","publication":"PMID:41040336"}],"publication":"PMID:41040336","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41040336","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Pertussis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Pertussis","name":"Pertussis","kind":"Disorder","source_path":"kb/disorders/Pertussis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pertussis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pertussis.html#dataset-geo-gse324217"}],"context_names":["Pertussis"],"disease_names":["Pertussis"],"disease_name":"Pertussis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Pertussis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pertussis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Pertussis.html#dataset-geo-gse324217"]},{"id":"dataset:geo:gse324301","accession":"geo:GSE324301","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE324301","title":"Mitochondrial DNA heteroplasmy drives cortical neuronal disturbances in human organoids harbouring the common m.3243A>G mutation","alternate_titles":[],"description":"Single-cell RNA-seq of human iPSC-derived cerebral organoid slices carrying m.3243A>G at varying heteroplasmy, generated as a cortical model because no animal carries the mutation. Reports heteroplasmy-dependent transcriptional shifts and preferential impairment of deep-layer neurons with axonal degeneration and apoptosis, compared against MELAS brain autopsy.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[7],"sample_count":7,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["The most direct public response to the human-model-mismatch gap recorded in this entry: a model with cortical architecture, which iPSC-derived neuron monocultures lack, validated against patient brain tissue. It still cannot produce a stroke-like episode - organoid slices have no vasculature and no seizure activity - so it addresses neuronal vulnerability rather than the episode itself. Deposited 2026 with no linked publication at the time of curation, so nothing here is attributed to a peer-reviewed report."],"contexts":[{"id":"disorder:MELAS_Syndrome","name":"MELAS Syndrome","kind":"Disorder","source_path":"kb/disorders/MELAS_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MELAS_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/MELAS_Syndrome.html#dataset-geo-gse324301"}],"context_names":["MELAS Syndrome"],"disease_names":["MELAS Syndrome"],"disease_name":"MELAS Syndrome","same_context_model_ids":["model:kb/disorders/MELAS_Syndrome.yaml:m.3243A>G patient iPSC-derived neurons"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/MELAS_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MELAS_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/MELAS_Syndrome.html#dataset-geo-gse324301"]},{"id":"dataset:geo:gse324689","accession":"geo:GSE324689","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE324689","title":"Post Kala Azar Dermal Leishmaniasis (PKDL) genome wide transcriptional profiling by bulk RNA-sequencing","alternate_titles":[],"description":"Post-kala-azar dermal leishmaniasis (PKDL), a dermal sequel of visceral leishmaniasis (VL), is considered an important reservoir that facilitates the transmission of VL. Although PKDL lesions demonstrate an overwhelming infiltration of CD8⁺ T cells, the molecular mechanisms regulating their recruitment to the skin remain poorly defined. To address this, bulk RNA sequencing was performed on dermal lesions from patients withPKDL and healthy controls to characterize the lesional chemokine and cytokine landscape associated with T-cell homing.Transcriptomic analysis revealed a significant upregulation of genes encoding T-cell chemoattractants, including CCL3, CCL4, CCL5, CCL17, CXCL9, and CXCL10,...","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[7],"sample_count":7,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42497210"],"publication_contexts":[{"context_id":"disorder:Leishmaniasis","publication":"PMID:42497210"}],"publication":"PMID:42497210","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42497210","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Leishmaniasis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Leishmaniasis","name":"Leishmaniasis","kind":"Disorder","source_path":"kb/disorders/Leishmaniasis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Leishmaniasis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Leishmaniasis.html#dataset-geo-gse324689"}],"context_names":["Leishmaniasis"],"disease_names":["Leishmaniasis"],"disease_name":"Leishmaniasis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Leishmaniasis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Leishmaniasis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Leishmaniasis.html#dataset-geo-gse324689"]},{"id":"dataset:geo:gse325064","accession":"geo:GSE325064","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE325064","title":"Distinct pathophysiological mechanisms of CEP152 variants in microcephaly and brain abnormalities","alternate_titles":[],"description":"Bulk RNA-sequencing of brains from Cep152 W105*/K897* and Q32P/Q32P patient-variant knock-in mice and matched controls, supporting analysis of variant-specific neuronal impairment.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[24],"sample_count":24,"conditions":["Cep152 W105*/K897* knock-in","Cep152 Q32P/Q32P knock-in","Wild-type controls"],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:29298","label":"CEP152","display_label":"CEP152","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/29298"}],"genes":["CEP152"],"platforms":[],"platform":null,"publications":["PMID:42086905"],"publication_contexts":[{"context_id":"disorder:Autosomal_Recessive_Primary_Microcephaly","publication":"PMID:42086905"}],"publication":"PMID:42086905","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42086905","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:42086905","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/42086905","reference_title":"Distinct pathophysiological mechanisms of CEP152 variants in microcephaly and brain abnormalities.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"both Cep152W105*/K897* and Cep152Q32P/Q32P knock-in mice displayed microcephaly","explanation":"The associated publication supports the patient-variant mouse dataset."}],"notes":[],"contexts":[{"id":"disorder:Autosomal_Recessive_Primary_Microcephaly","name":"Autosomal Recessive Primary Microcephaly","kind":"Disorder","source_path":"kb/disorders/Autosomal_Recessive_Primary_Microcephaly.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autosomal_Recessive_Primary_Microcephaly.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Recessive_Primary_Microcephaly.html#dataset-geo-gse325064"}],"context_names":["Autosomal Recessive Primary Microcephaly"],"disease_names":["Autosomal Recessive Primary Microcephaly"],"disease_name":"Autosomal Recessive Primary Microcephaly","same_context_model_ids":["model:kb/disorders/Autosomal_Recessive_Primary_Microcephaly.yaml:CDK5RAP2 patient-derived high-quantity brain organoids","model:kb/disorders/Autosomal_Recessive_Primary_Microcephaly.yaml:CETN3-knockout human cerebral organoids","model:kb/disorders/Autosomal_Recessive_Primary_Microcephaly.yaml:CIT kinase-dead and frameshift human forebrain organoids","model:kb/disorders/Autosomal_Recessive_Primary_Microcephaly.yaml:WDR62 patient-derived neural progenitor and cerebral organoid models"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Autosomal_Recessive_Primary_Microcephaly.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autosomal_Recessive_Primary_Microcephaly.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Recessive_Primary_Microcephaly.html#dataset-geo-gse325064"]},{"id":"dataset:geo:gse325168","accession":"geo:GSE325168","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE325168","title":"Base editing restores CDKL5 expression and rescues neuronal deficits in a patient-derived model of CDKL5 deficiency disorder","alternate_titles":[],"description":"RNA sequencing of female patient-derived R550Ter iPSC neurons, ABE-corrected derivatives and a wild-type-active-X comparator from the same donor. Six samples per condition provide an 18-sample comparison. Shared donor background reduces one source of confounding, but X-inactivation, clone selection and editing effects remain; the lines cannot be claimed to differ only at the CDKL5 nucleotide.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[18],"sample_count":18,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:11411","label":"CDKL5","display_label":"CDKL5","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/11411"}],"genes":["CDKL5"],"platforms":[],"platform":null,"publications":["PMID:41963441"],"publication_contexts":[{"context_id":"disorder:CDKL5_Deficiency_Disorder","publication":"PMID:41963441"}],"publication":"PMID:41963441","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41963441","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Accession, title, organism and sample count verified against the fetched GEO record on 2026-10-01. Interpret expression changes with the study design and model limitations described here."],"contexts":[{"id":"disorder:CDKL5_Deficiency_Disorder","name":"CDKL5 Deficiency Disorder","kind":"Disorder","source_path":"kb/disorders/CDKL5_Deficiency_Disorder.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/CDKL5_Deficiency_Disorder.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/CDKL5_Deficiency_Disorder.html#dataset-geo-gse325168"}],"context_names":["CDKL5 Deficiency Disorder"],"disease_names":["CDKL5 Deficiency Disorder"],"disease_name":"CDKL5 Deficiency Disorder","same_context_model_ids":["model:kb/disorders/CDKL5_Deficiency_Disorder.yaml:CLIP170-Dynactin and Cargo Transport Assays","model:kb/disorders/CDKL5_Deficiency_Disorder.yaml:Isogenic R59Ter Neuronal Phosphoproteomics","model:kb/disorders/CDKL5_Deficiency_Disorder.yaml:MAP1S Microtubule Dynamics and Rescue Assays","model:kb/disorders/CDKL5_Deficiency_Disorder.yaml:NGN2-Induced Patient Neurons","model:kb/disorders/CDKL5_Deficiency_Disorder.yaml:Patient-Derived Cortical Organoid Neurons","model:kb/disorders/CDKL5_Deficiency_Disorder.yaml:Postsynaptic Condensate Reconstitution","model:kb/disorders/CDKL5_Deficiency_Disorder.yaml:R550Ter Patient iPSC Base-Editing Rescue"],"candidate_model_ids":["model:kb/disorders/CDKL5_Deficiency_Disorder.yaml:R550Ter Patient iPSC Base-Editing Rescue"],"association_basis":"Same publication as a NAM (candidate)","nam_disease_context":"Same publication as a NAM (candidate)","source_paths":["kb/disorders/CDKL5_Deficiency_Disorder.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/CDKL5_Deficiency_Disorder.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/CDKL5_Deficiency_Disorder.html#dataset-geo-gse325168"]},{"id":"dataset:geo:gse3252","accession":"geo:GSE3252","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE3252","title":"Laminin-deficient muscular dystrophy, dy/dy diaphragm","alternate_titles":[],"description":"Microarray profiling of eight-week-old dy/dy mouse diaphragm. It samples respiratory muscle pathology in a model; prominent functional diaphragm failure is not established as the driver of human MDC1A respiratory decline, where intercostal and accessory weakness is important.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"house mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[8],"sample_count":8,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:6482","label":"LAMA2","display_label":"LAMA2","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/6482"}],"genes":["LAMA2"],"platforms":[],"platform":null,"publications":["PMID:16368874"],"publication_contexts":[{"context_id":"disorder:Congenital_Merosin-deficient_Muscular_Dystrophy_1A","publication":"PMID:16368874"}],"publication":"PMID:16368874","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/16368874","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["The dataset-discovery tool tagged this GENE_ONLY, meaning the match ran through the gene name rather than the disease name. Triaged manually and kept: the GEO title and summary both name laminin/merosin-deficient muscular dystrophy in the dy/dy mouse, so it is a true positive that the disease-name matcher missed because the record predates the LAMA2-CMD nomenclature."],"contexts":[{"id":"disorder:Congenital_Merosin-deficient_Muscular_Dystrophy_1A","name":"Congenital Merosin-deficient Muscular Dystrophy 1A","kind":"Disorder","source_path":"kb/disorders/Congenital_Merosin-deficient_Muscular_Dystrophy_1A.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Congenital_Merosin-deficient_Muscular_Dystrophy_1A.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Congenital_Merosin-deficient_Muscular_Dystrophy_1A.html#dataset-geo-gse3252"}],"context_names":["Congenital Merosin-deficient Muscular Dystrophy 1A"],"disease_names":["Congenital Merosin-deficient Muscular Dystrophy 1A"],"disease_name":"Congenital Merosin-deficient Muscular Dystrophy 1A","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Congenital_Merosin-deficient_Muscular_Dystrophy_1A.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Congenital_Merosin-deficient_Muscular_Dystrophy_1A.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Congenital_Merosin-deficient_Muscular_Dystrophy_1A.html#dataset-geo-gse3252"]},{"id":"dataset:geo:gse32563","accession":"geo:GSE32563","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE32563","title":"Differential Gene Expression in Angelman syndrome deletion vs. int dup(15) Human Lymphocytes","alternate_titles":[],"description":"Human peripheral-blood microarray dataset comparing Angelman deletion cases and reciprocal 15q duplication cases to identify shared and divergent transcriptional signatures.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":["Angelman syndrome deletion","interstitial duplication 15q autism"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE32563","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE32563","reference_title":"Differential Gene Expression in Angelman syndrome deletion vs. int dup(15) Human Lymphocytes","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"Microarray analysis revealed 1225 genes that were elevated in AS deletion vs int dup(15) and 976 genes that were elevated in int dup(15) vs AS deletion PBMC (pvalue<0.05).","explanation":"Supports this dataset as a human comparative transcriptomic resource connected to UBE3A-region disorders."}],"notes":[],"contexts":[{"id":"disorder:Angelman_Syndrome","name":"Angelman Syndrome","kind":"Disorder","source_path":"kb/disorders/Angelman_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Angelman_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Angelman_Syndrome.html#dataset-geo-gse32563"}],"context_names":["Angelman Syndrome"],"disease_names":["Angelman Syndrome"],"disease_name":"Angelman Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Angelman_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Angelman_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Angelman_Syndrome.html#dataset-geo-gse32563"]},{"id":"dataset:geo:gse326007","accession":"geo:GSE326007","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE326007","title":"Genome-wide analysis of histone H3K18 lactylation in a kainic acid-induced epilepsy model","alternate_titles":[],"description":"Metabolic reprogramming has been increasingly linked to epilepsy, but the epigenetic mechanisms connecting altered glucose metabolism to seizure susceptibility remain incompletely understood. In this study, we aimed to investigate whether lactate-associated histone modification contributes to epileptogenesis and to define its downstream transcriptional targets. Using a kainic acid (KA)-induced temporal lobe epilepsy model, we examined genome-wide chromatin occupancy of histone H3 lysine 18 lactylation (H3K18la) in control and epileptic mouse hippocampal tissues by ChIP-seq.","alternate_descriptions":[],"data_types":["CHIP_SEQ"],"data_type_labels":["Chromatin immunoprecipitation sequencing"],"data_type_label":"Chromatin immunoprecipitation sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42210782"],"publication_contexts":[{"context_id":"disorder:Epilepsy","publication":"PMID:42210782"}],"publication":"PMID:42210782","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42210782","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Epilepsy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Epilepsy","name":"Epilepsy","kind":"Disorder","source_path":"kb/disorders/Epilepsy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Epilepsy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Epilepsy.html#dataset-geo-gse326007"}],"context_names":["Epilepsy"],"disease_names":["Epilepsy"],"disease_name":"Epilepsy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Epilepsy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Epilepsy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Epilepsy.html#dataset-geo-gse326007"]},{"id":"dataset:geo:gse326579","accession":"geo:GSE326579","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE326579","title":"IL-17 Signaling Mediates Inflammation-Induced Capillary Leakage in addition to TNFa","alternate_titles":[],"description":"Capillary leak is a hallmark of acute and chronic inflammatory conditions and represents a critical driver of organ dysfunction and poor clinical outcomes. Despite its clinical relevance, the mechanisms governing endothelial destabilization under inflammatory conditions remain incompletely understood. In this study, we investigated the endothelial response to inflammation using a dynamic human in vitro model, in which human umbilical vein endothelial cells (HUVECs) were cultured in the presence of lipopolysaccharide (LPS)–stimulated human peripheral blood mononuclear cells (PBMCs) to mimic systemic inflammation.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[42],"sample_count":42,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for capillary leak syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:capillary_leak_syndrome","name":"capillary leak syndrome","kind":"Disorder","source_path":"kb/disorders/capillary_leak_syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/capillary_leak_syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/capillary_leak_syndrome.html#dataset-geo-gse326579"}],"context_names":["capillary leak syndrome"],"disease_names":["capillary leak syndrome"],"disease_name":"capillary leak syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/capillary_leak_syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/capillary_leak_syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/capillary_leak_syndrome.html#dataset-geo-gse326579"]},{"id":"dataset:geo:gse327029","accession":"geo:GSE327029","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE327029","title":"KPNA3 drives temozolomide resistance in glioblastoma by upregulating MGMT and activating STAT3 to sustain glioma stem cells","alternate_titles":[],"description":"Glioblastoma (GBM) invariably develops resistance to temozolomide (TMZ), the frontline chemotherapeutic agent, leading to treatment failure. The molecular mechanisms underlying this resistance remain incompletely understood. Here, we identify karyopherin subunit alpha 3 (KPNA3) as a novel and critical driver of TMZ resistance. Through integrated bioinformatics analysis of temozolomide-resistant glioma cells (SF126R) and patient databases, we found KPNA3 expression is elevated in TMZ-resistant contexts and correlates with poor prognosis in TMZ-treated patients.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42295990"],"publication_contexts":[{"context_id":"disorder:Glioma","publication":"PMID:42295990"}],"publication":"PMID:42295990","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42295990","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Glioma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Glioma","name":"Glioma","kind":"Disorder","source_path":"kb/disorders/Glioma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Glioma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Glioma.html#dataset-geo-gse327029"}],"context_names":["Glioma"],"disease_names":["Glioma"],"disease_name":"Glioma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Glioma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Glioma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Glioma.html#dataset-geo-gse327029"]},{"id":"dataset:geo:gse328018","accession":"geo:GSE328018","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE328018","title":"Choroid plexus inflammation in bipolar disorder","alternate_titles":[],"description":"Postmortem human choroid plexus tissue from individuals with bipolar disorder and matched controls was analyzed using cytokine protein arrays and bulk RNA sequencing to characterize immune and barrier-related alterations. The study identifies increased pro-inflammatory signaling and reduced trophic/supportive pathways, implicating the choroid plexus as a neuroimmune interface in bipolar disorder.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[23],"sample_count":23,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41980683"],"publication_contexts":[{"context_id":"disorder:Bipolar_Disorder","publication":"PMID:41980683"}],"publication":"PMID:41980683","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41980683","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Bipolar Disorder (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Bipolar_Disorder","name":"Bipolar Disorder","kind":"Disorder","source_path":"kb/disorders/Bipolar_Disorder.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bipolar_Disorder.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Bipolar_Disorder.html#dataset-geo-gse328018"}],"context_names":["Bipolar Disorder"],"disease_names":["Bipolar Disorder"],"disease_name":"Bipolar Disorder","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Bipolar_Disorder.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bipolar_Disorder.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Bipolar_Disorder.html#dataset-geo-gse328018"]},{"id":"dataset:geo:gse328026","accession":"geo:GSE328026","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE328026","title":"MiT Fusions, TSC1–TSC2 Divergence, and Stem-like Programs Reveal Distinct Origins and Vulnerabilities in PEComa [RNA-seq]","alternate_titles":[],"description":"Perivascular epithelioid cell neoplasms (PEComas) are ultra-rare mesenchymal tumors lacking a molecular classification to guide therapy. Here we perform comprehensive multi-omic profiling of an unselected PEComa cohort. We identify frequent MITF rearrangements involving actin gene partners (ACTA2, ACTG1 and ACTB). Anatomical stratification reveals cyclin-dependent kinase module mutations in gynecologic tumors, whereas soft tissue, gastrointestinal, and pelvic tumors lacked mTOR pathway alterations but are enriched for TFE3/MITF rearrangements.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[69],"sample_count":69,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42331846"],"publication_contexts":[{"context_id":"disorder:Perivascular_Epithelioid_Cell_Neoplasm","publication":"PMID:42331846"}],"publication":"PMID:42331846","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42331846","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Perivascular Epithelioid Cell Neoplasm (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Perivascular_Epithelioid_Cell_Neoplasm","name":"Perivascular Epithelioid Cell Neoplasm","kind":"Disorder","source_path":"kb/disorders/Perivascular_Epithelioid_Cell_Neoplasm.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Perivascular_Epithelioid_Cell_Neoplasm.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Perivascular_Epithelioid_Cell_Neoplasm.html#dataset-geo-gse328026"}],"context_names":["Perivascular Epithelioid Cell Neoplasm"],"disease_names":["Perivascular Epithelioid Cell Neoplasm"],"disease_name":"Perivascular Epithelioid Cell Neoplasm","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Perivascular_Epithelioid_Cell_Neoplasm.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Perivascular_Epithelioid_Cell_Neoplasm.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Perivascular_Epithelioid_Cell_Neoplasm.html#dataset-geo-gse328026"]},{"id":"dataset:geo:gse328136","accession":"geo:GSE328136","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE328136","title":"YKL-40 alleviates the TNF-α-Induced chondrocyte injury in osteoarthritis in vitro","alternate_titles":[],"description":"Background: Osteoarthritis (OA) is a degenerative joint disease with high global prevalence, and YKL-40 is an important factor related to the pathological process of OA. Increased levels of YKL-40 exert a protective influence against TNF-α-induced apoptosis in chondrocytes, thereby enhancing chondrocyte survival and activation, while counteracting TNF-α-driven expression of specific inflammatory mediators such as S100A8/A9.This study aims to evaluate the role and molecular mechanism of YKL-40 on chondrocytes in OA and provide a potential therapeutic avenue requiring further validation.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42045320"],"publication_contexts":[{"context_id":"disorder:Osteoarthritis","publication":"PMID:42045320"}],"publication":"PMID:42045320","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42045320","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Osteoarthritis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. GEO reports Oryctolagus cuniculus; the organism is retained here as source text because this record has no ontology-mapped organism field."],"contexts":[{"id":"disorder:Osteoarthritis","name":"Osteoarthritis","kind":"Disorder","source_path":"kb/disorders/Osteoarthritis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Osteoarthritis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Osteoarthritis.html#dataset-geo-gse328136"}],"context_names":["Osteoarthritis"],"disease_names":["Osteoarthritis"],"disease_name":"Osteoarthritis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Osteoarthritis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Osteoarthritis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Osteoarthritis.html#dataset-geo-gse328136"]},{"id":"dataset:geo:gse328216","accession":"geo:GSE328216","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE328216","title":"NSD2 Degradation Remediates the Oncogenic Cistrome in t(4;14) Multiple Myeloma [RNA-seq]","alternate_titles":[],"description":"The t(4;14) chromosomal translocation drives overexpression of the histone methyltransferase NSD2 and defines a high-risk segment of multiple myeloma (MM) patients. Herein, we report the discovery of NSD2-LDD, a cereblon-recruiting and PWWP1-mediated ligand directed degrader (LDD) that selectively and potently eliminates full length and PWWP1 domain containing NSD2 protein. NSD2-LDD treatment induces global loss of H3K36me2 leading to promoter-proximal spreading of H3K27me3 and re-wiring of cis-regulatory interactions that reverse t(4;14) transcriptional programs.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[24],"sample_count":24,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42371798"],"publication_contexts":[{"context_id":"disorder:Multiple_Myeloma","publication":"PMID:42371798"}],"publication":"PMID:42371798","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42371798","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Multiple Myeloma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Multiple_Myeloma","name":"Multiple Myeloma","kind":"Disorder","source_path":"kb/disorders/Multiple_Myeloma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Multiple_Myeloma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Multiple_Myeloma.html#dataset-geo-gse328216"}],"context_names":["Multiple Myeloma"],"disease_names":["Multiple Myeloma"],"disease_name":"Multiple Myeloma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Multiple_Myeloma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Multiple_Myeloma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Multiple_Myeloma.html#dataset-geo-gse328216"]},{"id":"dataset:geo:gse328265","accession":"geo:GSE328265","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE328265","title":"A CSF Disease-Associated Macrophage Signature defines Progressive Multiple Sclerosis","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[31],"sample_count":31,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42129775"],"publication_contexts":[{"context_id":"disorder:Multiple_Sclerosis","publication":"PMID:42129775"}],"publication":"PMID:42129775","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42129775","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Multiple Sclerosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Multiple_Sclerosis","name":"Multiple Sclerosis","kind":"Disorder","source_path":"kb/disorders/Multiple_Sclerosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Multiple_Sclerosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Multiple_Sclerosis.html#dataset-geo-gse328265"}],"context_names":["Multiple Sclerosis"],"disease_names":["Multiple Sclerosis"],"disease_name":"Multiple Sclerosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Multiple_Sclerosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Multiple_Sclerosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Multiple_Sclerosis.html#dataset-geo-gse328265"]},{"id":"dataset:geo:gse328363","accession":"geo:GSE328363","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE328363","title":"Developmental dynamics of the cortical cellular and molecular landscapes in autism spectrum disorder models","alternate_titles":[],"description":"Recent research has identified over 100 causal genes in autism spectrum disorder (ASD), raising the question of how mutations in genes with diverse functions result in similar clinical presentations. Here, we profiled 251 samples from eleven monogenic ASD mouse models using single-nucleus multi-omic sequencing across three developmental stages, both sexes, and two brain regions. We discovered that, despite wide genetic heterogeneity, ASD-linked mutations converged on perturbations of the radial glial cell lineage. This converging alteration primarily reflects a transient developmental delay rather than a lasting lineage misspecification and resolves by postnatal stages.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[135],"sample_count":135,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42310454"],"publication_contexts":[{"context_id":"disorder:Autism_Spectrum_Disorder","publication":"PMID:42310454"}],"publication":"PMID:42310454","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42310454","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Autism Spectrum Disorder (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Autism_Spectrum_Disorder","name":"Autism Spectrum Disorder","kind":"Disorder","source_path":"kb/disorders/Autism_Spectrum_Disorder.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autism_Spectrum_Disorder.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autism_Spectrum_Disorder.html#dataset-geo-gse328363"}],"context_names":["Autism Spectrum Disorder"],"disease_names":["Autism Spectrum Disorder"],"disease_name":"Autism Spectrum Disorder","same_context_model_ids":["model:kb/disorders/Autism_Spectrum_Disorder.yaml:Genotype-defined patient iPSC-derived neuronal networks","model:kb/disorders/Autism_Spectrum_Disorder.yaml:Multi-genotype human cortical organoid and neural-progenitor panel"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Autism_Spectrum_Disorder.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autism_Spectrum_Disorder.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Autism_Spectrum_Disorder.html#dataset-geo-gse328363"]},{"id":"dataset:geo:gse328399","accession":"geo:GSE328399","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE328399","title":"Neutrophil extracellular traps aggravate COVID-19 related acute macular neuroretinopathy by promoting immune microthrombosis","alternate_titles":[],"description":"To observe retinal and peripheral blood bioinformatic characteristics of COVID-19 infected individuals with or without suffering acute macular neuroretinopathy (AMN)","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Acute Macular Neuroretinopathy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Acute_Macular_Neuroretinopathy","name":"Acute Macular Neuroretinopathy","kind":"Disorder","source_path":"kb/disorders/Acute_Macular_Neuroretinopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Acute_Macular_Neuroretinopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Acute_Macular_Neuroretinopathy.html#dataset-geo-gse328399"}],"context_names":["Acute Macular Neuroretinopathy"],"disease_names":["Acute Macular Neuroretinopathy"],"disease_name":"Acute Macular Neuroretinopathy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Acute_Macular_Neuroretinopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Acute_Macular_Neuroretinopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Acute_Macular_Neuroretinopathy.html#dataset-geo-gse328399"]},{"id":"dataset:geo:gse328831","accession":"geo:GSE328831","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE328831","title":"Bulk RNA-seq of laser-microdissected granuloma and adjacent non-granuloma regions from FFPE lung tissues of pulmonary sarcoidosis","alternate_titles":[],"description":"Sarcoidosis is a systemic granulomatous disease with heterogeneous organ involvement and clinical outcomes. To characterize transcriptional features associated with pulmonary sarcoid granulomas, we performed bulk RNA sequencing of laser-microdissected granuloma regions and adjacent non-granuloma regions from formalin-fixed paraffin-embedded (FFPE) lung tissue specimens obtained from patients with pulmonary sarcoidosis. The dataset includes paired regional samples derived from clinically obtained lung specimens. These data provide a resource for investigating localized gene expression differences associated with granuloma formation in pulmonary sarcoidosis.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[14],"sample_count":14,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Sarcoidosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Sarcoidosis","name":"Sarcoidosis","kind":"Disorder","source_path":"kb/disorders/Sarcoidosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sarcoidosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Sarcoidosis.html#dataset-geo-gse328831"}],"context_names":["Sarcoidosis"],"disease_names":["Sarcoidosis"],"disease_name":"Sarcoidosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Sarcoidosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sarcoidosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Sarcoidosis.html#dataset-geo-gse328831"]},{"id":"dataset:geo:gse329001","accession":"geo:GSE329001","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE329001","title":"LDLR variant classification through activity-normalized prime editing screening","alternate_titles":[],"description":"Pooled activity-normalized prime-editing screen installing 5,184 LDLR coding variants in a human cell line and reading out LDL-cholesterol uptake, with each pegRNA paired to a genotypic outcome reporter so phenotypic scores can be corrected for editing efficiency. Manually relevance-triaged: the series is about the LDLR allelic series itself - which coding change breaks which step of receptor function - which is the axis this entry is built on, not merely about a gene that FH shares with other entries.","alternate_descriptions":[],"data_types":["MULTI_OMICS_PERTURBATION"],"data_type_labels":["Multi Omics Perturbation"],"data_type_label":"Multi Omics Perturbation","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:6547","label":"LDLR","display_label":"LDLR","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/6547"}],"genes":["LDLR"],"platforms":[],"platform":null,"publications":["PMID:42677454"],"publication_contexts":[{"context_id":"disorder:LDLR-Related_Familial_Hypercholesterolemia","publication":"PMID:42677454"}],"publication":"PMID:42677454","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42677454","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE329001","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE329001","reference_title":"LDLR variant classification through activity-normalized prime editing screening","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We developed an innovative, activity-normalized prime editing screening pipeline to measure the impact of 5,184 LDLR coding variants on LDL-cholesterol (LDL-C) uptake.","explanation":"The repository record's own statement of what the series contains, which is what makes it the dataset for the allelic-series axis of this entry."}],"notes":["Surfaced by `just discover-datasets` as a DIRECT candidate and confirmed against the linked publication before inclusion. The evidence item quotes the cached GEO record itself; the screen's scientific findings are cited from the publication on the corresponding experimental model instead."],"contexts":[{"id":"disorder:LDLR-Related_Familial_Hypercholesterolemia","name":"LDLR-Related Familial Hypercholesterolemia","kind":"Disorder","source_path":"kb/disorders/LDLR-Related_Familial_Hypercholesterolemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/LDLR-Related_Familial_Hypercholesterolemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/LDLR-Related_Familial_Hypercholesterolemia.html#dataset-geo-gse329001"}],"context_names":["LDLR-Related Familial Hypercholesterolemia"],"disease_names":["LDLR-Related Familial Hypercholesterolemia"],"disease_name":"LDLR-Related Familial Hypercholesterolemia","same_context_model_ids":["model:kb/disorders/LDLR-Related_Familial_Hypercholesterolemia.yaml:Activity-normalized prime editing saturation screen of LDLR coding variants","model:kb/disorders/LDLR-Related_Familial_Hypercholesterolemia.yaml:CHO-ldlA7 heterologous LDLR variant expression assay","model:kb/disorders/LDLR-Related_Familial_Hypercholesterolemia.yaml:J.D. fibroblast strain (internalization-defective LDLR alleles)","model:kb/disorders/LDLR-Related_Familial_Hypercholesterolemia.yaml:JD iPSC-derived hepatocyte-like cells"],"candidate_model_ids":["model:kb/disorders/LDLR-Related_Familial_Hypercholesterolemia.yaml:Activity-normalized prime editing saturation screen of LDLR coding variants"],"association_basis":"Same publication as a NAM (candidate)","nam_disease_context":"Same publication as a NAM (candidate)","source_paths":["kb/disorders/LDLR-Related_Familial_Hypercholesterolemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/LDLR-Related_Familial_Hypercholesterolemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/LDLR-Related_Familial_Hypercholesterolemia.html#dataset-geo-gse329001"]},{"id":"dataset:geo:gse329070","accession":"geo:GSE329070","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE329070","title":"TCF7L2 Promotes Abdominal Aortic Aneurysm through Smooth Muscle Cell-Mediated Extracellular Matrix Remodeling [RNA-seq]","alternate_titles":[],"description":"Abdominal aortic aneurysm (AAA) lacks effective pharmacological therapies. Here, we investigate transcription factor 7-like 2 (TCF7L2), a genetic locus associated with both thoracic and abdominal aortic aneurysms, to elucidate its role in AAA pathogenesis. Integrating summary-data-based Mendelian randomization (SMR) with single-cell RNA sequencing (scRNA-seq) of human and mouse aortas, we identify TCF7L2 as a gene enriched in vascular smooth muscle cells (VSMCs) and causally linked to AAA development.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[8],"sample_count":8,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42060473"],"publication_contexts":[{"context_id":"disorder:Abdominal_Aortic_Aneurysm","publication":"PMID:42060473"}],"publication":"PMID:42060473","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42060473","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Abdominal Aortic Aneurysm (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Abdominal_Aortic_Aneurysm","name":"Abdominal Aortic Aneurysm","kind":"Disorder","source_path":"kb/disorders/Abdominal_Aortic_Aneurysm.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Abdominal_Aortic_Aneurysm.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Abdominal_Aortic_Aneurysm.html#dataset-geo-gse329070"}],"context_names":["Abdominal Aortic Aneurysm"],"disease_names":["Abdominal Aortic Aneurysm"],"disease_name":"Abdominal Aortic Aneurysm","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Abdominal_Aortic_Aneurysm.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Abdominal_Aortic_Aneurysm.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Abdominal_Aortic_Aneurysm.html#dataset-geo-gse329070"]},{"id":"dataset:geo:gse329156","accession":"geo:GSE329156","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE329156","title":"Modeling Tay-Sachs Disease in Astrocyte-Like Cells Reveals Significant Changes in the Transcriptomic Profile","alternate_titles":[],"description":"RNA-seq study of a Tay-Sachs astrocyte-like cell model. Its six samples describe a cellular transcriptomic experiment; they do not establish human astrocyte state abundance, neuronal injury causality or population prevalence.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["GEO metadata verified on 2026-09-04. No associated peer-reviewed publication was identified in the checked record; no raw-data analysis was performed."],"contexts":[{"id":"disorder:Tay-Sachs_Disease","name":"Tay-Sachs Disease","kind":"Disorder","source_path":"kb/disorders/Tay-Sachs_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Tay-Sachs_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Tay-Sachs_Disease.html#dataset-geo-gse329156"}],"context_names":["Tay-Sachs Disease"],"disease_names":["Tay-Sachs Disease"],"disease_name":"Tay-Sachs Disease","same_context_model_ids":["model:kb/disorders/Tay-Sachs_Disease.yaml:GM2-loaded neuronal cultures","model:kb/disorders/Tay-Sachs_Disease.yaml:Patient-derived GM2 skin fibroblasts","model:kb/disorders/Tay-Sachs_Disease.yaml:Sandhoff cerebral organoids with isogenic correction"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Tay-Sachs_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Tay-Sachs_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Tay-Sachs_Disease.html#dataset-geo-gse329156"]},{"id":"dataset:geo:gse329403","accession":"geo:GSE329403","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE329403","title":"HCN4 gain-of-function mutation increases intrinsic heart rate and limits maladaptive remodeling under pressure overload","alternate_titles":[],"description":"Cardiac RNA sequencing from HCN4(Y527F) knock-in mice, which carry a gain-of-function C-linker mutation that shifts channel activation to more positive potentials. The allele is the mirror image of the SSS2 lesion, and the mice have a higher intrinsic heart rate with no structural cardiomyopathy up to twelve months. It is included here as the opposite-direction control on the same gene: it is the closest available transcriptional readout of altered HCN4 channel availability in myocardium, and it bears on whether the structural arm of SSS2 can be a consequence of the rate change alone.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"house mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42358349"],"publication_contexts":[{"context_id":"disorder:Sick_Sinus_Syndrome_2_Autosomal_Dominant","publication":"PMID:42358349"}],"publication":"PMID:42358349","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42358349","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:42358349","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/42358349","reference_title":"HCN4 gain-of-function mutation increases intrinsic heart rate and limits maladaptive remodeling under pressure overload.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"We generated HCN4(Y527F) knock-in mice (HCN4F) carrying a GOF mutation in the C-linker of HCN4 channels, which shifts their activation curves to more positive potentials.","explanation":"Describes the genotype behind this accession and makes explicit that the direction of effect is opposite to the SSS2 lesion."}],"notes":["Triage note: this is a gain-of-function allele in mouse, not the human loss-of-function lesion of SSS2, and it must not be read as an SSS2 expression dataset. Verified with just verify-datasets."],"contexts":[{"id":"disorder:Sick_Sinus_Syndrome_2_Autosomal_Dominant","name":"Sick Sinus Syndrome 2, Autosomal Dominant","kind":"Disorder","source_path":"kb/disorders/Sick_Sinus_Syndrome_2_Autosomal_Dominant.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sick_Sinus_Syndrome_2_Autosomal_Dominant.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Sick_Sinus_Syndrome_2,_Autosomal_Dominant.html#dataset-geo-gse329403"}],"context_names":["Sick Sinus Syndrome 2, Autosomal Dominant"],"disease_names":["Sick Sinus Syndrome 2, Autosomal Dominant"],"disease_name":"Sick Sinus Syndrome 2, Autosomal Dominant","same_context_model_ids":["model:kb/disorders/Sick_Sinus_Syndrome_2_Autosomal_Dominant.yaml:hiPSC-derived pacemaker cardiomyocytes as a human I_f measurement platform","model:kb/disorders/Sick_Sinus_Syndrome_2_Autosomal_Dominant.yaml:Patient-derived hiPSC lines carrying a heterozygous and a homozygous HCN4 variant (UKMi009-A, UKMi011-A)"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Sick_Sinus_Syndrome_2_Autosomal_Dominant.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sick_Sinus_Syndrome_2_Autosomal_Dominant.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Sick_Sinus_Syndrome_2,_Autosomal_Dominant.html#dataset-geo-gse329403"]},{"id":"dataset:geo:gse329991","accession":"geo:GSE329991","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE329991","title":"An Interferon-gamma-Driven Myeloid Inflammatory Signature defines Glucocorticoid-Resistance of Immune Checkpoint Inhibitor-Associated Myocarditis","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Human single-cell profiling of checkpoint-inhibitor myocarditis, relevant to the ICI-Associated subtype and to the corticosteroid treatment entry. No linked publication was available at the time of curation."],"contexts":[{"id":"disorder:Myocarditis","name":"Myocarditis","kind":"Disorder","source_path":"kb/disorders/Myocarditis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myocarditis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Myocarditis.html#dataset-geo-gse329991"}],"context_names":["Myocarditis"],"disease_names":["Myocarditis"],"disease_name":"Myocarditis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Myocarditis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myocarditis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Myocarditis.html#dataset-geo-gse329991"]},{"id":"dataset:geo:gse330188","accession":"geo:GSE330188","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE330188","title":"Crnic Institute Human Trisome Project - Tofacitinib for Immune Skin Conditions in Down Syndrome: PolyA RNAseq from whole blood","alternate_titles":[],"description":"Analysis of steady-state mRNA levels in whole blood of subjects with Down syndrome (trisomy 21) and qualifying moderate-to-severe immune skin conditions. This dataset is part of the Human Trisome Project run by the Linda Crnic Institute for Down Syndrome at University of Colorado Anschutz. http://www.trisome.org/","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[194],"sample_count":194,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Down syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Down_syndrome","name":"Down_syndrome","kind":"Disorder","source_path":"kb/disorders/Down_syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Down_syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Down_syndrome.html#dataset-geo-gse330188"}],"context_names":["Down_syndrome"],"disease_names":["Down_syndrome"],"disease_name":"Down_syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Down_syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Down_syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Down_syndrome.html#dataset-geo-gse330188"]},{"id":"dataset:geo:gse330200","accession":"geo:GSE330200","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE330200","title":"The p.Ser143Pro lamin A/C mutation leads to dilated cardiomyopathy and activates the unfolded protein response pathway in a knock-in mouse model","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["GEO lists this series under two taxa (Homo sapiens; Mus musculus) for the LMNA p.S143P variant. `organism` is single-valued, so it records the mouse knock-in model the series is titled for; the human samples are not represented by that slot. Carries no linked publication in the GEO index at time of curation, so no evidence block is given."],"contexts":[{"id":"disorder:Dilated_Cardiomyopathy_1A","name":"Dilated Cardiomyopathy 1A","kind":"Disorder","source_path":"kb/disorders/Dilated_Cardiomyopathy_1A.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dilated_Cardiomyopathy_1A.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy_1A.html#dataset-geo-gse330200"}],"context_names":["Dilated Cardiomyopathy 1A"],"disease_names":["Dilated Cardiomyopathy 1A"],"disease_name":"Dilated Cardiomyopathy 1A","same_context_model_ids":["model:kb/disorders/Dilated_Cardiomyopathy_1A.yaml:Patient-derived LMNA-mutant iPSC cardiomyocytes"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Dilated_Cardiomyopathy_1A.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dilated_Cardiomyopathy_1A.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy_1A.html#dataset-geo-gse330200"]},{"id":"dataset:geo:gse330223","accession":"geo:GSE330223","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE330223","title":"Convergence of cytokine dysregulation and antibody deficiency in common variable immunodeficiency with inflammatory complications","alternate_titles":[],"description":"Background: Noninfectious complications are the greatest cause of morbidity and mortality in common variable immunodeficiency (CVID), but their pathogenesis remains poorly defined. Objective: Using high-throughput approaches, we aimed to identify, correlate, and determine the significance of immunologic features of CVID with noninfectious complications (CVIDc). Methods: We simultaneously applied proteomics, RNA sequencing, and mass cytometry to a large cohort with primary antibody deficiency. Results: CVIDc is differentiated from uncomplicated CVID, other forms of primary antibody deficiency, and healthy controls by a distinct plasma proteomic profile.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[42],"sample_count":42,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:34146579"],"publication_contexts":[{"context_id":"disorder:Common_Variable_Immunodeficiency","publication":"PMID:34146579"}],"publication":"PMID:34146579","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34146579","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Common Variable Immunodeficiency (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Common_Variable_Immunodeficiency","name":"Common Variable Immunodeficiency","kind":"Disorder","source_path":"kb/disorders/Common_Variable_Immunodeficiency.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Common_Variable_Immunodeficiency.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Common_Variable_Immunodeficiency.html#dataset-geo-gse330223"}],"context_names":["Common Variable Immunodeficiency"],"disease_names":["Common Variable Immunodeficiency"],"disease_name":"Common Variable Immunodeficiency","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Common_Variable_Immunodeficiency.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Common_Variable_Immunodeficiency.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Common_Variable_Immunodeficiency.html#dataset-geo-gse330223"]},{"id":"dataset:geo:gse330821","accession":"geo:GSE330821","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE330821","title":"THBS1 Induces Dysfunction of Ovarian Granulosa Cells in Patients with Polycystic Ovary Syndrome by Activating the TGF-β/Smad Pathway","alternate_titles":[],"description":"To investigate the role of thrombospondin-1 (THBS1) in polycystic ovary syndrome (PCOS) pathogenesis and its mechanism in regulating granulosa cell (GC) function.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42351701"],"publication_contexts":[{"context_id":"disorder:Polycystic_Ovary_Syndrome","publication":"PMID:42351701"}],"publication":"PMID:42351701","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42351701","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Polycystic Ovary Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Polycystic_Ovary_Syndrome","name":"Polycystic Ovary Syndrome","kind":"Disorder","source_path":"kb/disorders/Polycystic_Ovary_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Polycystic_Ovary_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Polycystic_Ovary_Syndrome.html#dataset-geo-gse330821"}],"context_names":["Polycystic Ovary Syndrome"],"disease_names":["Polycystic Ovary Syndrome"],"disease_name":"Polycystic Ovary Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Polycystic_Ovary_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Polycystic_Ovary_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Polycystic_Ovary_Syndrome.html#dataset-geo-gse330821"]},{"id":"dataset:geo:gse330891","accession":"geo:GSE330891","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE330891","title":"Spatial and cell type specific molecular genetic investigations of inflammatory myopathies with selective perifascicular injury.","alternate_titles":[],"description":"Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of systemic autoimmune disease often with multisystem involvement. Targeted therapy is still lacking. Efficient serum or histological markers to measure disease activity and predict disease course are missing. Perifascicular myofiber atrophy is a hall mark of dermatomyositis (DM). Despite decades of research, the mechanism of perifascicular atrophy is still incompletely understood. Across other IIM subtypes, perifascicular myofiber necrosis is also the hall mark pathology for antisynthetase syndrome associated myositis (ASyS)5, and can be seen in a subset of lupus myositis (LM).","alternate_descriptions":[],"data_types":["SPATIAL_TRANSCRIPTOMICS"],"data_type_labels":["Spatially resolved transcriptomics"],"data_type_label":"Spatially resolved transcriptomics","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[301],"sample_count":301,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42427858"],"publication_contexts":[{"context_id":"disorder:Antisynthetase_Syndrome","publication":"PMID:42427858"}],"publication":"PMID:42427858","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42427858","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Antisynthetase Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Antisynthetase_Syndrome","name":"Antisynthetase Syndrome","kind":"Disorder","source_path":"kb/disorders/Antisynthetase_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Antisynthetase_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Antisynthetase_Syndrome.html#dataset-geo-gse330891"}],"context_names":["Antisynthetase Syndrome"],"disease_names":["Antisynthetase Syndrome"],"disease_name":"Antisynthetase Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Antisynthetase_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Antisynthetase_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Antisynthetase_Syndrome.html#dataset-geo-gse330891"]},{"id":"dataset:geo:gse332819","accession":"geo:GSE332819","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE332819","title":"Longitudinal CITE-seq analysis in juvenile-onset systemic sclerosis monocytes following autologous stem cell transplant","alternate_titles":[],"description":"Juvenile systemic sclerosis (jSSc) is a rare and severe autoimmune disease marked by skin fibrosis and damage to multiple organ systems. This study implements autologous stem cell transplantation (ASCT), a newly available treatment protocol which aims to restore immune homeostasis, in this case amongst jSSc patients. Here, we analyze peripheral blood mononuclear cells (PBMCs) from 3 jSSc patients prior to ASCT and 6, 12, and 24 months post treatment. These samples were then sequenced and tagged with antibodies using cellular indexing of transcriptomes and epitopes (CITE-seq).","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[15],"sample_count":15,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Systemic Sclerosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Systemic_Sclerosis","name":"Systemic Sclerosis","kind":"Disorder","source_path":"kb/disorders/Systemic_Sclerosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Systemic_Sclerosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Systemic_Sclerosis.html#dataset-geo-gse332819"}],"context_names":["Systemic Sclerosis"],"disease_names":["Systemic Sclerosis"],"disease_name":"Systemic Sclerosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Systemic_Sclerosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Systemic_Sclerosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Systemic_Sclerosis.html#dataset-geo-gse332819"]},{"id":"dataset:geo:gse333617","accession":"geo:GSE333617","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE333617","title":"Targeting JAK1/3-STAT1 signaling attenuates cytotoxic T lymphocytes activation for the treatment in Stevens-Johnson syndrome and toxic epidermal necrolysis","alternate_titles":[],"description":"Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening severe cutaneous adverse reactions (SCARs). We integrate single-cell and spatial transcriptomic analyses on blood, blisters, and lesional skin from SJS/TEN patients, revealing IFN-γ and JAK/STAT signaling as the key pathways responsible for driving epidermal necrolysis. We identify JAK1/3–STAT1 signaling as a primary driver of the activation of CD8+ cytotoxic T lymphocytes (CTLs), natural killer (NK)/NKT cells, macrophages and conventional dendritic cells in skin lesions.","alternate_descriptions":[],"data_types":["MULTI_OMICS"],"data_type_labels":["Multi Omics"],"data_type_label":"Multi Omics","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[26],"sample_count":26,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Stevens-Johnson Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Stevens-Johnson_Syndrome","name":"Stevens-Johnson Syndrome","kind":"Disorder","source_path":"kb/disorders/Stevens-Johnson_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Stevens-Johnson_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Stevens-Johnson_Syndrome.html#dataset-geo-gse333617"}],"context_names":["Stevens-Johnson Syndrome"],"disease_names":["Stevens-Johnson Syndrome"],"disease_name":"Stevens-Johnson Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Stevens-Johnson_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Stevens-Johnson_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Stevens-Johnson_Syndrome.html#dataset-geo-gse333617"]},{"id":"dataset:geo:gse333647","accession":"geo:GSE333647","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE333647","title":"m6A modification landscapes of human metapneumovirus, mumps virus, and host A549 cell RNAs revealed by single-base-resolution GLORI-seq [A549 GLORI]","alternate_titles":[],"description":"N6-methyladenosine (m6A) is a common modification on mRNA. Multiple viruses exploit host m6A machinery to modify their own genomic RNA and mRNA, thereby facilitating viral replication and evasion of host innate immune surveillance. In this study, we employed the single-base-resolution high-throughput sequencing technique glyoxal and nitrite-mediated deamination of unmethylated adenosines (GLORI) to identify m6A modification sites on the RNAs of Human metapneumovirus (hMPV, NL/1/00 strain) and Mumps virus (MuV, JL2 strain), as well as to characterize the m6A landscapes of the host cell transcriptome in A549 lung epithelial cells.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Mumps (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Mumps","name":"Mumps","kind":"Disorder","source_path":"kb/disorders/Mumps.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mumps.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Mumps.html#dataset-geo-gse333647"}],"context_names":["Mumps"],"disease_names":["Mumps"],"disease_name":"Mumps","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Mumps.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mumps.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Mumps.html#dataset-geo-gse333647"]},{"id":"dataset:geo:gse333903","accession":"geo:GSE333903","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE333903","title":"Human metapneumovirus and mumps virus alter the m6A landscapes in THP-1-derived immature dendritic cells","alternate_titles":[],"description":"N6-methyladenosine (m6A) is a widespread mRNA modification that regulates RNA metabolism and influences virus-induced immune responses. We performed MeRIP-seq to profile m6A landscapes in THP-1-derived immature dendritic cells (THP-iDCs) before and after infection with Human metapneumovirus (hMPV, NL/00/1) or mumps virus (MuV, JL2). Integration of m6A modifications on key innate immune transcripts with transcriptomic data, together with m6A levels on cellular and viral RNA, revealed a dual role of m6A in viral replication and host immune regulation. These datasets provide a resource for exploring epitranscriptomic regulation during hMPV and MuV infection.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Mumps (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Mumps","name":"Mumps","kind":"Disorder","source_path":"kb/disorders/Mumps.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mumps.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Mumps.html#dataset-geo-gse333903"}],"context_names":["Mumps"],"disease_names":["Mumps"],"disease_name":"Mumps","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Mumps.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mumps.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Mumps.html#dataset-geo-gse333903"]},{"id":"dataset:geo:gse333999","accession":"geo:GSE333999","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE333999","title":"The intracellular domain of the epilepsy protein PCDH19 regulates spine density in cortical neurons in vivo via Xlr genes.","alternate_titles":[],"description":"RNA sequencing of mouse ESC-derived cortical neurons at DIV8 and DIV12, comparing wild-type neurons against neurons overexpressing the cleaved cytoplasmic domain of PCDH19. Addresses a role for protocadherin-19 beyond cell-cell adhesion - nuclear signalling by its intracellular domain - which is a mechanism the entry's pathograph does not currently model.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"house mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:14270","label":"PCDH19","display_label":"PCDH19","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/14270"}],"genes":["PCDH19"],"platforms":[],"platform":null,"publications":["PMID:42303573"],"publication_contexts":[{"context_id":"disorder:PCDH19_Clustering_Epilepsy","publication":"PMID:42303573"}],"publication":"PMID:42303573","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42303573","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Found by a targeted GEO DataSets title search for PCDH19; accession and metadata verified against NCBI E-utilities on 2026-08-27. Title, sample count, and organism are GEO's own values. A gain-of-domain overexpression experiment, not a patient-variant or knockout comparison."],"contexts":[{"id":"disorder:PCDH19_Clustering_Epilepsy","name":"PCDH19 Clustering Epilepsy","kind":"Disorder","source_path":"kb/disorders/PCDH19_Clustering_Epilepsy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/PCDH19_Clustering_Epilepsy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/PCDH19_Clustering_Epilepsy.html#dataset-geo-gse333999"}],"context_names":["PCDH19 Clustering Epilepsy"],"disease_names":["PCDH19 Clustering Epilepsy"],"disease_name":"PCDH19 Clustering Epilepsy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/PCDH19_Clustering_Epilepsy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/PCDH19_Clustering_Epilepsy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/PCDH19_Clustering_Epilepsy.html#dataset-geo-gse333999"]},{"id":"dataset:geo:gse334206","accession":"geo:GSE334206","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE334206","title":"STK25 m6A modification regulates CD4+ T cell glycolysis mediated immune imbalance in systemic lupus erythematosus","alternate_titles":[],"description":"Systemic lupus erythematosus (SLE) is a complex autoimmune disease with an incompletely understood pathogenesis. N6-methyladenosine (m6A) has been implicated in immune regulation and disease progression, yet its role in disrupting immune homeostasis in SLE, particularly in CD4+ T-cell differentiation, remains poorly understood. In the present study, m6A-modified RNA immunoprecipitation sequencing (m6A-seq) and RNA sequencing (RNA-seq) of peripheral blood mononuclear cells from patients with SLE identified serine/threonine protein kinase 25 (STK25) as a candidate gene exhibiting abnormal m6A modification, and its expression was subsequently validated using reverse transcription-quantitative (...","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[20],"sample_count":20,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Systemic Lupus Erythematosus (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Systemic_Lupus_Erythematosus","name":"Systemic Lupus Erythematosus","kind":"Disorder","source_path":"kb/disorders/Systemic_Lupus_Erythematosus.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Systemic_Lupus_Erythematosus.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Systemic_Lupus_Erythematosus.html#dataset-geo-gse334206"}],"context_names":["Systemic Lupus Erythematosus"],"disease_names":["Systemic Lupus Erythematosus"],"disease_name":"Systemic Lupus Erythematosus","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Systemic_Lupus_Erythematosus.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Systemic_Lupus_Erythematosus.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Systemic_Lupus_Erythematosus.html#dataset-geo-gse334206"]},{"id":"dataset:geo:gse334405","accession":"geo:GSE334405","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE334405","title":"cGAS-mediated IFN-I signaling contributes to disease progression in drug-refractory epilepsy","alternate_titles":[],"description":"Epilepsy is a prevalent neurological disease with a third of patients becoming non-responsive to antiepileptic drugs and developing drug-refractory epilepsy (DRE). Here we report that DRE disease progression is contributed by overactive cyclic GMP-AMP synthase (cGAS), a double-stranded DNA sensor that induces type I interferon (IFN-I) signaling. In human DRE microglia, we observe a robust IFN-I signature and the activation of upstream cGAS-STING signaling. Further, in mouse models of Dravet syndrome, a genetic form of DRE, we observe the activation of the cGAS pathway. We show that microglial cGAS can be activated by DNA released from hyperexcitable neurons.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[44],"sample_count":44,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Epilepsy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Epilepsy","name":"Epilepsy","kind":"Disorder","source_path":"kb/disorders/Epilepsy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Epilepsy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Epilepsy.html#dataset-geo-gse334405"}],"context_names":["Epilepsy"],"disease_names":["Epilepsy"],"disease_name":"Epilepsy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Epilepsy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Epilepsy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Epilepsy.html#dataset-geo-gse334405"]},{"id":"dataset:geo:gse335884","accession":"geo:GSE335884","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE335884","title":"Single-cell CITE-seq of peritoneal exudate cells from C57BL/6J mice during acute Toxoplasma gondii infection","alternate_titles":[],"description":"Single-cell immune profiling during acute murine Toxoplasma gondii infection, relevant to the innate-to-adaptive transition modelled in the Interferon-Gamma-Dependent Cell-Autonomous Immune Control node.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[2],"sample_count":2,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40854593"],"publication_contexts":[{"context_id":"disorder:Toxoplasmosis","publication":"PMID:40854593"}],"publication":"PMID:40854593","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40854593","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified via `just discover-datasets Toxoplasmosis` (DIRECT relevance tier) and confirmed with `just verify-datasets`. Model-organism data, so it supports mechanism rather than human phenotype. No evidence block: a bulk-discovered accession has no abstract quote to anchor an evidence item."],"contexts":[{"id":"disorder:Toxoplasmosis","name":"Toxoplasmosis","kind":"Disorder","source_path":"kb/disorders/Toxoplasmosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Toxoplasmosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Toxoplasmosis.html#dataset-geo-gse335884"}],"context_names":["Toxoplasmosis"],"disease_names":["Toxoplasmosis"],"disease_name":"Toxoplasmosis","same_context_model_ids":["model:kb/disorders/Toxoplasmosis.yaml:Human cell culture single-cell transcriptomics of ROP/GRA effector injection","model:kb/disorders/Toxoplasmosis.yaml:Stress-induced bradyzoite differentiation in cell culture"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Toxoplasmosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Toxoplasmosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Toxoplasmosis.html#dataset-geo-gse335884"]},{"id":"dataset:geo:gse336316","accession":"geo:GSE336316","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE336316","title":"Synovial Fluid and Serum MicroRNA Signatures in Equine Osteoarthritis","alternate_titles":[],"description":"The aim of this study was to identify differentially expressed microRNAs (miRNAs) in serum and synovial fluid (SF) samples of control horses and those with osteoarthritis (OA), to identify potential candidates for biomarkers of disease. Total RNA was extracted from serum and SF samples of control (n=4) and OA (n=9) horses, and sequenced. Differential expression analysis, pathway analysis and miRNA target prediction were performed. A group of six miRNAs (eca-miR-199a-3p, eca-miR-148a, eca-miR-99b, eca-miR-146a, eca-miR-423-5p and eca-miR-23b) were selected for validation in an independent cohort (serum, n=46; SF, n=88). The effect of clinical variables on miRNA expression was also assessed.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[26],"sample_count":26,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41303673"],"publication_contexts":[{"context_id":"disorder:Osteoarthritis","publication":"PMID:41303673"}],"publication":"PMID:41303673","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41303673","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Osteoarthritis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. GEO reports Equus caballus; the organism is retained here as source text because this record has no ontology-mapped organism field."],"contexts":[{"id":"disorder:Osteoarthritis","name":"Osteoarthritis","kind":"Disorder","source_path":"kb/disorders/Osteoarthritis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Osteoarthritis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Osteoarthritis.html#dataset-geo-gse336316"}],"context_names":["Osteoarthritis"],"disease_names":["Osteoarthritis"],"disease_name":"Osteoarthritis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Osteoarthritis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Osteoarthritis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Osteoarthritis.html#dataset-geo-gse336316"]},{"id":"dataset:geo:gse336875","accession":"geo:GSE336875","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE336875","title":"Pitx2-associated early-onset glaucoma alters corneal innervation and sensory function in a sex-specific manner [RNA-Seq cornea]","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"house mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[20],"sample_count":20,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Pitx2 mutant mouse cornea, described by its authors as a model of Pitx2-associated developmental glaucoma with anterior segment dysgenesis, ocular hypertension and optic neuropathy -- the ASD Congenital Glaucoma subtype curated here. No linked publication in GEO at the time of curation. Verified against NCBI E-utilities on 2026-08-20."],"contexts":[{"id":"disorder:Congenital_Glaucoma","name":"Congenital Glaucoma","kind":"Disorder","source_path":"kb/disorders/Congenital_Glaucoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Congenital_Glaucoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Congenital_Glaucoma.html#dataset-geo-gse336875"}],"context_names":["Congenital Glaucoma"],"disease_names":["Congenital Glaucoma"],"disease_name":"Congenital Glaucoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Congenital_Glaucoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Congenital_Glaucoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Congenital_Glaucoma.html#dataset-geo-gse336875"]},{"id":"dataset:geo:gse33941","accession":"geo:GSE33941","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE33941","title":"Survival transcriptome in coenzyme Q deficiency syndrome","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[35],"sample_count":35,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:23533218"],"publication_contexts":[{"context_id":"disorder:Primary_Coenzyme_Q10_Deficiency","publication":"PMID:23533218"}],"publication":"PMID:23533218","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/23533218","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Primary Coenzyme Q10 Deficiency (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Primary_Coenzyme_Q10_Deficiency","name":"Primary Coenzyme Q10 Deficiency","kind":"Disorder","source_path":"kb/disorders/Primary_Coenzyme_Q10_Deficiency.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Primary_Coenzyme_Q10_Deficiency.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Primary_Coenzyme_Q10_Deficiency.html#dataset-geo-gse33941"}],"context_names":["Primary Coenzyme Q10 Deficiency"],"disease_names":["Primary Coenzyme Q10 Deficiency"],"disease_name":"Primary Coenzyme Q10 Deficiency","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Primary_Coenzyme_Q10_Deficiency.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Primary_Coenzyme_Q10_Deficiency.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Primary_Coenzyme_Q10_Deficiency.html#dataset-geo-gse33941"]},{"id":"dataset:geo:gse339484","accession":"geo:GSE339484","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE339484","title":"RNA-seq profiling of 14 paired primary and recurrent glioma cases","alternate_titles":[],"description":"Glioma recurrence remains a major clinical challenge and is associated with poor patient outcomes. To characterize transcriptomic alterations associated with tumor recurrence, we performed bulk RNA sequencing on paired primary and recurrent glioma tissue specimens from 14 patients. According to the 2021 World Health Organization (WHO) Classification of Central Nervous System Tumors, glioblastoma is defined as IDH-wildtype (IDH-wt), CNS WHO grade 4. Based on these criteria, 11 paired cases were classified as glioblastoma (IDH-wt, grade 4), while three paired cases with IDH-mutant, grade 3 gliomas were included as a comparison group.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[28],"sample_count":28,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:40658067"],"publication_contexts":[{"context_id":"disorder:Glioma","publication":"PMID:40658067"}],"publication":"PMID:40658067","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/40658067","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Glioma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Glioma","name":"Glioma","kind":"Disorder","source_path":"kb/disorders/Glioma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Glioma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Glioma.html#dataset-geo-gse339484"}],"context_names":["Glioma"],"disease_names":["Glioma"],"disease_name":"Glioma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Glioma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Glioma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Glioma.html#dataset-geo-gse339484"]},{"id":"dataset:geo:gse343646","accession":"geo:GSE343646","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE343646","title":"A Patient-Analog Adamts2 Knock-In Murine Model Reveals Fibroblast-Centered Extracellular Matrix Failure in Dermatosparaxis Ehlers–Danlos Syndrome (dEDS)","alternate_titles":[],"description":"Single-nucleus RNA sequencing and digital pathology of skin from a patient-analog Adamts2 Q226* knock-in mouse, the first genetically faithful (patient-allele) mouse model of dermatosparaxis EDS. Identifies dermal fibroblasts as the cell population most transcriptionally disrupted by ADAMTS2 loss and quantifies collagen architecture defects beyond what the earlier bovine, double-knockout mouse, and sheep models captured.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[4],"sample_count":4,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:218","label":"ADAMTS2","display_label":"ADAMTS2","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/218"}],"genes":["ADAMTS2"],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE343646","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE343646","reference_title":null,"supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"we generated a patient-analog Adamts2Q226*/Q226* knock-in mouse model and used histologic, ultrastructural, biochemical, digital pathology, and single-nucleus transcriptomic approaches to define the consequences of ADAMTS2 loss in skin","explanation":"Establishes the model as carrying the actual patient nonsense allele (Q226*) rather than an engineered null, distinguishing it from the frameshift/deletion alleles in the calf and double-knockout mouse models already in this entry."},{"reference":"GEO:GSE343646","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE343646","reference_title":null,"supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"Single-nucleus RNA sequencing identified fibroblasts as the cell population most strongly affected by Adamts2 deficiency, with coordinated downregulation of collagen, microfibrillar, and other ECM-associated genes.","explanation":"Reports the study's central novel finding -- fibroblasts as the transcriptionally dominant affected cell population -- which is not established by any of the entry's existing animal models."}],"notes":["No associated peer-reviewed publication (PMID) was found for this 2026 GEO deposit at the time of curation; PubMed searches for the study title and the Adamts2 Q226* knock-in allele returned no hits. Cited here as a dataset record per the geo: reference workflow rather than as a full animal_models entry, since AnimalModel.publication requires a PMID. If a manuscript is later published, this dataset and its findings should be promoted to a full animal_models entry with modeled_mechanisms links."],"contexts":[{"id":"disorder:Dermatosparaxis_Ehlers-Danlos_Syndrome","name":"Dermatosparaxis Ehlers-Danlos Syndrome","kind":"Disorder","source_path":"kb/disorders/Dermatosparaxis_Ehlers-Danlos_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dermatosparaxis_Ehlers-Danlos_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Dermatosparaxis_Ehlers-Danlos_Syndrome.html#dataset-geo-gse343646"}],"context_names":["Dermatosparaxis Ehlers-Danlos Syndrome"],"disease_names":["Dermatosparaxis Ehlers-Danlos Syndrome"],"disease_name":"Dermatosparaxis Ehlers-Danlos Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Dermatosparaxis_Ehlers-Danlos_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dermatosparaxis_Ehlers-Danlos_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Dermatosparaxis_Ehlers-Danlos_Syndrome.html#dataset-geo-gse343646"]},{"id":"dataset:geo:gse35180","accession":"geo:GSE35180","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE35180","title":"Effects of diet and Acads genotype on transcriptional response in brain and liver","alternate_titles":[],"description":"Microarray transcriptomics of Acads-deficient versus wild-type mouse brain and liver under high- versus low-fat diet, revealing AMPK/energy-sensing transcriptional rewiring under dietary fat challenge.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:22936979"],"publication_contexts":[{"context_id":"disorder:SCAD_Deficiency","publication":"PMID:22936979"}],"publication":"PMID:22936979","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/22936979","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Organism: mouse (Mus musculus). ABI Mouse Genome Survey microarray."],"contexts":[{"id":"disorder:SCAD_Deficiency","name":"Short-Chain Acyl-CoA Dehydrogenase Deficiency","kind":"Disorder","source_path":"kb/disorders/SCAD_Deficiency.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/SCAD_Deficiency.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Short-Chain_Acyl-CoA_Dehydrogenase_Deficiency.html#dataset-geo-gse35180"}],"context_names":["Short-Chain Acyl-CoA Dehydrogenase Deficiency"],"disease_names":["Short-Chain Acyl-CoA Dehydrogenase Deficiency"],"disease_name":"Short-Chain Acyl-CoA Dehydrogenase Deficiency","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/SCAD_Deficiency.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/SCAD_Deficiency.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Short-Chain_Acyl-CoA_Dehydrogenase_Deficiency.html#dataset-geo-gse35180"]},{"id":"dataset:geo:gse3567","accession":"geo:GSE3567","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE3567","title":"Listeria infection of Caco-2 cells","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[39],"sample_count":39,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:12537547"],"publication_contexts":[{"context_id":"disorder:Listeriosis","publication":"PMID:12537547"}],"publication":"PMID:12537547","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/12537547","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:12537547","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/12537547","reference_title":"A gene-expression program reflecting the innate immune response of cultured intestinal epithelial cells to infection by Listeria monocytogenes.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We have examined the transcriptional response of cultured human intestinal epithelial cells to infection by L. monocytogenes, which replicates in the host cell cytoplasm and spreads from cell to cell using a form of actin-based motility.","explanation":"The linked publication states what was measured in this dataset and in which cells."}],"notes":["Human intestinal epithelial cells infected with L. monocytogenes. Relevant to the intestinal-invasion node. Found through just discover-datasets and triaged as DIRECT by title, then verified against the linked publication."],"contexts":[{"id":"disorder:Listeriosis","name":"Listeriosis","kind":"Disorder","source_path":"kb/disorders/Listeriosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Listeriosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Listeriosis.html#dataset-geo-gse3567"}],"context_names":["Listeriosis"],"disease_names":["Listeriosis"],"disease_name":"Listeriosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Listeriosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Listeriosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Listeriosis.html#dataset-geo-gse3567"]},{"id":"dataset:geo:gse36119","accession":"geo:GSE36119","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE36119","title":"Global gene expression change in the cerebellum of Niemann-Pick disease type C mice with deletion of Ccl3 or Purkinje neuron-specific NPC1 rescue","alternate_titles":[],"description":"Macrophage inflammatory protein 1alpha/CCL3 protein is a known pro-inflammatory cytokine that can mediate chemotaxis of monocytes and promote cell degranulation. Ccl3 gene expression is elevated in the CNS and visceral tissue of many lysosomal storage disorders. The deletion of Ccl3 in a mouse model of Sandhoff disease was reported to result in reduced monocyte-associated pathology in the brain, delayed neurodegeneration, and prolonged health. However, deletion of Ccl3 in a mouse model of Niemann-Pick C disease was dentrimental or neutral instead of beneficial. Prevention of neuronal loss was instead mediated by providing NPC1 to neurons.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[16],"sample_count":16,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:22493001"],"publication_contexts":[{"context_id":"disorder:Niemann_Pick_Disease_Type_C","publication":"PMID:22493001"}],"publication":"PMID:22493001","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/22493001","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Niemann-Pick Disease Type C (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Niemann_Pick_Disease_Type_C","name":"Niemann-Pick Disease Type C","kind":"Disorder","source_path":"kb/disorders/Niemann_Pick_Disease_Type_C.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Niemann_Pick_Disease_Type_C.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Niemann-Pick_Disease_Type_C.html#dataset-geo-gse36119"}],"context_names":["Niemann-Pick Disease Type C"],"disease_names":["Niemann-Pick Disease Type C"],"disease_name":"Niemann-Pick Disease Type C","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Niemann_Pick_Disease_Type_C.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Niemann_Pick_Disease_Type_C.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Niemann-Pick_Disease_Type_C.html#dataset-geo-gse36119"]},{"id":"dataset:geo:gse36335","accession":"geo:GSE36335","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE36335","title":"Distinct tumorigenic pathways within hereditary nonpolyposis colorectal cancer","alternate_titles":[],"description":"FFPE colorectal cancer expression cohort spanning Lynch syndrome, familial colorectal cancer type X (FCCTX), and sporadic CRC, designed to identify hereditary pathway-level differences.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression 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Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Acquired_Thrombotic_Thrombocytopenic_Purpura","name":"Acquired Thrombotic Thrombocytopenic Purpura","kind":"Disorder","source_path":"kb/disorders/Acquired_Thrombotic_Thrombocytopenic_Purpura.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Acquired_Thrombotic_Thrombocytopenic_Purpura.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Acquired_Thrombotic_Thrombocytopenic_Purpura.html#dataset-geo-gse36418"}],"context_names":["Acquired Thrombotic Thrombocytopenic Purpura"],"disease_names":["Acquired Thrombotic Thrombocytopenic Purpura"],"disease_name":"Acquired Thrombotic Thrombocytopenic Purpura","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association 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Transcriptomes of Giardia intestinalis Assemblages A, B and E Using Strand-specific RNA-seq","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"We have performed strand-specific RNA-seq of trophozoites from four different Giardia intestinalis strains (A=WB and AS175, B=GS, E=P15).","explanation":"GEO summary directly supports accession content and parasite-stage context."},{"reference":"PMID:23555231","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/23555231","reference_title":"Transcriptome profiling of Giardia intestinalis using strand-specific RNA-seq.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Four genetically different isolates were studied (WB (AI), AS175 (AII), P15 (E) and GS (B)) using paired-end, strand-specific RNA-seq.","explanation":"PMID abstract corroborates multi-assemblage transcriptomic design relevant to Giardia pathogenesis 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Array"],"platform":"Affymetrix Human Genome U133 Plus 2.0 Array","publications":["PMID:33530940"],"publication_contexts":[{"context_id":"disorder:Campylobacteriosis","publication":"PMID:33530940"}],"publication":"PMID:33530940","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/33530940","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:33530940","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/33530940","reference_title":"Identification of potential biomarkers for abdominal pain in IBS patients by bioinformatics approach.","supports":"SUPPORT","evidence_source":"COMPUTATIONAL","snippet":"METHODS: Gene expression data (GSE36701) was downloaded from Gene Expression Omnibus database.","explanation":"Confirms the GEO accession used for downstream bioinformatic analysis relevant to post-infectious gastrointestinal phenotypes."}],"notes":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE36701","Widely used IBS dataset for biomarker discovery. Key targets identified include EGFR, VEGFA, BCL2L1, CASP9, MMP9, MAPK14."],"contexts":[{"id":"disorder:Campylobacteriosis","name":"Campylobacteriosis","kind":"Disorder","source_path":"kb/disorders/Campylobacteriosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Campylobacteriosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Campylobacteriosis.html#dataset-geo-gse36701"},{"id":"disorder:Irritable_Bowel_Syndrome","name":"Irritable Bowel Syndrome","kind":"Disorder","source_path":"kb/disorders/Irritable_Bowel_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Irritable_Bowel_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Irritable_Bowel_Syndrome.html#dataset-geo-gse36701"}],"context_names":["Campylobacteriosis","Irritable Bowel 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recorded","source_paths":["kb/disorders/Campylobacteriosis.yaml","kb/disorders/Irritable_Bowel_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Campylobacteriosis.yaml","https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Irritable_Bowel_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Campylobacteriosis.html#dataset-geo-gse36701","https://dismech.monarchinitiative.org/pages/disorders/Irritable_Bowel_Syndrome.html#dataset-geo-gse36701"]},{"id":"dataset:geo:gse37567","accession":"geo:GSE37567","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE37567","title":"Methodoligies for identifying lead toxicity","alternate_titles":[],"description":"Human PBMC transcriptomic dataset used to quantify the impact of lead on cytokine production and gene expression in peripheral blood mononuclear cells.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"CL:0000842","label":"mononuclear leukocyte","display_label":"peripheral blood mononuclear cell","url":"http://purl.obolibrary.org/obo/CL_0000842"}],"sample_type_labels":["mononuclear leukocyte"],"sample_counts":[102],"sample_count":102,"conditions":["lead-associated PBMC cytokine and gene-expression profiling"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE37567","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE37567","reference_title":"Methodoligies for identifying lead toxicity","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Quantifying impact of lead on cytokine production and gene expression in PBMCs","explanation":"Supports this dataset as a lead-relevant PBMC transcriptomic resource."}],"notes":[],"contexts":[{"id":"disorder:Lead_Poisoning","name":"Lead Poisoning","kind":"Disorder","source_path":"kb/disorders/Lead_Poisoning.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Lead_Poisoning.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Lead_Poisoning.html#dataset-geo-gse37567"}],"context_names":["Lead Poisoning"],"disease_names":["Lead Poisoning"],"disease_name":"Lead Poisoning","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Lead_Poisoning.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Lead_Poisoning.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Lead_Poisoning.html#dataset-geo-gse37567"]},{"id":"dataset:geo:gse37666","accession":"geo:GSE37666","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE37666","title":"Granulomatous response to Coxiella burnetii, the agent of Q fever: Activation of type I interferon-related genes","alternate_titles":[],"description":"The formation of granulomas is associated with the resolution of Q fever, a zoonosis due to Coxiella burnetii; however the molecular mechanisms of granuloma formation remain poorly understood. We generated human granulomas with peripheral blood mononuclear cells and beads coated with C. burnetii, using BCG extracts as controls. A microarray analysis showed dramatic changes in gene expression in granuloma cells compared with peripheral blood mononuclear cells. About 60% of modulated genes were common to C. burnetii and BCG granulomas including M1-related genes. C.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:25566510"],"publication_contexts":[{"context_id":"disorder:Q_Fever","publication":"PMID:25566510"}],"publication":"PMID:25566510","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/25566510","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Q Fever (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Q_Fever","name":"Q Fever","kind":"Disorder","source_path":"kb/disorders/Q_Fever.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Q_Fever.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Q_Fever.html#dataset-geo-gse37666"}],"context_names":["Q Fever"],"disease_names":["Q Fever"],"disease_name":"Q Fever","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Q_Fever.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Q_Fever.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Q_Fever.html#dataset-geo-gse37666"]},{"id":"dataset:geo:gse38626","accession":"geo:GSE38626","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE38626","title":"Induced pluripotent stem cells from CINCA syndrome patients as a model for dissecting somatic mosaicism and drug discovery","alternate_titles":[],"description":"iPSC lines generated from two CINCA syndrome patients with somatic NLRP3 mosaicism, differentiated into macrophages. 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This is the only dataset located that is both human and restricted to the infantile-onset form, so it is the direct transcriptomic counterpart of this entry's skeletal-myofiber-injury node.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[58],"sample_count":58,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:4065","label":"GAA","display_label":"GAA","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/4065"}],"genes":["GAA"],"platforms":[],"platform":null,"publications":["PMID:22658377"],"publication_contexts":[{"context_id":"disorder:Infantile-Onset_Pompe_Disease","publication":"PMID:22658377"}],"publication":"PMID:22658377","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/22658377","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:22658377","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/22658377","reference_title":"Transcriptional response to GAA deficiency (Pompe disease) in infantile-onset patients.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"we used microarrays to examine gene expression from the muscle of two cohorts of infantile-onset Pompe patients to identify transcriptional differences that may contribute to the disease phenotype","explanation":"Establishes that this dataset profiles muscle from infantile-onset patients specifically, which is what makes it on-topic for this entry rather than for Pompe disease generally."},{"reference":"PMID:22658377","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/22658377","reference_title":"Transcriptional response to GAA deficiency (Pompe disease) in infantile-onset patients.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"infantile-onset Pompe patient muscle had a gene expression pattern characteristic of immature or regenerating muscle, and exhibited many transcriptional markers of inflammation, despite having few overt signs of inflammatory infiltrate","explanation":"Reports the dataset's principal finding, a regenerative and inflammatory transcriptional signature in infantile-onset patient muscle without matching histologic infiltrate."}],"notes":["Discovered via `just discover-datasets Infantile-Onset_Pompe_Disease` as a DIRECT match - the infantile-onset form is named in the dataset's own title - and retained after manual relevance triage. Verified with `just verify-datasets`. Retrieved 2026-09-01."],"contexts":[{"id":"disorder:Infantile-Onset_Pompe_Disease","name":"Infantile-Onset Pompe Disease","kind":"Disorder","source_path":"kb/disorders/Infantile-Onset_Pompe_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Infantile-Onset_Pompe_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Infantile-Onset_Pompe_Disease.html#dataset-geo-gse38680"}],"context_names":["Infantile-Onset Pompe Disease"],"disease_names":["Infantile-Onset Pompe Disease"],"disease_name":"Infantile-Onset Pompe Disease","same_context_model_ids":["model:kb/disorders/Infantile-Onset_Pompe_Disease.yaml:Patient-derived iPSC cardiomyocytes (PD-iCMs)"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Infantile-Onset_Pompe_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Infantile-Onset_Pompe_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Infantile-Onset_Pompe_Disease.html#dataset-geo-gse38680"]},{"id":"dataset:geo:gse39582","accession":"geo:GSE39582","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE39582","title":"Gene expression Classification of Colon Cancer defines six molecular subtypes with distinct clinical, molecular and survival characteristics [Expression]","alternate_titles":[],"description":"Microarray dataset with colorectal cancer and non-tumoral mucosa samples used for molecular classification and outcome studies.","alternate_descriptions":["Large French multicenter cohort (Cartes d'Identité des Tumeurs program) with 566 colon tumor samples and 19 non-tumoral colorectal mucosa samples (585 total) including MSI status annotation. Contains 71 MSI-high and 439 MSS samples, useful for studying Lynch syndrome-associated molecular signatures."],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0001155","label":"colon","display_label":"colon","url":"http://purl.obolibrary.org/obo/UBERON_0001155"}],"sample_type_labels":["colon"],"sample_counts":[462,585],"sample_count":585,"conditions":["colorectal cancer","non-tumoral colonic mucosa","MSI-high colon cancer","MSS colon cancer","non-tumoral colorectal mucosa"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["Affymetrix Human Genome U133 Plus 2.0 Array"],"platform":"Affymetrix Human Genome U133 Plus 2.0 Array","publications":["PMID:23700391"],"publication_contexts":[{"context_id":"disorder:Lynch_Syndrome","publication":"PMID:23700391"}],"publication":"PMID:23700391","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/23700391","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:23700391","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/23700391","reference_title":"Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value.","supports":"SUPPORT","evidence_source":null,"snippet":"566 samples fulfilled RNA quality requirements. Unsupervised consensus hierarchical clustering applied to gene expression data from a discovery subset of 443 CC samples identified six molecular subtypes.","explanation":"This supports the cohort composition and molecular subtype characterization captured in this dataset entry."}],"notes":["Includes 443 colorectal cancer samples and 19 non-tumoral mucosa samples.","Identifies six molecular subtypes with distinct survival outcomes. MSI status allows identification of Lynch-like tumors and study of immune infiltration patterns."],"contexts":[{"id":"disorder:Colon_Adenocarcinoma","name":"Colon Adenocarcinoma","kind":"Disorder","source_path":"kb/disorders/Colon_Adenocarcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Colon_Adenocarcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Colon_Adenocarcinoma.html#dataset-geo-gse39582"},{"id":"disorder:Lynch_Syndrome","name":"Lynch Syndrome","kind":"Disorder","source_path":"kb/disorders/Lynch_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Lynch_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Lynch_Syndrome.html#dataset-geo-gse39582"}],"context_names":["Colon Adenocarcinoma","Lynch Syndrome"],"disease_names":["Colon Adenocarcinoma","Lynch Syndrome"],"disease_name":"Colon Adenocarcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Colon_Adenocarcinoma.yaml","kb/disorders/Lynch_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Colon_Adenocarcinoma.yaml","https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Lynch_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Colon_Adenocarcinoma.html#dataset-geo-gse39582","https://dismech.monarchinitiative.org/pages/disorders/Lynch_Syndrome.html#dataset-geo-gse39582"]},{"id":"dataset:geo:gse40586","accession":"geo:GSE40586","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE40586","title":"Peripheral blood RNA gene expression profiling in patients with bacterial meningitis","alternate_titles":[],"description":"The aim of present study was to describe the genetic pathways activated during the community acquired bacterial meningitis (BM) by using genome-wide RNA expression profiling combined with functional annotation of transcriptional changes. We included 21 patients with BM hospitalized in 2008. The control group consisted of 18 healthy subjects. The RNA was extracted from whole blood, globin mRNA was depleted and gene expression profiling was performed with GeneChip Human Gene 1.0 ST Arrays enabling the analysis of 28,869 genes. Gene expression profile data were analyzed using Bioconductor packages and Bayesian modeling.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[39],"sample_count":39,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:23515576"],"publication_contexts":[{"context_id":"disorder:Bacterial_meningitis","publication":"PMID:23515576"}],"publication":"PMID:23515576","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/23515576","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Bacterial meningitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Bacterial_meningitis","name":"Bacterial meningitis","kind":"Disorder","source_path":"kb/disorders/Bacterial_meningitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bacterial_meningitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Bacterial_meningitis.html#dataset-geo-gse40586"}],"context_names":["Bacterial meningitis"],"disease_names":["Bacterial meningitis"],"disease_name":"Bacterial meningitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Bacterial_meningitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bacterial_meningitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Bacterial_meningitis.html#dataset-geo-gse40586"]},{"id":"dataset:geo:gse4060","accession":"geo:GSE4060","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE4060","title":"Transcriptome of GIP- and ACTH-dependent Cushing's syndrome.","alternate_titles":[],"description":"Abstract submitted to the Journal of clinical encodcrinology and metabolism: The molecular mechanisms responsible for the ectopic expression of the GIP receptor in the adrenal cortex of patients with GIP-dependent Cushing’s syndrome (CS) are unknown. Chronic adrenal stimulation by ACTH in Cushing’s disease (CD) or by GIP in GIP-dependent AIMAH both lead to induction of a set of genes which stimulate adrenal proliferation and steroidogenesis.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[14],"sample_count":14,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:16772347"],"publication_contexts":[{"context_id":"disorder:Cushings_Syndrome","publication":"PMID:16772347"}],"publication":"PMID:16772347","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/16772347","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Cushing's Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Cushings_Syndrome","name":"Cushing's Syndrome","kind":"Disorder","source_path":"kb/disorders/Cushings_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cushings_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cushing's_Syndrome.html#dataset-geo-gse4060"}],"context_names":["Cushing's Syndrome"],"disease_names":["Cushing's Syndrome"],"disease_name":"Cushing's Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cushings_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cushings_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cushing's_Syndrome.html#dataset-geo-gse4060"]},{"id":"dataset:geo:gse41744","accession":"geo:GSE41744","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE41744","title":"Ficolin-1 is upregulated in leukocytes and glomeruli from microscopic polyangiitis patients","alternate_titles":[],"description":"To search for new markers of active lesions that might help better understand the molecular basis of MPA and aid in its diagnosis, DNA microarray analysis was performed with peripheral blood mononuclear cells (PBMCs).","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:23944633"],"publication_contexts":[{"context_id":"disorder:Microscopic_Polyangiitis","publication":"PMID:23944633"}],"publication":"PMID:23944633","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/23944633","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Microscopic Polyangiitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Microscopic_Polyangiitis","name":"Microscopic Polyangiitis","kind":"Disorder","source_path":"kb/disorders/Microscopic_Polyangiitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Microscopic_Polyangiitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Microscopic_Polyangiitis.html#dataset-geo-gse41744"}],"context_names":["Microscopic Polyangiitis"],"disease_names":["Microscopic Polyangiitis"],"disease_name":"Microscopic Polyangiitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Microscopic_Polyangiitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Microscopic_Polyangiitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Microscopic_Polyangiitis.html#dataset-geo-gse41744"]},{"id":"dataset:geo:gse42352","accession":"geo:GSE42352","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE42352","title":"Genome-wide gene expression profiling of mesenchymal stem cells, osteosarcoma cells, and osteosarcoma cell lines.","alternate_titles":[],"description":"Microarray dataset of osteosarcoma and normal bone samples used for differential expression analyses.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0001474","label":"bone element","display_label":"bone element","url":"http://purl.obolibrary.org/obo/UBERON_0001474"}],"sample_type_labels":["bone element"],"sample_counts":[118],"sample_count":118,"conditions":["osteosarcoma","normal bone tissue"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Includes 103 osteosarcoma samples and 15 normal tissue samples."],"contexts":[{"id":"disorder:Osteosarcoma","name":"Osteosarcoma","kind":"Disorder","source_path":"kb/disorders/Osteosarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Osteosarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Osteosarcoma.html#dataset-geo-gse42352"}],"context_names":["Osteosarcoma"],"disease_names":["Osteosarcoma"],"disease_name":"Osteosarcoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Osteosarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Osteosarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Osteosarcoma.html#dataset-geo-gse42352"]},{"id":"dataset:geo:gse43553","accession":"geo:GSE43553","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE43553","title":"Microarray-based gene expression profiling in patients with cryopyrin-associated periodic syndromes defines a disease-related signature and IL-1-responsive transcripts","alternate_titles":[],"description":"Gene expression microarray profiling of 16 CAPS patients before and after anakinra treatment, compared to healthy controls. Defines a CAPS-specific gene expression signature including transcripts related to innate and adaptive immune responses, oxidative stress, cell death, and cell adhesion.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0000178","label":"blood","display_label":"blood","url":"http://purl.obolibrary.org/obo/UBERON_0000178"}],"sample_type_labels":["blood"],"sample_counts":[100],"sample_count":100,"conditions":["CAPS patients pre-treatment","CAPS patients post-anakinra","healthy controls"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE43553","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE43553","reference_title":"Microarray-based gene expression profiling in patients with cryopyrin-associated periodic syndromes defines a disease-related signature and IL-1-responsive transcripts.","supports":"SUPPORT","evidence_source":null,"snippet":"We identified a gene expression signature that clearly distinguished CAPS patients from controls. A number of DEG were in common with other systemic inflammatory diseases such as systemic onset juvenile idiopathic arthritis.","explanation":"Defines a CAPS-specific transcriptomic signature and identifies IL-1-responsive genes, relevant to understanding the molecular pathology of CINCA/NOMID."}],"notes":[],"contexts":[{"id":"disorder:CINCA_Syndrome","name":"CINCA Syndrome","kind":"Disorder","source_path":"kb/disorders/CINCA_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/CINCA_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/CINCA_Syndrome.html#dataset-geo-gse43553"}],"context_names":["CINCA Syndrome"],"disease_names":["CINCA Syndrome"],"disease_name":"CINCA Syndrome","same_context_model_ids":["model:kb/disorders/CINCA_Syndrome.yaml:CINCA patient iPSC-derived macrophage model of NLRP3 mosaicism"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/CINCA_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/CINCA_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/CINCA_Syndrome.html#dataset-geo-gse43553"]},{"id":"dataset:geo:gse43996","accession":"geo:GSE43996","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE43996","title":"Gene expression profiles of fibroblasts and induced pluripotent stem cells (iPSCs) from individuals with Zellweger spectrum disorder (ZSD), a class of peroxisome biogenesis disorder, and healthy controls","alternate_titles":[],"description":"Zellweger spectrum disorder (PBD-ZSD) is a disease continuum caused by mutations in a subset of PEX genes required for normal peroxisome assembly and function. Their clinical manifestations highlight the importance of peroxisomes in the development and functions of the central nervous system, liver, and other organs. We reprogrammed skin fibroblasts from PBD-ZSD patients into induced pluripotent stem cells (iPSCs) and report their gene expression profiles as well as those of matching healthy controls.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[35],"sample_count":35,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Peroxisome Biogenesis Disorder (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Peroxisome_Biogenesis_Disorder","name":"Peroxisome Biogenesis Disorder","kind":"Disorder","source_path":"kb/disorders/Peroxisome_Biogenesis_Disorder.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Peroxisome_Biogenesis_Disorder.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Peroxisome_Biogenesis_Disorder.html#dataset-geo-gse43996"}],"context_names":["Peroxisome Biogenesis Disorder"],"disease_names":["Peroxisome Biogenesis Disorder"],"disease_name":"Peroxisome Biogenesis Disorder","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Peroxisome_Biogenesis_Disorder.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Peroxisome_Biogenesis_Disorder.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Peroxisome_Biogenesis_Disorder.html#dataset-geo-gse43996"]},{"id":"dataset:geo:gse45050","accession":"geo:GSE45050","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE45050","title":"Expression data from human hepatocellular carcinoma (HCC), Cirrhosis, and non-tumor liver tissues.","alternate_titles":[],"description":"There are significant differences in the expression of genes that regulate metabolic pathways in HCC as compared to Cirrhosis or non-tumor liver tissues. These charcteristic pathways can be exploited for metabolic imaging biomarkers of HCC. We used microarrays to perform genome-wide association study expression in human Grade III hepatocellular carcinoma and surrounding tissues.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[16],"sample_count":16,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:24497316"],"publication_contexts":[{"context_id":"disorder:Liver_Cirrhosis","publication":"PMID:24497316"}],"publication":"PMID:24497316","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/24497316","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Liver Cirrhosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Liver_Cirrhosis","name":"Liver Cirrhosis","kind":"Disorder","source_path":"kb/disorders/Liver_Cirrhosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Liver_Cirrhosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Liver_Cirrhosis.html#dataset-geo-gse45050"}],"context_names":["Liver Cirrhosis"],"disease_names":["Liver Cirrhosis"],"disease_name":"Liver Cirrhosis","same_context_model_ids":["model:kb/disorders/Liver_Cirrhosis.yaml:Akura Twin 384-well liver fibrosis microphysiological system (HepaRG/THP-1 and hTERT-HSC microtissues)"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Liver_Cirrhosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Liver_Cirrhosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Liver_Cirrhosis.html#dataset-geo-gse45050"]},{"id":"dataset:geo:gse46295","accession":"geo:GSE46295","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE46295","title":"Effects of a Tricaprylin Emulsion on Anti-glomerular Basement Membrane Glomerulonephritis in Rats","alternate_titles":[],"description":"Expression data from rat with anti-glomerular basement membrane nephritis (anti-GBM). We used microarrays to analyze the transcriptome of kidney from anti-GBM model rat with or without drug treatment","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:10116","label":"Rattus norvegicus","display_label":"rat","url":"http://purl.obolibrary.org/obo/NCBITaxon_10116"}],"organism_labels":["Rattus norvegicus"],"organism_label":"Rattus norvegicus","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:26235580"],"publication_contexts":[{"context_id":"disorder:Anti-GBM_Disease","publication":"PMID:26235580"}],"publication":"PMID:26235580","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/26235580","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Anti-Glomerular Basement Membrane Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Anti-GBM_Disease","name":"Anti-Glomerular Basement Membrane Disease","kind":"Disorder","source_path":"kb/disorders/Anti-GBM_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Anti-GBM_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Anti-Glomerular_Basement_Membrane_Disease.html#dataset-geo-gse46295"}],"context_names":["Anti-Glomerular Basement Membrane Disease"],"disease_names":["Anti-Glomerular Basement Membrane Disease"],"disease_name":"Anti-Glomerular Basement Membrane Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Anti-GBM_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Anti-GBM_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Anti-Glomerular_Basement_Membrane_Disease.html#dataset-geo-gse46295"]},{"id":"dataset:geo:gse46348","accession":"geo:GSE46348","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE46348","title":"Illumina SNP array data for Brugdata syndrome patients in Taiwan","alternate_titles":[],"description":"Background Brugada syndrome (BrS) is a rare inherited disease causing sudden cardiac death (SCD). Copy number variants (CNVs) can contribute to disease susceptibility, but their role in Brugada syndrome (BrS) is unknown. We aimed to identify a CNV associated with BrS and elucidated its clinical implications. Methods We enrolled 335 unrelated BrS patients from 2000 to 2018 in the Taiwanese population. Microarray and exome sequencing were used for discovery phase whereas Sanger sequencing was used for the validation phase. HEK cells and zebrafish were used to characterize the function of the CNV variant.","alternate_descriptions":[],"data_types":["GWAS"],"data_type_labels":["Genome-wide association study"],"data_type_label":"Genome-wide association study","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[16],"sample_count":16,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:32645615"],"publication_contexts":[{"context_id":"disorder:Brugada_Syndrome","publication":"PMID:32645615"}],"publication":"PMID:32645615","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32645615","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Brugada syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Brugada_Syndrome","name":"Brugada syndrome","kind":"Disorder","source_path":"kb/disorders/Brugada_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Brugada_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Brugada_syndrome.html#dataset-geo-gse46348"}],"context_names":["Brugada syndrome"],"disease_names":["Brugada syndrome"],"disease_name":"Brugada syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Brugada_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Brugada_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Brugada_syndrome.html#dataset-geo-gse46348"]},{"id":"dataset:geo:gse47394","accession":"geo:GSE47394","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE47394","title":"Global gene expression analysis of amniotic fluid cell-free RNA from recipient twins with twin-twin transfusion syndrome","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[26],"sample_count":26,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:23640821"],"publication_contexts":[{"context_id":"disorder:Twin_to_Twin_Transfusion_Syndrome","publication":"PMID:23640821"}],"publication":"PMID:23640821","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/23640821","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Twin to Twin Transfusion Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Twin_to_Twin_Transfusion_Syndrome","name":"Twin to Twin Transfusion Syndrome","kind":"Disorder","source_path":"kb/disorders/Twin_to_Twin_Transfusion_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Twin_to_Twin_Transfusion_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Twin_to_Twin_Transfusion_Syndrome.html#dataset-geo-gse47394"}],"context_names":["Twin to Twin Transfusion Syndrome"],"disease_names":["Twin to Twin Transfusion Syndrome"],"disease_name":"Twin to Twin Transfusion Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Twin_to_Twin_Transfusion_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Twin_to_Twin_Transfusion_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Twin_to_Twin_Transfusion_Syndrome.html#dataset-geo-gse47394"]},{"id":"dataset:geo:gse47642","accession":"geo:GSE47642","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE47642","title":"Kindler syndrome microarray study","alternate_titles":[],"description":"Human skin-biopsy microarray dataset comparing Kindler syndrome and control samples to define transcriptional changes associated with FERMT1 deficiency.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":["Kindler syndrome skin biopsies","normal human skin biopsies"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:24681597"],"publication_contexts":[{"context_id":"disorder:Kindler_Epidermolysis_Bullosa","publication":"PMID:24681597"}],"publication":"PMID:24681597","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/24681597","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE47642","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE47642","reference_title":"Kindler syndrome microarray study","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"Characterization of gene expression profile of normal human and Kindler Syndrome (KS) patients skin biopsies samples","explanation":"Confirms the dataset contains direct human tissue expression profiles from Kindler syndrome and control skin."},{"reference":"GEO:GSE47642","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE47642","reference_title":"Kindler syndrome microarray study","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"to extend the knowledge of transcriptional changes in the Kindler syndrome disease.","explanation":"Supports this dataset as a disease-relevant transcriptomic resource for Kindler EB."}],"notes":[],"contexts":[{"id":"disorder:Kindler_Epidermolysis_Bullosa","name":"Kindler Epidermolysis Bullosa","kind":"Disorder","source_path":"kb/disorders/Kindler_Epidermolysis_Bullosa.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Kindler_Epidermolysis_Bullosa.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Kindler_Epidermolysis_Bullosa.html#dataset-geo-gse47642"}],"context_names":["Kindler Epidermolysis Bullosa"],"disease_names":["Kindler Epidermolysis Bullosa"],"disease_name":"Kindler Epidermolysis Bullosa","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Kindler_Epidermolysis_Bullosa.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Kindler_Epidermolysis_Bullosa.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Kindler_Epidermolysis_Bullosa.html#dataset-geo-gse47642"]},{"id":"dataset:geo:gse48310","accession":"geo:GSE48310","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE48310","title":"Gene Expression in Whole Blood of Atopic Eczema and Healthy Children at 4 years","alternate_titles":[],"description":"We studied genes that are related to atopic diseases [i.e., atopic eczema (AE)]. Immunological factors and principal genes involved in the biosynthesis of polyunsaturated fatty acids were included. We analyzed whether expression of genes encoding key enzymes of LC-PUFA synthesis (FADS1, FADS2 and ELOVL5) is associated with circulating LC-PUFA levels and risk of AE in 4-year-old children. AE (n=20) and non-AE (n=104) children participating in the Sabadell cohort within the INfancia y Medio Ambiente (INMA) Project were included in the present study. RT-PCR with TaqMan Low-Density Array cards was used to measure the expression of these genes.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[124],"sample_count":124,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:24167612"],"publication_contexts":[{"context_id":"disorder:Atopic_Dermatitis","publication":"PMID:24167612"}],"publication":"PMID:24167612","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/24167612","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Atopic Dermatitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Atopic_Dermatitis","name":"Atopic Dermatitis","kind":"Disorder","source_path":"kb/disorders/Atopic_Dermatitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Atopic_Dermatitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Atopic_Dermatitis.html#dataset-geo-gse48310"}],"context_names":["Atopic Dermatitis"],"disease_names":["Atopic Dermatitis"],"disease_name":"Atopic Dermatitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Atopic_Dermatitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Atopic_Dermatitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Atopic_Dermatitis.html#dataset-geo-gse48310"]},{"id":"dataset:geo:gse48459","accession":"geo:GSE48459","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE48459","title":"Sarcoptes scabiei Mites Modulate Gene Expression In Human Skin Equivalents","alternate_titles":[],"description":"The purpose of this study was to identify genes in keratinocytes and fibroblasts in human skin equivalents that changed expression in response to the burrowing of live scabies mites.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[14],"sample_count":14,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:23940705"],"publication_contexts":[{"context_id":"disorder:Scabies","publication":"PMID:23940705"}],"publication":"PMID:23940705","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/23940705","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Scabies (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Scabies","name":"Scabies","kind":"Disorder","source_path":"kb/disorders/Scabies.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Scabies.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Scabies.html#dataset-geo-gse48459"}],"context_names":["Scabies"],"disease_names":["Scabies"],"disease_name":"Scabies","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Scabies.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Scabies.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Scabies.html#dataset-geo-gse48459"]},{"id":"dataset:geo:gse49045","accession":"geo:GSE49045","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE49045","title":"Genome-wide SNP analysis of the Systemic Capillary Leak Syndrome (Clarkson disease)","alternate_titles":[],"description":"The Systemic Capillary Leak Syndrome (SCLS) is an extremely rare, orphan disease that resembles systemic anaphylaxis. The disorder is characterized by repeated, transient, and seemingly unprovoked episodes of hypotensive shock and peripheral edema due to transient endothelial hyperpermeability. SCLS is often accompanied by a monoclonal gammopathy of unknown significance (MGUS). Using Affymetrix Single Nucleotide Polymorphism (SNP) microarrays, we performed the first genome-wide SNP analysis of SCLS in a cohort of 12 disease subjects and 18 controls.","alternate_descriptions":[],"data_types":["GWAS"],"data_type_labels":["Genome-wide association study"],"data_type_label":"Genome-wide association study","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[30],"sample_count":30,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for capillary leak syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:capillary_leak_syndrome","name":"capillary leak syndrome","kind":"Disorder","source_path":"kb/disorders/capillary_leak_syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/capillary_leak_syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/capillary_leak_syndrome.html#dataset-geo-gse49045"}],"context_names":["capillary leak syndrome"],"disease_names":["capillary leak syndrome"],"disease_name":"capillary leak syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/capillary_leak_syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/capillary_leak_syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/capillary_leak_syndrome.html#dataset-geo-gse49045"]},{"id":"dataset:geo:gse49122","accession":"geo:GSE49122","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE49122","title":"Otitis Media Impact on Inner Ear","alternate_titles":[],"description":"Microarray gene expression profiling comparing inner ear tissue from untreated control mice and mice receiving trans-tympanic injection of heat-killed Hemophilus influenzae. Identified 886 genes with significant expression changes in the inner ear (599 upregulated, 287 downregulated), demonstrating that the inner ear mounts a distinct inflammatory response to otitis media independent of the middle ear response. Relevant to understanding the molecular mechanisms of serous labyrinthitis complicating otitis media.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[{"id":null,"label":"Inner ear tissue","display_label":"Inner ear tissue","url":null}],"sample_type_labels":["Inner ear tissue"],"sample_counts":[],"sample_count":null,"conditions":["Otitis media","Inner ear inflammation"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":[],"contexts":[{"id":"disorder:Labyrinthitis","name":"Labyrinthitis","kind":"Disorder","source_path":"kb/disorders/Labyrinthitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Labyrinthitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Labyrinthitis.html#dataset-geo-gse49122"}],"context_names":["Labyrinthitis"],"disease_names":["Labyrinthitis"],"disease_name":"Labyrinthitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Labyrinthitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Labyrinthitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Labyrinthitis.html#dataset-geo-gse49122"]},{"id":"dataset:geo:gse49145","accession":"geo:GSE49145","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE49145","title":"Expression data from homozygous deletion of the Lgi1 gene in murine neural precursor-like cells","alternate_titles":[],"description":"Gene-expression microarray resource comparing Large-T-antigen-immortalized neural precursor-like cultures from E13.5 Lgi1-null and wild-type mice. It is a complete-loss developmental cell model, not a patient cohort or a direct auditory-seizure assay.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"Mus musculus","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["Affymetrix GeneChip Mouse Gene 1.0 ST Array"],"platform":"Affymetrix GeneChip Mouse Gene 1.0 ST Array","publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE49145","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE49145","reference_title":"Expression data from homozygous deletion of the Lgi1 gene in murine neural precursor-like cells","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"we first generated and immortalized neural precursor-like cells (NPC), isolated from Lgi1 null and wild type mice at E13.5 stage using Large-T antigen.","explanation":"Repository description identifies the biological material and perturbation; no patient phenotype or causal migration result is inferred."}],"notes":["Accession, organism and six-sample metadata verified against GEO on 2026-09-21 through the sanctioned reference fetcher. The dataset summary proposes migration and synapse effects; those are not promoted into an established human causal branch without primary experimental adjudication."],"contexts":[{"id":"disorder:Autosomal_Dominant_Epilepsy_with_Auditory_Features","name":"Autosomal Dominant Epilepsy with Auditory Features","kind":"Disorder","source_path":"kb/disorders/Autosomal_Dominant_Epilepsy_with_Auditory_Features.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autosomal_Dominant_Epilepsy_with_Auditory_Features.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Dominant_Epilepsy_with_Auditory_Features.html#dataset-geo-gse49145"}],"context_names":["Autosomal Dominant Epilepsy with Auditory Features"],"disease_names":["Autosomal Dominant Epilepsy with Auditory Features"],"disease_name":"Autosomal Dominant Epilepsy with Auditory Features","same_context_model_ids":["model:kb/disorders/Autosomal_Dominant_Epilepsy_with_Auditory_Features.yaml:Excised intact Lgi1-null hippocampus","model:kb/disorders/Autosomal_Dominant_Epilepsy_with_Auditory_Features.yaml:LGI1 variant secretion and receptor-binding cell assays","model:kb/disorders/Autosomal_Dominant_Epilepsy_with_Auditory_Features.yaml:Lgi1-null acute hippocampal slices","model:kb/disorders/Autosomal_Dominant_Epilepsy_with_Auditory_Features.yaml:Local LGI1 restoration in organotypic hippocampal culture","model:kb/disorders/Autosomal_Dominant_Epilepsy_with_Auditory_Features.yaml:MICAL1 transfected-cell activity and morphology assays","model:kb/disorders/Autosomal_Dominant_Epilepsy_with_Auditory_Features.yaml:Mutant reelin trafficking and autophagy cell assays"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Autosomal_Dominant_Epilepsy_with_Auditory_Features.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autosomal_Dominant_Epilepsy_with_Auditory_Features.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Dominant_Epilepsy_with_Auditory_Features.html#dataset-geo-gse49145"]},{"id":"dataset:geo:gse49659","accession":"geo:GSE49659","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE49659","title":"Retinal Gene and Protein Expression Associated with CNTF-Induced Deconstruction of Photoreceptor Outer Segments in normal and CNGB3-achromatopsia dogs","alternate_titles":[],"description":"Background: Intravitreal injection of CNTF leads to deconstruction and regeneration of photoreceptor outer segments in normal dogs, and improves the success rate of viral CNGB3 gene replacement therapy in dogs (> 1 year) with CNGB3-achromatopsia. Objectives: The goal of this study was to examine the changes caused by intravitreal CNTF injection to the retinal gene expression profiles and the retinal function of normal and CNGB3-achromatopsia affected dogs. Retinal gene expression profiles were evaluated with canine specific Agilent Oligo Microarray containing 42,034 60-mer oligonucleotide probes.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[20],"sample_count":20,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Achromatopsia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Achromatopsia","name":"Achromatopsia","kind":"Disorder","source_path":"kb/disorders/Achromatopsia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Achromatopsia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Achromatopsia.html#dataset-geo-gse49659"}],"context_names":["Achromatopsia"],"disease_names":["Achromatopsia"],"disease_name":"Achromatopsia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Achromatopsia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Achromatopsia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Achromatopsia.html#dataset-geo-gse49659"]},{"id":"dataset:geo:gse52093","accession":"geo:GSE52093","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE52093","title":"Genome-wide analysis of gene expression of ascending aorta from patients with acute Stanford type A aortic dissection","alternate_titles":[],"description":"Gene expression profiling comparing dissected ascending aorta tissue from acute Stanford type A aortic dissection patients to normal aorta controls, identifying pathogenesis pathways.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0001496","label":"ascending aorta","display_label":"ascending aorta","url":"http://purl.obolibrary.org/obo/UBERON_0001496"}],"sample_type_labels":["ascending aorta"],"sample_counts":[12],"sample_count":12,"conditions":["acute aortic dissection","normal aorta control"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["Illumina HumanHT-12 V4.0 expression beadchip"],"platform":"Illumina HumanHT-12 V4.0 expression beadchip","publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identifies genes with altered expression in aortic dissection, providing insights into pathogenesis relevant to Marfan syndrome cardiovascular complications"],"contexts":[{"id":"disorder:Marfan_Syndrome","name":"Marfan Syndrome","kind":"Disorder","source_path":"kb/disorders/Marfan_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Marfan_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Marfan_Syndrome.html#dataset-geo-gse52093"}],"context_names":["Marfan Syndrome"],"disease_names":["Marfan Syndrome"],"disease_name":"Marfan Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Marfan_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Marfan_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Marfan_Syndrome.html#dataset-geo-gse52093"]},{"id":"dataset:geo:gse52222","accession":"geo:GSE52222","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE52222","title":"Aberrant methylation of gene associated CpG sites occurs in borderline personality disorder","alternate_titles":[],"description":"Borderline personality disorder (BPD) is a complex psychiatric disease with an increased impact in the last years. While the diagnosis and therapy are well established, little is known on the pathogenesis of borderline personality disorder. Previously, a significant increase in DNA methylation of relevant neuropsychiatric genes in BPD patients has been reported. In our study we performed genome wide methylation analysis and revealed specific CpG sites that exhibited increased methylation in 26 BPD patients compared to 11 healthy controls.","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[36],"sample_count":36,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:24367640"],"publication_contexts":[{"context_id":"disorder:Borderline_Personality_Disorder","publication":"PMID:24367640"}],"publication":"PMID:24367640","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/24367640","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Borderline Personality Disorder (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Borderline_Personality_Disorder","name":"Borderline Personality Disorder","kind":"Disorder","source_path":"kb/disorders/Borderline_Personality_Disorder.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Borderline_Personality_Disorder.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Borderline_Personality_Disorder.html#dataset-geo-gse52222"}],"context_names":["Borderline Personality Disorder"],"disease_names":["Borderline Personality Disorder"],"disease_name":"Borderline Personality Disorder","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Borderline_Personality_Disorder.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Borderline_Personality_Disorder.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Borderline_Personality_Disorder.html#dataset-geo-gse52222"]},{"id":"dataset:geo:gse52474","accession":"geo:GSE52474","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE52474","title":"Late Multiple Organ Surge in Interferon-regulated Target Genes Characterizes Staphylococcal Enterotoxin B Lethality","alternate_titles":[],"description":"Bacterial superantigens are virulence factors that cause toxic shock syndrome. 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Relevance triaged manually: a multi-tissue time course of lethal superantigen challenge, matching the multi-organ dysfunction node."],"contexts":[{"id":"disorder:Toxic_Shock_Syndrome","name":"Toxic Shock Syndrome","kind":"Disorder","source_path":"kb/disorders/Toxic_Shock_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Toxic_Shock_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Toxic_Shock_Syndrome.html#dataset-geo-gse52474"}],"context_names":["Toxic Shock Syndrome"],"disease_names":["Toxic Shock Syndrome"],"disease_name":"Toxic Shock Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Toxic_Shock_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Toxic_Shock_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Toxic_Shock_Syndrome.html#dataset-geo-gse52474"]},{"id":"dataset:geo:gse52641","accession":"geo:GSE52641","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE52641","title":"Genomic profiling of chromophobe renal cell carcinoma by array-based comparative genomic hybridization","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[4],"sample_count":4,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["GEO series matched because chromophobe renal cell carcinoma is named in the dataset's own title. Array CGH copy-number profiling, the method class that established the chromosome-loss signature. Small series (n=4). Relevance confirmed manually; retrieved 2026-08-15."],"contexts":[{"id":"disorder:Chromophobe_Renal_Cell_Carcinoma","name":"Chromophobe Renal Cell Carcinoma","kind":"Disorder","source_path":"kb/disorders/Chromophobe_Renal_Cell_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chromophobe_Renal_Cell_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chromophobe_Renal_Cell_Carcinoma.html#dataset-geo-gse52641"}],"context_names":["Chromophobe Renal Cell Carcinoma"],"disease_names":["Chromophobe Renal Cell Carcinoma"],"disease_name":"Chromophobe Renal Cell Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association 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Transcriptomic and Physiological Changes Associated with Mammalian Host-Adaptation by Leptospira interrogans Serovar Copenhageni","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"To obtain a more faithful representation of how leptospires respond to host-derived signals, we used RNA-Seq to compare the transcriptome of L. interrogans cultivated within dialysis membrane chambers (DMCs) implanted into the peritoneal cavities of rats with that of organisms grown in vitro.","explanation":"Supports this dataset as a key resource for host-adaptation pathophysiology."}],"notes":[],"contexts":[{"id":"disorder:Leptospirosis","name":"Leptospirosis","kind":"Disorder","source_path":"kb/disorders/Leptospirosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Leptospirosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Leptospirosis.html#dataset-geo-gse53818"}],"context_names":["Leptospirosis"],"disease_names":["Leptospirosis"],"disease_name":"Leptospirosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Leptospirosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Leptospirosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Leptospirosis.html#dataset-geo-gse53818"]},{"id":"dataset:geo:gse55148","accession":"geo:GSE55148","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE55148","title":"Mildly compromised tetrahydrobiopterin biosynthesis mouse mutants exhibit abnormal body fat distribution and abdominal obesity","alternate_titles":[],"description":"Mouse expression profiling study of reduced BH4 biosynthesis (Pts mutant models), relevant to BH4-deficient hyperphenylalaninemia mechanisms.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"Mus musculus","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[{"id":"UBERON:0000955","label":"brain","display_label":"brain tissue","url":"http://purl.obolibrary.org/obo/UBERON_0000955"},{"id":"UBERON:0002107","label":"liver","display_label":"liver tissue","url":"http://purl.obolibrary.org/obo/UBERON_0002107"}],"sample_type_labels":["brain","liver"],"sample_counts":[16],"sample_count":16,"conditions":["Pts mutant mice","wild-type controls"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[{"statement":"BH4-biosynthesis impairment in this model produced metabolic phenotypes relevant to BH4-associated hyperphenylalaninemia.","evidence":[{"reference":"geo:GSE55148","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE55148","reference_title":"Mildly compromised tetrahydrobiopterin biosynthesis mouse mutants exhibit abnormal body fat distribution and abdominal obesity","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"BH4 deficiency due to an autosomal recessive defect in its biosynthetic enzyme 6-pyruvoyltetrahydropterin synthase (PTPS, encoded by the PTS gene) leads to a variant form of hyperphenylalaninemia concomitant with severe deficiency of brain monoamine neurotransmitters.","explanation":"Summary supports translational relevance of BH4-pathway models to differential hyperphenylalaninemia biology."}]}],"findings_text":["BH4-biosynthesis impairment in this model produced metabolic phenotypes relevant to BH4-associated hyperphenylalaninemia."],"evidence":[{"reference":"geo:GSE55148","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE55148","reference_title":"Mildly compromised tetrahydrobiopterin biosynthesis mouse mutants exhibit abnormal body fat distribution and abdominal obesity","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"BH4 deficiency due to an autosomal recessive defect in its biosynthetic enzyme 6-pyruvoyltetrahydropterin synthase (PTPS, encoded by the PTS gene) leads to a variant form of hyperphenylalaninemia concomitant with severe deficiency of brain monoamine neurotransmitters.","explanation":"Dataset-level summary supports relevance to BH4-associated hyperphenylalaninemia mechanisms."}],"notes":[],"contexts":[{"id":"disorder:Phenylketonuria","name":"Phenylketonuria","kind":"Disorder","source_path":"kb/disorders/Phenylketonuria.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Phenylketonuria.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Phenylketonuria.html#dataset-geo-gse55148"}],"context_names":["Phenylketonuria"],"disease_names":["Phenylketonuria"],"disease_name":"Phenylketonuria","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Phenylketonuria.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Phenylketonuria.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Phenylketonuria.html#dataset-geo-gse55148"]},{"id":"dataset:geo:gse55594","accession":"geo:GSE55594","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE55594","title":"Gene expression profiling of breast fibroadenomas","alternate_titles":[],"description":"Fibroadenomas are the most common benign breast tumors in women under 30. Unlike their malignant counterparts, relatively molecular profiling has been done on fibroadenomas. Here we performed gene expression profiling on ten fibroadenomas in order to better characterize these tumors. Through targeted amplicon sequencing, we have found that six of these tumors have MED12 mutations. We show that the MED12 mutations, among others, are associated with activated estrogen signaling, as well as increased invasiveness through upregulation of ECM remodelling genes.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[10],"sample_count":10,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:25038752"],"publication_contexts":[{"context_id":"disorder:Breast_Fibroadenoma","publication":"PMID:25038752"}],"publication":"PMID:25038752","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/25038752","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Breast Fibroadenoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Breast_Fibroadenoma","name":"Breast Fibroadenoma","kind":"Disorder","source_path":"kb/disorders/Breast_Fibroadenoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Breast_Fibroadenoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Breast_Fibroadenoma.html#dataset-geo-gse55594"}],"context_names":["Breast Fibroadenoma"],"disease_names":["Breast Fibroadenoma"],"disease_name":"Breast Fibroadenoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Breast_Fibroadenoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Breast_Fibroadenoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Breast_Fibroadenoma.html#dataset-geo-gse55594"]},{"id":"dataset:geo:gse56158","accession":"geo:GSE56158","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE56158","title":"Transcriptomic analysis of human cybrid cell lines harboring increasing levels of the mitochondrial DNA (mtDNA) 3243A>G mutation","alternate_titles":[],"description":"RNA-seq of isogenic somatic-cell cybrids spanning the complete range of m.3243A>G heteroplasmy, with paired cellular phenotyping, designed to test how continuous variation in mutant load maps onto discrete clinical syndromes.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[8],"sample_count":8,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:25192935"],"publication_contexts":[{"context_id":"disorder:MELAS_Syndrome","publication":"PMID:25192935"}],"publication":"PMID:25192935","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/25192935","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:25192935","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/25192935","reference_title":"Progressive increase in mtDNA 3243A>G heteroplasmy causes abrupt transcriptional reprogramming.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Small increases in mutant mtDNAs caused relatively modest defects in oxidative capacity but resulted in sharp transitions in cellular phenotype and gene expression.","explanation":"Demonstrates threshold-like transcriptional switching rather than a graded response, which is the shape a mechanism must have to turn continuous heteroplasmy into discrete syndromes."},{"reference":"PMID:25192935","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/25192935","reference_title":"Progressive increase in mtDNA 3243A>G heteroplasmy causes abrupt transcriptional reprogramming.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"a major factor in the phenotypic variation in heteroplasmic mtDNA mutations is the limited number of states that the nucleus can acquire in response to progressive changes in mitochondrial retrograde signaling","explanation":"States the proposed explanation for genotype-phenotype discordance that this dataset was generated to test."}],"notes":["Addresses the genotype-phenotype gap from the opposite direction to the retina data: one nuclear background, heteroplasmy varied experimentally. Its result - that the nucleus has only a few discrete states available - is a mechanistic proposal for why a continuous variable produces named syndromes. Cybrids are an immortalized non-neural cell line, so the thresholds are not directly transferable to patient tissue."],"contexts":[{"id":"disorder:MELAS_Syndrome","name":"MELAS Syndrome","kind":"Disorder","source_path":"kb/disorders/MELAS_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MELAS_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/MELAS_Syndrome.html#dataset-geo-gse56158"}],"context_names":["MELAS Syndrome"],"disease_names":["MELAS Syndrome"],"disease_name":"MELAS Syndrome","same_context_model_ids":["model:kb/disorders/MELAS_Syndrome.yaml:m.3243A>G patient iPSC-derived neurons"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/MELAS_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MELAS_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/MELAS_Syndrome.html#dataset-geo-gse56158"]},{"id":"dataset:geo:gse56192","accession":"geo:GSE56192","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE56192","title":"Transcriptomic analysis of the Novel Middle East Respiratory Syndrome Coronavirus (Human, MRC5 cells)","alternate_titles":[],"description":"We will use the EMC/2012 strain of the novel beta Coronavirus called Middle East Respiratory Syndrome Coronavirus (MERS-CoV). It was initially passaged on Vero E6 cells in Saudi Arabia before being sequenced at the Erasmus Medical College in Rotterdam, Netherlands by Dr Ron Fouchier. We propose to perform a time course of infection of hCoV-EMC on MRC5 cells (Human Lung origin) and Vero cells (African Green Monkey Kidney cells). Both cell lines readily grow and replicate the virus.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[37],"sample_count":37,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Middle East Respiratory Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Middle_East_Respiratory_Syndrome","name":"Middle East Respiratory Syndrome","kind":"Disorder","source_path":"kb/disorders/Middle_East_Respiratory_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Middle_East_Respiratory_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Middle_East_Respiratory_Syndrome.html#dataset-geo-gse56192"}],"context_names":["Middle East Respiratory Syndrome"],"disease_names":["Middle East Respiratory Syndrome"],"disease_name":"Middle East Respiratory Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Middle_East_Respiratory_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Middle_East_Respiratory_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Middle_East_Respiratory_Syndrome.html#dataset-geo-gse56192"]},{"id":"dataset:geo:gse56284","accession":"geo:GSE56284","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE56284","title":"Transcriptome profiling of severe spinal muscular atrophy mouse embryonic stem cell-derived motor neurons","alternate_titles":[],"description":"RNA-seq profiling of mouse embryonic stem cell-derived motor neurons from SMA model and control lines.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[{"id":"CL:0000100","label":"motor neuron","display_label":"motor neuron","url":"http://purl.obolibrary.org/obo/CL_0000100"}],"sample_type_labels":["motor neuron"],"sample_counts":[6],"sample_count":6,"conditions":["SMA mouse model","control"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["D7 Hb9:GFP mESC-derived motor neurons from SMA and control lines."],"contexts":[{"id":"disorder:Spinal_Muscular_Atrophy","name":"Spinal Muscular Atrophy","kind":"Disorder","source_path":"kb/disorders/Spinal_Muscular_Atrophy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Spinal_Muscular_Atrophy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Spinal_Muscular_Atrophy.html#dataset-geo-gse56284"}],"context_names":["Spinal Muscular Atrophy"],"disease_names":["Spinal Muscular Atrophy"],"disease_name":"Spinal Muscular Atrophy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Spinal_Muscular_Atrophy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Spinal_Muscular_Atrophy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Spinal_Muscular_Atrophy.html#dataset-geo-gse56284"]},{"id":"dataset:geo:gse56402","accession":"geo:GSE56402","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE56402","title":"A recessive point mutation is responsible for pleiotropic effects in a scube3 mutant mouse","alternate_titles":[],"description":"Expression profiling from the Munich ENU kta41 line, the Scube3 N294K mouse curated above as an animal model. It is a mouse dataset carrying a mouse ENU allele, so it reports the model rather than the patients.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"house mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:27815347"],"publication_contexts":[{"context_id":"disorder:SCUBE3-Related_Short_Stature_Syndrome","publication":"PMID:27815347"}],"publication":"PMID:27815347","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/27815347","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE56402","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE56402","reference_title":"A recessive point mutation is responsible for pleiotropic effects in a scube3 mutant mouse","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"Whole genome sequencing approaches revealed a C to A transversion on position 882 in Scube3 that leads to a missense mutation in the protein (Asn294Lys).","explanation":"The repository record identifies the allele profiled as Scube3 N294K, which is what establishes the dataset's relevance to this entry."}],"notes":["Surfaced by `just discover-datasets` as a GENE_ONLY match and kept after relevance triage: it profiles the Scube3 N294K mutant mouse, curated above as an animal model of this disorder, rather than merely mentioning the gene. N294K is a mouse ENU allele and not a patient variant, so the relevance runs through the model and not through a genotype match. The two other GENE_ONLY candidates from the same search were dropped - one is a SCUBE3 antibody cancer study and one an osteoporosis study - because neither concerns SCUBE3 loss of function in development."],"contexts":[{"id":"disorder:SCUBE3-Related_Short_Stature_Syndrome","name":"SCUBE3-Related Short Stature Syndrome","kind":"Disorder","source_path":"kb/disorders/SCUBE3-Related_Short_Stature_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/SCUBE3-Related_Short_Stature_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/SCUBE3-Related_Short_Stature_Syndrome.html#dataset-geo-gse56402"}],"context_names":["SCUBE3-Related Short Stature Syndrome"],"disease_names":["SCUBE3-Related Short Stature Syndrome"],"disease_name":"SCUBE3-Related Short Stature Syndrome","same_context_model_ids":["model:kb/disorders/SCUBE3-Related_Short_Stature_Syndrome.yaml:Human dental pulp stem cell and pulp-dentin organoid odontoblast model","model:kb/disorders/SCUBE3-Related_Short_Stature_Syndrome.yaml:SCUBE3 loss- and gain-of-function in human bone marrow mesenchymal stem cells"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/SCUBE3-Related_Short_Stature_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/SCUBE3-Related_Short_Stature_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/SCUBE3-Related_Short_Stature_Syndrome.html#dataset-geo-gse56402"]},{"id":"dataset:geo:gse57550","accession":"geo:GSE57550","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE57550","title":"miRNA expression profile in HOS cells exposed to sodium fluoride","alternate_titles":[],"description":"Small non-coding RNA profiling in the same cell system, aimed at the epigenetic arm of fluorosis pathogenesis. The companion resource to the entry's microRNA and histone nodes.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE57550","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE57550","reference_title":"miRNA expression profile in HOS cells exposed to sodium fluoride","supports":"SUPPORT","evidence_source":"OTHER","snippet":"Aberrant change in RUNX2-mediated signaling cascade is one of the decisive steps during the pathogenesis of fluorosis.","explanation":"The stated purpose - epigenetic alterations in fluorosis - and the RUNX2 framing. Graded OTHER as a repository record."}],"notes":[],"contexts":[{"id":"disorder:Skeletal_Fluorosis","name":"Skeletal Fluorosis","kind":"Disorder","source_path":"kb/disorders/Skeletal_Fluorosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Skeletal_Fluorosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Skeletal_Fluorosis.html#dataset-geo-gse57550"}],"context_names":["Skeletal Fluorosis"],"disease_names":["Skeletal Fluorosis"],"disease_name":"Skeletal Fluorosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Skeletal_Fluorosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Skeletal_Fluorosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Skeletal_Fluorosis.html#dataset-geo-gse57550"]},{"id":"dataset:geo:gse5781","accession":"geo:GSE5781","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE5781","title":"Array CGH in TAR syndrome","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[4],"sample_count":4,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:9905","label":"RBM8A","display_label":"RBM8A","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/9905"}],"genes":["RBM8A"],"platforms":[],"platform":null,"publications":["PMID:17236129"],"publication_contexts":[{"context_id":"disorder:Thrombocytopenia-Absent_Radius_Syndrome","publication":"PMID:17236129"}],"publication":"PMID:17236129","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/17236129","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["The array CGH series deposited by the study that identified the recurrent 200-kb 1q21.1 microdeletion, and therefore the primary data behind the null allele modelled in this entry. 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Useful as a broader transcriptomic reference set for tumor-versus-normal contrasts and for anchoring subtype-level or pathway-level signatures in a larger patient cohort.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0001264","label":"pancreas","display_label":"pancreas","url":"http://purl.obolibrary.org/obo/UBERON_0001264"}],"sample_type_labels":["pancreas"],"sample_counts":[130],"sample_count":130,"conditions":["pancreatic ductal adenocarcinoma tumor tissue","adjacent non-tumor pancreatic tissue"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:27197190"],"publication_contexts":[{"context_id":"disorder:Pancreatic_Ductal_Adenocarcinoma","publication":"PMID:27197190"}],"publication":"PMID:27197190","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/27197190","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["GEO reports 69 pancreatic tumors and 61 adjacent non-tumor tissues, with earlier Affymetrix data from GSE28735 incorporated into the merged normalized cohort. Useful as a bulk-expression complement to the single-cell and spatial resources above."],"contexts":[{"id":"disorder:Pancreatic_Ductal_Adenocarcinoma","name":"Pancreatic Ductal Adenocarcinoma","kind":"Disorder","source_path":"kb/disorders/Pancreatic_Ductal_Adenocarcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pancreatic_Ductal_Adenocarcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pancreatic_Ductal_Adenocarcinoma.html#dataset-geo-gse62452"}],"context_names":["Pancreatic Ductal Adenocarcinoma"],"disease_names":["Pancreatic Ductal Adenocarcinoma"],"disease_name":"Pancreatic Ductal Adenocarcinoma","same_context_model_ids":["model:kb/disorders/Pancreatic_Ductal_Adenocarcinoma.yaml:Human PDAC Cell and Organoid RAS-Response Models"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Pancreatic_Ductal_Adenocarcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pancreatic_Ductal_Adenocarcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Pancreatic_Ductal_Adenocarcinoma.html#dataset-geo-gse62452"]},{"id":"dataset:geo:gse62584","accession":"geo:GSE62584","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE62584","title":"PBMC gene expression of early onset of the first demyelinating event of acute optic neuritis","alternate_titles":[],"description":"Optic neuritis (ON) is a common manifestation of multiple sclerosis (MS); it appears as the presenting symptom in about 25% of MS patients and occurs in 30–70% of patients with MS during the course of their illness Purpose. To evaluate the molecular pathways that operate in the early phase of acute ON by studying gene expression profiles of peripheral blood mononuclear cells (PBMCs) subpopulations including CD19+ B cells, CD14+ macrophages, CD4+ and CD8+ T cells.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[60],"sample_count":60,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:25593026"],"publication_contexts":[{"context_id":"disorder:Optic_Neuritis","publication":"PMID:25593026"}],"publication":"PMID:25593026","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/25593026","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Optic Neuritis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Optic_Neuritis","name":"Optic Neuritis","kind":"Disorder","source_path":"kb/disorders/Optic_Neuritis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Optic_Neuritis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Optic_Neuritis.html#dataset-geo-gse62584"}],"context_names":["Optic Neuritis"],"disease_names":["Optic Neuritis"],"disease_name":"Optic Neuritis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Optic_Neuritis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Optic_Neuritis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Optic_Neuritis.html#dataset-geo-gse62584"]},{"id":"dataset:geo:gse63142","accession":"geo:GSE63142","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE63142","title":"Asthma II","alternate_titles":[],"description":"Bronchial epithelial cells from normal controls, mild-moderate, and severe asthmatic patients to identify severity-associated gene expression.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"CL:0002328","label":"bronchial epithelial cell","display_label":"bronchial epithelial cell","url":"http://purl.obolibrary.org/obo/CL_0002328"}],"sample_type_labels":["bronchial epithelial cell"],"sample_counts":[155],"sample_count":155,"conditions":["severe asthma (n=56)","mild-moderate asthma (n=72)","healthy controls (n=27)"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["Agilent Whole Human Genome Microarray 4x44K"],"platform":"Agilent Whole Human Genome Microarray 4x44K","publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":[],"contexts":[{"id":"disorder:Asthma","name":"Asthma","kind":"Disorder","source_path":"kb/disorders/Asthma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Asthma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Asthma.html#dataset-geo-gse63142"}],"context_names":["Asthma"],"disease_names":["Asthma"],"disease_name":"Asthma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Asthma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Asthma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Asthma.html#dataset-geo-gse63142"]},{"id":"dataset:geo:gse63908","accession":"geo:GSE63908","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE63908","title":"Microarray analysis of Wild-type vs. Brpf1-deficient E8.75 mouse embryo","alternate_titles":[],"description":"Two-color microarray comparison of three pairs of control and Brpf1-deficient E8.75 mouse embryos.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"Mus musculus","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[3],"sample_count":3,"conditions":["Wild-type E8.75 mouse embryo","Brpf1-deficient E8.75 mouse embryo"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (GPL13912)"],"platform":"Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (GPL13912)","publications":["PMID:25773539"],"publication_contexts":[{"context_id":"disorder:BRPF1-Related_Intellectual_Disability","publication":"PMID:25773539"}],"publication":"PMID:25773539","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/25773539","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["GEO lists three array samples, each hybridizing labeled material from a control-mutant pair: three samples represent six embryos, not three total embryos. Whole-embryo composition and global null genotype limit inference about human heterozygous neural cells."],"contexts":[{"id":"disorder:BRPF1-Related_Intellectual_Disability","name":"BRPF1-Related Intellectual Disability","kind":"Disorder","source_path":"kb/disorders/BRPF1-Related_Intellectual_Disability.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/BRPF1-Related_Intellectual_Disability.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/BRPF1-Related_Intellectual_Disability.html#dataset-geo-gse63908"}],"context_names":["BRPF1-Related Intellectual Disability"],"disease_names":["BRPF1-Related Intellectual Disability"],"disease_name":"BRPF1-Related Intellectual Disability","same_context_model_ids":["model:kb/disorders/BRPF1-Related_Intellectual_Disability.yaml:BRPF1 Pro370Ser patient-derived lymphoblastoid cells","model:kb/disorders/BRPF1-Related_Intellectual_Disability.yaml:Brpf1-knockdown mouse hippocampal neuron cultures","model:kb/disorders/BRPF1-Related_Intellectual_Disability.yaml:Brpf1-knockdown mouse MGE-derived interneuron cultures","model:kb/disorders/BRPF1-Related_Intellectual_Disability.yaml:Brpf1-null fetal-liver and neonatal marrow colony cultures","model:kb/disorders/BRPF1-Related_Intellectual_Disability.yaml:BRPF1-null human H1 embryonic stem cells with inducible rescue","model:kb/disorders/BRPF1-Related_Intellectual_Disability.yaml:Emx1-lineage Brpf1 conditional cortical neuron cultures","model:kb/disorders/BRPF1-Related_Intellectual_Disability.yaml:Inducible Brpf1-null mouse embryonic fibroblasts"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/BRPF1-Related_Intellectual_Disability.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/BRPF1-Related_Intellectual_Disability.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/BRPF1-Related_Intellectual_Disability.html#dataset-geo-gse63908"]},{"id":"dataset:geo:gse63949","accession":"geo:GSE63949","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE63949","title":"Detection of copy number variation in patients with Pelizaeus-Merzbacher disease (PMD) - NimbleGen","alternate_titles":[],"description":"The objective of the study was to investigate the extent of duplicated, triplicated, and quadruplicated regions in PMD patients so that junction analysis could be performed.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[10],"sample_count":10,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:25749076"],"publication_contexts":[{"context_id":"disorder:Pelizaeus_Merzbacher_Disease","publication":"PMID:25749076"}],"publication":"PMID:25749076","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/25749076","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Pelizaeus-Merzbacher Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Pelizaeus_Merzbacher_Disease","name":"Pelizaeus-Merzbacher Disease","kind":"Disorder","source_path":"kb/disorders/Pelizaeus_Merzbacher_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pelizaeus_Merzbacher_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pelizaeus-Merzbacher_Disease.html#dataset-geo-gse63949"}],"context_names":["Pelizaeus-Merzbacher Disease"],"disease_names":["Pelizaeus-Merzbacher Disease"],"disease_name":"Pelizaeus-Merzbacher Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association 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is a direct human-cell transcriptomic resource for Costello syndrome astroglial pathology."}],"notes":[],"contexts":[{"id":"disorder:Costello_Syndrome","name":"Costello Syndrome","kind":"Disorder","source_path":"kb/disorders/Costello_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Costello_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Costello_Syndrome.html#dataset-geo-gse64194"}],"context_names":["Costello Syndrome"],"disease_names":["Costello Syndrome"],"disease_name":"Costello Syndrome","same_context_model_ids":["model:kb/disorders/Costello_Syndrome.yaml:Costello syndrome atrial-like cardiomyocyte model","model:kb/disorders/Costello_Syndrome.yaml:Costello syndrome patient fibroblast models"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a 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Certain recurrent genetic abnormalities characteristics of different genetic subtypes have been described. Hyperdiploid myeloma characterized by recurrent trisomies is the most common genetic subtypes. However little is know about it's biology. Another common genetic abnormality is chromosome 13 deletion which is also associated with inferior prognosis. This abnormality is already present at the pre-malignant MGUS stage and is clonally selected with disease progression. Although it is biologically and clinically important the molecular consequence of chromosome 13 deletion is unknown.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[162],"sample_count":162,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:17409404"],"publication_contexts":[{"context_id":"disorder:Plasma_Cell_Neoplasm","publication":"PMID:17409404"}],"publication":"PMID:17409404","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/17409404","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Plasma Cell Neoplasm (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Plasma_Cell_Neoplasm","name":"Plasma Cell Neoplasm","kind":"Disorder","source_path":"kb/disorders/Plasma_Cell_Neoplasm.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Plasma_Cell_Neoplasm.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Plasma_Cell_Neoplasm.html#dataset-geo-gse6477"}],"context_names":["Plasma Cell Neoplasm"],"disease_names":["Plasma Cell Neoplasm"],"disease_name":"Plasma Cell Neoplasm","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Plasma_Cell_Neoplasm.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Plasma_Cell_Neoplasm.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Plasma_Cell_Neoplasm.html#dataset-geo-gse6477"]},{"id":"dataset:geo:gse64823","accession":"geo:GSE64823","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE64823","title":"Gene expression data of cultured primary microglia from neonatal control and Cstb-/- mice.","alternate_titles":[],"description":"Cystain B (Cstb) is a ubiquitously expressed cysteine protease inhibitor and mutations of the CSTB gene lead to the neurodegenerative disease progressive myoclonus epilepsy of Unverricht-Lundorg type (EPM1). We are interested in the microglia-specific, Cstb-dependent gene-expression changes in mice and in this data set, we include gene-level expression data from cultured primary microglia of control and Cstb-/- mice extracted from neonatal mice at P5 and we identified 156 differentially-expressed genes in Cstb-/- microglia.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[8],"sample_count":8,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:27355630"],"publication_contexts":[{"context_id":"disorder:Progressive_Myoclonus_Epilepsy","publication":"PMID:27355630"}],"publication":"PMID:27355630","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/27355630","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Progressive Myoclonus Epilepsy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Progressive_Myoclonus_Epilepsy","name":"Progressive Myoclonus Epilepsy","kind":"Disorder","source_path":"kb/disorders/Progressive_Myoclonus_Epilepsy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Progressive_Myoclonus_Epilepsy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Progressive_Myoclonus_Epilepsy.html#dataset-geo-gse64823"}],"context_names":["Progressive Myoclonus Epilepsy"],"disease_names":["Progressive Myoclonus Epilepsy"],"disease_name":"Progressive Myoclonus Epilepsy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Progressive_Myoclonus_Epilepsy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Progressive_Myoclonus_Epilepsy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Progressive_Myoclonus_Epilepsy.html#dataset-geo-gse64823"]},{"id":"dataset:geo:gse65123","accession":"geo:GSE65123","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE65123","title":"Gene expression analysis during acute hepatitis C virus infection associates dendritic cell activation with viral clearance","alternate_titles":[],"description":"Background and Aims: Viral clearance during acute hepatitis C virus (HCV) infection is associated with the induction of potent antiviral T-cell responses. Since dendritic cells (DC) are essential in the activation of primary T-cell responses our goal was to analyze gene expression in DC from patients during acute HCV infection. Methods: By using microarrays, gene expression was compared in resting and activated peripheral blood plasmacytoid (pDC) and myeloid (mDC) DC from acute HCV resolving patients (AR) and from those who become chronically infected (ANR), as well as in HCV chronically infected patients (CHR) and healthy seronegative individuals (CTRL).","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[56],"sample_count":56,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:26447929"],"publication_contexts":[{"context_id":"disorder:Hepatitis_C","publication":"PMID:26447929"}],"publication":"PMID:26447929","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/26447929","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Acute Hepatitis C Virus Infection (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Hepatitis_C","name":"Hepatitis C","kind":"Disorder","source_path":"kb/disorders/Hepatitis_C.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatitis_C.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hepatitis_C.html#dataset-geo-gse65123"}],"context_names":["Hepatitis C"],"disease_names":["Hepatitis C"],"disease_name":"Hepatitis C","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hepatitis_C.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatitis_C.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hepatitis_C.html#dataset-geo-gse65123"]},{"id":"dataset:geo:gse65399","accession":"geo:GSE65399","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE65399","title":"Epigenetic therapy for Friedreich ataxia.","alternate_titles":[],"description":"Expression profiling of an FRDA neuronal cell model treated with the histone deacetylase inhibitor 109/RG2833, the in vitro arm of the epigenetic reactivation study that accompanied a phase I patient trial.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[75],"sample_count":75,"conditions":["FRDA neuronal cell model, HDAC inhibitor treated","FRDA neuronal cell model, untreated"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:25159818"],"publication_contexts":[{"context_id":"disorder:Friedreich_Ataxia","publication":"PMID:25159818"}],"publication":"PMID:25159818","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/25159818","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE65399","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE65399","reference_title":"Epigenetic therapy for Friedreich ataxia.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"In the neuronal cell model, HDACi 109/RG2833 increases FXN mRNA levels and frataxin protein, with concomitant changes in the epigenetic state of the gene.","explanation":"The GEO summary describes the HDAC-inhibitor reactivation experiment profiled by this series."}],"notes":[],"contexts":[{"id":"disorder:Friedreich_Ataxia","name":"Friedreich Ataxia","kind":"Disorder","source_path":"kb/disorders/Friedreich_Ataxia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Friedreich_Ataxia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Friedreich_Ataxia.html#dataset-geo-gse65399"}],"context_names":["Friedreich Ataxia"],"disease_names":["Friedreich Ataxia"],"disease_name":"Friedreich Ataxia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Friedreich_Ataxia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Friedreich_Ataxia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Friedreich_Ataxia.html#dataset-geo-gse65399"]},{"id":"dataset:geo:gse65914","accession":"geo:GSE65914","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE65914","title":"Th1/Th17 Immune Response in Rosacea","alternate_titles":[],"description":"Human facial biopsy transcriptomic dataset spanning rosacea subtypes and healthy controls, used to define adaptive immune and inflammatory cell programs across erythematotelangiectatic, papulopustular, and phymatous disease.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[58],"sample_count":58,"conditions":["erythematotelangiectatic rosacea","papulopustular rosacea","phymatous rosacea","healthy control facial skin"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:25848978"],"publication_contexts":[{"context_id":"disorder:Rosacea","publication":"PMID:25848978"}],"publication":"PMID:25848978","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/25848978","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE65914","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE65914","reference_title":"Th1/Th17 Immune Response in Rosacea","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"The T cell response is dominated by Th1/Th17-polarized immune cells, as demonstrated by significant upregulation of IFNγ or IL-17, for example.","explanation":"This GEO series directly supports subtype-spanning adaptive immune polarization in human rosacea tissue."}],"notes":[],"contexts":[{"id":"disorder:Rosacea","name":"Rosacea","kind":"Disorder","source_path":"kb/disorders/Rosacea.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rosacea.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Rosacea.html#dataset-geo-gse65914"}],"context_names":["Rosacea"],"disease_names":["Rosacea"],"disease_name":"Rosacea","same_context_model_ids":["model:kb/disorders/Rosacea.yaml:HaCaT keratinocytes under simulated rosacea conditions","model:kb/disorders/Rosacea.yaml:Paired lesional and non-lesional papulopustular rosacea skin explants","model:kb/disorders/Rosacea.yaml:SZ95 sebocyte and live Demodex mite co-culture"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Rosacea.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rosacea.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Rosacea.html#dataset-geo-gse65914"]},{"id":"dataset:geo:gse66273","accession":"geo:GSE66273","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE66273","title":"Genome-wide analysis of placental gene expression in severe preterm preeclampsia","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[17],"sample_count":17,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:30135684"],"publication_contexts":[{"context_id":"disorder:HELLP_Syndrome","publication":"PMID:30135684"}],"publication":"PMID:30135684","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/30135684","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Selected as a DIRECT candidate by `just discover-datasets HELLP_Syndrome` and manually triaged: the GEO series summary states the placentas came from women with preterm severe preeclampsia \"with or without HELLP syndrome\", so HELLP cases are genuinely represented rather than the accession merely matching on a disease name. The GENE_ONLY candidates returned by the same search (HADHA-matched cardiomyocyte and murine Treg series) were rejected as Named Entity Confusion - they match the gene symbol cited on this entry's fetal fatty-acid-oxidation arm and have nothing to do with HELLP. Carries no evidence block, per the dataset-curation convention: the accession is verified to exist and be relevant, which is not the same as having an exact quotable finding about HELLP."],"contexts":[{"id":"disorder:HELLP_Syndrome","name":"HELLP Syndrome","kind":"Disorder","source_path":"kb/disorders/HELLP_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/HELLP_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/HELLP_Syndrome.html#dataset-geo-gse66273"}],"context_names":["HELLP Syndrome"],"disease_names":["HELLP Syndrome"],"disease_name":"HELLP Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/HELLP_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/HELLP_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/HELLP_Syndrome.html#dataset-geo-gse66273"]},{"id":"dataset:geo:gse66476","accession":"geo:GSE66476","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE66476","title":"Interferon-γ response against C. burnetii of peripheral blood mononuclear cells in the development of chronic Q fever","alternate_titles":[],"description":"Background: Q fever is caused by the Coxiella burnetii, an intracellular bacterium that infects mononuclear cells. In some individuals, it causes a persistent cardiovascular infection (chronic Q fever). The aim of present study was to investigate the C. burnetii-induced IFN-γ response in chronic Q fever patients. Methods: IFN-γ was measured in supernatants of C. burnetii-stimulated peripheral blood mononuclear cells (PBMCs) of patients. Gene-expression profiles of the IFN-γ pathway in PBMCs after incubation with C. burnetii were compared between chronic Q fever patients and control individuals. Results: IFN-γ production by PBMCs of chronic Q fever patients incubated with C.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[30],"sample_count":30,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Q Fever (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Q_Fever","name":"Q Fever","kind":"Disorder","source_path":"kb/disorders/Q_Fever.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Q_Fever.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Q_Fever.html#dataset-geo-gse66476"}],"context_names":["Q Fever"],"disease_names":["Q Fever"],"disease_name":"Q Fever","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Q_Fever.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Q_Fever.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Q_Fever.html#dataset-geo-gse66476"]},{"id":"dataset:geo:gse67311","accession":"geo:GSE67311","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE67311","title":"Peripheral Blood Gene Expression in Fibromyalgia Patients Reveals  Potential Biological Markers and Physiological Pathways","alternate_titles":[],"description":"Fibromyalgia (FM) is a common pain disorder characterized by dysregulation in the processing of pain. Although FM has similarities with other rheumatologic pain disorders, the search for objective markers has not been successful. In the current study we analyzed gene expression in the whole blood of 70 fibromyalgia patients and 70 healthy matched controls. Global molecular profiling revealed an upregulation of several inflammatory molecules in FM patients and downregulation of specific pathways related to hypersensitivity and allergy. There was a differential expression of genes in known pathways for pain processing, such as glutamine/glutamate signaling and axonal development.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[142],"sample_count":142,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:27157394"],"publication_contexts":[{"context_id":"disorder:Fibromyalgia","publication":"PMID:27157394"}],"publication":"PMID:27157394","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/27157394","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Fibromyalgia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Fibromyalgia","name":"Fibromyalgia","kind":"Disorder","source_path":"kb/disorders/Fibromyalgia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fibromyalgia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Fibromyalgia.html#dataset-geo-gse67311"}],"context_names":["Fibromyalgia"],"disease_names":["Fibromyalgia"],"disease_name":"Fibromyalgia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Fibromyalgia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fibromyalgia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Fibromyalgia.html#dataset-geo-gse67311"]},{"id":"dataset:geo:gse67472","accession":"geo:GSE67472","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE67472","title":"Airway epithelial gene expression in asthma versus healthy controls","alternate_titles":[],"description":"Bronchial epithelial brushings from mild-to-moderate asthmatics (not on inhaled steroids) and healthy controls, stratified by Type 2 inflammation markers (POSTN, SERPINB2, CLCA1).","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"CL:0002328","label":"bronchial epithelial cell","display_label":"bronchial epithelial cell","url":"http://purl.obolibrary.org/obo/CL_0002328"}],"sample_type_labels":["bronchial epithelial cell"],"sample_counts":[105],"sample_count":105,"conditions":["mild-to-moderate asthma (n=62)","healthy controls (n=43)"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["Affymetrix Human Genome U133 Plus 2.0"],"platform":"Affymetrix Human Genome U133 Plus 2.0","publications":["PMID:25611785"],"publication_contexts":[{"context_id":"disorder:Asthma","publication":"PMID:25611785"}],"publication":"PMID:25611785","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/25611785","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identifies Type 2 inflammation gene signature. Useful for studying eosinophilic asthma endotypes."],"contexts":[{"id":"disorder:Asthma","name":"Asthma","kind":"Disorder","source_path":"kb/disorders/Asthma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Asthma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Asthma.html#dataset-geo-gse67472"}],"context_names":["Asthma"],"disease_names":["Asthma"],"disease_name":"Asthma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Asthma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Asthma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Asthma.html#dataset-geo-gse67472"]},{"id":"dataset:geo:gse67784","accession":"geo:GSE67784","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE67784","title":"A Gene Expression-based Blood Diagnostic for Symptomatic Transthyretin Amyloidosis Revealing Male and Female-specific Signatures","alternate_titles":[],"description":"Early diagnosis of transthyretin (TTR) amyloid diseases remains challenging because of variable disease penetrance. Currently, patients must have an amyloid positive tissue biopsy to be eligible for disease modifying therapies. Early diagnosis is often difficult because the patient exhibits apparent symptoms of polyneuropathy or cardiomyopathy, but has a negative amyloid biopsy. Thus, there is a pressing need for more objective, quantitative diagnostics and biomarkers of TTR-aggregation-associated polyneuropathy and cardiomyopathy. This is especially true in the context of clinical trials demonstrating significant disease modifying effects, e.g.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[309],"sample_count":309,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:27570551"],"publication_contexts":[{"context_id":"disorder:ATTR_Amyloidosis","publication":"PMID:27570551"}],"publication":"PMID:27570551","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/27570551","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Hereditary Transthyretin Amyloidosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:ATTR_Amyloidosis","name":"Hereditary Transthyretin Amyloidosis","kind":"Disorder","source_path":"kb/disorders/ATTR_Amyloidosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/ATTR_Amyloidosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hereditary_Transthyretin_Amyloidosis.html#dataset-geo-gse67784"}],"context_names":["Hereditary Transthyretin Amyloidosis"],"disease_names":["Hereditary Transthyretin Amyloidosis"],"disease_name":"Hereditary Transthyretin Amyloidosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/ATTR_Amyloidosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/ATTR_Amyloidosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hereditary_Transthyretin_Amyloidosis.html#dataset-geo-gse67784"]},{"id":"dataset:geo:gse67933","accession":"geo:GSE67933","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE67933","title":"RNA profiling by deepSAGE sequencing in the cortex of a migraine mouse model after induction of cortical spreading depression","alternate_titles":[],"description":"Bulk transcriptomic dataset from mouse cortex after experimentally induced cortical spreading depression, providing a direct molecular resource for aura-relevant brain-state changes.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[{"id":"UBERON:0000955","label":"brain","display_label":"brain cortex","url":"http://purl.obolibrary.org/obo/UBERON_0000955"}],"sample_type_labels":["brain"],"sample_counts":[24],"sample_count":24,"conditions":["cortical spreading depression migraine model","control cortex"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["GEO summary describes deepSAGE cortex profiling after induced cortical spreading depression in a migraine model."],"contexts":[{"id":"disorder:Migraine_with_Aura","name":"Migraine with aura","kind":"Disorder","source_path":"kb/disorders/Migraine_with_Aura.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Migraine_with_Aura.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Migraine_with_aura.html#dataset-geo-gse67933"}],"context_names":["Migraine with aura"],"disease_names":["Migraine with aura"],"disease_name":"Migraine with aura","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Migraine_with_Aura.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Migraine_with_Aura.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Migraine_with_aura.html#dataset-geo-gse67933"]},{"id":"dataset:geo:gse68134","accession":"geo:GSE68134","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE68134","title":"DNA methylation profiles of fibroblasts and induced pluripotent stem cells (iPSCs) from individuals with Zellweger spectrum disorder (ZSD), a class of peroxisome biogenesis disorder, and healthy controls","alternate_titles":[],"description":"Zellweger spectrum disorder (PBD-ZSD) is a disease continuum caused by mutations in a subset of PEX genes required for normal peroxisome assembly and function. Their clinical manifestations highlight the importance of peroxisomes in the development and functions of the central nervous system, liver, and other organs. Although much is known about peroxisome assembly and activities, the underlying bases for the cell-type specificity of disease are not fully elucidated. We reprogrammed skin fibroblasts from PBD-ZSD patients into induced pluripotent stem cells (iPSCs) and report their DNA methylation profiles as well as those of matching healthy controls.","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[41],"sample_count":41,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Peroxisome Biogenesis Disorder (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Peroxisome_Biogenesis_Disorder","name":"Peroxisome Biogenesis Disorder","kind":"Disorder","source_path":"kb/disorders/Peroxisome_Biogenesis_Disorder.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Peroxisome_Biogenesis_Disorder.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Peroxisome_Biogenesis_Disorder.html#dataset-geo-gse68134"}],"context_names":["Peroxisome Biogenesis Disorder"],"disease_names":["Peroxisome Biogenesis Disorder"],"disease_name":"Peroxisome Biogenesis Disorder","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Peroxisome_Biogenesis_Disorder.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Peroxisome_Biogenesis_Disorder.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Peroxisome_Biogenesis_Disorder.html#dataset-geo-gse68134"]},{"id":"dataset:geo:gse69170","accession":"geo:GSE69170","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE69170","title":"1,25-Dihydroxyvitamin D3 Controls a Cohort of Vitamin D Receptor Target Genes in the Proximal Intestine That Is Enriched for Calcium Regulating Components (RNA-seq)","alternate_titles":[],"description":"Bulk RNA-seq of duodenum from Cyp27b1-null male mice on a vitamin-D-deficient normal-mineral diet or a high-calcium/high-phosphate rescue diet, sampled six hours after vehicle or calcitriol treatment. The four-condition design directly interrogates the intestinal calcitriol-response program downstream of the modeled synthesis defect; it is not a human VDDR1A cohort.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[24],"sample_count":24,"conditions":["Vitamin-D-deficient normal-mineral diet plus vehicle","Vitamin-D-deficient normal-mineral diet plus calcitriol","Vitamin-D-deficient high-calcium/high-phosphate rescue diet plus vehicle","Vitamin-D-deficient high-calcium/high-phosphate rescue diet plus calcitriol"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["GPL13112"],"platform":"GPL13112","publications":["PMID:26041780"],"publication_contexts":[{"context_id":"disorder:Vitamin_D-Dependent_Rickets_Type_1A","publication":"PMID:26041780"}],"publication":"PMID:26041780","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/26041780","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE69170","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE69170","reference_title":"1,25-Dihydroxyvitamin D3 Controls a Cohort of Vitamin D Receptor Target Genes in the Proximal Intestine That Is Enriched for Calcium Regulating Components (RNA-seq)","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"To examine this issue, Cyp27b1 null mice on either a normal or a high calcium/phosphate-containing rescue diet were treated with either vehicle or 1,25(OH)2D3 and evaluated 6h later. RNA samples from duodena were then subjected to RNA-seq analysis and the data analyzed bioinformatically.","explanation":"The accession record directly establishes the genotype, dietary and calcitriol perturbations, intestinal tissue, timing, and RNA-seq assay."}],"notes":["Accession, organism, 24-sample four-group design, platform, and linked publication were verified against the full NCBI GEO record on 2026-08-24. GEO lists this series within SuperSeries GSE69180. Relevance is confined to the Cyp27b1-null mouse and downstream intestinal vitamin-D response."],"contexts":[{"id":"disorder:Vitamin_D-Dependent_Rickets_Type_1A","name":"Vitamin D-Dependent Rickets Type 1A","kind":"Disorder","source_path":"kb/disorders/Vitamin_D-Dependent_Rickets_Type_1A.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Vitamin_D-Dependent_Rickets_Type_1A.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Vitamin_D-Dependent_Rickets_Type_1A.html#dataset-geo-gse69170"}],"context_names":["Vitamin D-Dependent Rickets Type 1A"],"disease_names":["Vitamin D-Dependent Rickets Type 1A"],"disease_name":"Vitamin D-Dependent Rickets Type 1A","same_context_model_ids":["model:kb/disorders/Vitamin_D-Dependent_Rickets_Type_1A.yaml:Patient-derived VDDR-1 keratinocyte cultures"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Vitamin_D-Dependent_Rickets_Type_1A.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Vitamin_D-Dependent_Rickets_Type_1A.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Vitamin_D-Dependent_Rickets_Type_1A.html#dataset-geo-gse69170"]},{"id":"dataset:geo:gse69597","accession":"geo:GSE69597","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE69597","title":"Refining brucellosis diagnosis by blood transcriptional profiling.","alternate_titles":[],"description":"Diagnosis of brucellosis remains challenging for several reasons, including lack of culture sensitivity, nonspecific symptomatology, and high prevalence of positive serology in endemic areas. The main objectives of this study were to identify blood biomarkers specific to brucellosis compared to other endemic infections and to monitor changes in blood biomarkers during treatment. To obtain a global profile of the disease, we employed RNA sequencing (RNAseq) of whole blood RNA to measure host response against brucellosis infection in patients from Macedonia and Spain.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[169],"sample_count":169,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Brucellosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Brucellosis","name":"Brucellosis","kind":"Disorder","source_path":"kb/disorders/Brucellosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Brucellosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Brucellosis.html#dataset-geo-gse69597"}],"context_names":["Brucellosis"],"disease_names":["Brucellosis"],"disease_name":"Brucellosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Brucellosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Brucellosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Brucellosis.html#dataset-geo-gse69597"]},{"id":"dataset:geo:gse69837","accession":"geo:GSE69837","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE69837","title":"Inverse relationship between microRNA-155 and -184 expression with increasing conjunctival inflammation during ocular Chlamydia trachomatis infection","alternate_titles":[],"description":"Trachoma, a preventable blinding eye disease, is initiated by ocular infection with Chlamydia trachomatis (Ct). MicroRNA (miR) are post-transcriptional regulators of gene expression and play a major role in health and disease. We have investigated the miR profile during C. trachomatis infection of epithelial cells in vitro and in vivo during follicular trachoma with current C. trachomatis infection. Small RNA sequencing was carried out on human epithelial cells infected in vitro and on samples from five children with follicular trachoma with current Ct infection and five children with no evidence of clinical trachoma or infection.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[28],"sample_count":28,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:26842862"],"publication_contexts":[{"context_id":"disorder:Trachoma","publication":"PMID:26842862"}],"publication":"PMID:26842862","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/26842862","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Trachoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Trachoma","name":"Trachoma","kind":"Disorder","source_path":"kb/disorders/Trachoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Trachoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Trachoma.html#dataset-geo-gse69837"}],"context_names":["Trachoma"],"disease_names":["Trachoma"],"disease_name":"Trachoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Trachoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Trachoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Trachoma.html#dataset-geo-gse69837"]},{"id":"dataset:geo:gse70511","accession":"geo:GSE70511","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE70511","title":"Aggressive gene expression signiture of waldenstrom macroglobulinemia with deletion 6q","alternate_titles":[],"description":"Waldenstom macroglobulinemia (WM) with 6q del is still unknown. In the present study, we analyzed gene expression signiture of WM with 6q del. B-cell receptor signaling pathway, and IL21/IL21-R pathway were up-regulated in WM with 6q del.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[8],"sample_count":8,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:30402490"],"publication_contexts":[{"context_id":"disorder:Waldenstrom_Macroglobulinemia","publication":"PMID:30402490"}],"publication":"PMID:30402490","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/30402490","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Waldenstrom Macroglobulinemia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Waldenstrom_Macroglobulinemia","name":"Waldenstrom Macroglobulinemia","kind":"Disorder","source_path":"kb/disorders/Waldenstrom_Macroglobulinemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Waldenstrom_Macroglobulinemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Waldenstrom_Macroglobulinemia.html#dataset-geo-gse70511"}],"context_names":["Waldenstrom Macroglobulinemia"],"disease_names":["Waldenstrom Macroglobulinemia"],"disease_name":"Waldenstrom Macroglobulinemia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Waldenstrom_Macroglobulinemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Waldenstrom_Macroglobulinemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Waldenstrom_Macroglobulinemia.html#dataset-geo-gse70511"]},{"id":"dataset:geo:gse70515","accession":"geo:GSE70515","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE70515","title":"Gene expression signature of bone lesion waldenstrom macroglobulinemia and myeloma","alternate_titles":[],"description":"Bone lesion in waldenstom macroglobulinemia (WM) is less common. In the present study, we compaired gene expresion signature of bone lesion in WM compaired to multiple myeloma (MM). In WM, APRIL and HBGB1 were up-regulated compaired to MM.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[7],"sample_count":7,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Waldenstrom Macroglobulinemia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Waldenstrom_Macroglobulinemia","name":"Waldenstrom Macroglobulinemia","kind":"Disorder","source_path":"kb/disorders/Waldenstrom_Macroglobulinemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Waldenstrom_Macroglobulinemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Waldenstrom_Macroglobulinemia.html#dataset-geo-gse70515"}],"context_names":["Waldenstrom Macroglobulinemia"],"disease_names":["Waldenstrom Macroglobulinemia"],"disease_name":"Waldenstrom Macroglobulinemia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Waldenstrom_Macroglobulinemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Waldenstrom_Macroglobulinemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Waldenstrom_Macroglobulinemia.html#dataset-geo-gse70515"]},{"id":"dataset:geo:gse70683","accession":"geo:GSE70683","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE70683","title":"Microarray expression data from three arterial tortuosity syndrome (ATS) patients' skin fibroblasts with recessive SLC2A10 mutations","alternate_titles":[],"description":"To screen for candidate genes that may contribute to the pathogenesis of ATS Transcriptome-wide expression profiling using the Affymetrix Gene 1.0 ST platform comparing the gene expression patterns of skin fibroblasts of three ATS patients with those of three healthy individuals","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:26376865"],"publication_contexts":[{"context_id":"disorder:Arterial_Tortuosity_Syndrome","publication":"PMID:26376865"}],"publication":"PMID:26376865","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/26376865","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Arterial Tortuosity Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Arterial_Tortuosity_Syndrome","name":"Arterial Tortuosity Syndrome","kind":"Disorder","source_path":"kb/disorders/Arterial_Tortuosity_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Arterial_Tortuosity_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Arterial_Tortuosity_Syndrome.html#dataset-geo-gse70683"}],"context_names":["Arterial Tortuosity Syndrome"],"disease_names":["Arterial Tortuosity Syndrome"],"disease_name":"Arterial Tortuosity Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Arterial_Tortuosity_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Arterial_Tortuosity_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Arterial_Tortuosity_Syndrome.html#dataset-geo-gse70683"]},{"id":"dataset:geo:gse70719","accession":"geo:GSE70719","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE70719","title":"Gene expression profiling of HOS (human osteosarcoma) cells exposed to fluoride","alternate_titles":[],"description":"Human osteosarcoma cells exposed to a sub-lethal fluoride concentration for 30 days, framed by its authors as a model of fluorosis. A cell line, not patient material.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE70719","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE70719","reference_title":"Gene expression profiling of HOS (human osteosarcoma) cells exposed to fluoride","supports":"SUPPORT","evidence_source":"OTHER","snippet":"To understand the molecular mechanism of fluoride induced toxicity gene expression profiling was performed on osteosarcoma cells (HOS). Cells were exposed to sub-lethal concentration of fluoride (8 ppm) for 30 days. Our result demonstrates that fluoride alters multiple biological pathways including bone development, osteoblast differentiation and apoptotic pathways.","explanation":"The design and the framing, from GEO's own summary. Graded OTHER as a repository record rather than a study result."}],"notes":[],"contexts":[{"id":"disorder:Skeletal_Fluorosis","name":"Skeletal Fluorosis","kind":"Disorder","source_path":"kb/disorders/Skeletal_Fluorosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Skeletal_Fluorosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Skeletal_Fluorosis.html#dataset-geo-gse70719"}],"context_names":["Skeletal Fluorosis"],"disease_names":["Skeletal Fluorosis"],"disease_name":"Skeletal Fluorosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Skeletal_Fluorosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Skeletal_Fluorosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Skeletal_Fluorosis.html#dataset-geo-gse70719"]},{"id":"dataset:geo:gse70783","accession":"geo:GSE70783","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE70783","title":"Genome-wide methylation profiles in primary intracranial germ cell tumors indicate primordial germ cell origin of germinoma [Illumina]","alternate_titles":[],"description":"The pathogenesis of intracranial germ cell tumors (iGCTs) is not yet fully uncovered despite exhaustive genomic analyses. By means of a genome-wide methylation analysis, we show that pure germinoma is characterized by global DNA low methylation, a unique epigenetic feature distinct from all other subtypes of iGCTs. The patterns of methylation strongly resemble that of primordial germ cells (PGC) at the migration phase, indicating the cells of origin. Unlike PGC, however, hypomethylation extends to LINE1 retrotransposon.","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[77],"sample_count":77,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:28078450"],"publication_contexts":[{"context_id":"disorder:Mixed_Germ_Cell_Tumor","publication":"PMID:28078450"}],"publication":"PMID:28078450","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/28078450","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Mixed Germ Cell Tumor (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Mixed_Germ_Cell_Tumor","name":"Mixed Germ Cell Tumor","kind":"Disorder","source_path":"kb/disorders/Mixed_Germ_Cell_Tumor.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mixed_Germ_Cell_Tumor.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Mixed_Germ_Cell_Tumor.html#dataset-geo-gse70783"}],"context_names":["Mixed Germ Cell Tumor"],"disease_names":["Mixed Germ Cell Tumor"],"disease_name":"Mixed Germ Cell Tumor","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Mixed_Germ_Cell_Tumor.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mixed_Germ_Cell_Tumor.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Mixed_Germ_Cell_Tumor.html#dataset-geo-gse70783"]},{"id":"dataset:geo:gse71058","accession":"geo:GSE71058","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE71058","title":"Gene expression profiling in dentate granule cells from patients with mesial temporal lobe epilepsy with or without hippocampal sclerosis","alternate_titles":[],"description":"Hippocampal sclerosis (HS) is the most common neuropathological finding of medically intractable cases of mesial temporal lobe epilepsy (MTLE), the most common form of partial epilepsy. Within the dentate gyrus, HS may be associated with granule cell dispersion and aberrant mossy fiber sprouting, and these pathological changes are accompanied by a range of molecular changes.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[22],"sample_count":22,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:26799155"],"publication_contexts":[{"context_id":"disorder:Mesial_Temporal_Lobe_Epilepsy_with_Hippocampal_Sclerosis","publication":"PMID:26799155"}],"publication":"PMID:26799155","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/26799155","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Mesial_Temporal_Lobe_Epilepsy_with_Hippocampal_Sclerosis","name":"Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis","kind":"Disorder","source_path":"kb/disorders/Mesial_Temporal_Lobe_Epilepsy_with_Hippocampal_Sclerosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mesial_Temporal_Lobe_Epilepsy_with_Hippocampal_Sclerosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Mesial_Temporal_Lobe_Epilepsy_with_Hippocampal_Sclerosis.html#dataset-geo-gse71058"}],"context_names":["Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis"],"disease_names":["Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis"],"disease_name":"Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Mesial_Temporal_Lobe_Epilepsy_with_Hippocampal_Sclerosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mesial_Temporal_Lobe_Epilepsy_with_Hippocampal_Sclerosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Mesial_Temporal_Lobe_Epilepsy_with_Hippocampal_Sclerosis.html#dataset-geo-gse71058"]},{"id":"dataset:geo:gse71172","accession":"geo:GSE71172","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE71172","title":"microRNA expression profiles from three arterial tortuosity syndrome (ATS) patients' skin fibroblasts with recessive SLC2A10 mutations [miRNA]","alternate_titles":[],"description":"To screen for potential miRNA that may contribute to the pathomechanisms of ATS miRNA expression profiling using the Affymetrix GeneChip® miRNA 3.0 Array comparing the miRNA expression changes of skin fibroblasts of three ATS patients with those of three healthy individuals","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:26376865"],"publication_contexts":[{"context_id":"disorder:Arterial_Tortuosity_Syndrome","publication":"PMID:26376865"}],"publication":"PMID:26376865","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/26376865","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Arterial Tortuosity Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Arterial_Tortuosity_Syndrome","name":"Arterial Tortuosity Syndrome","kind":"Disorder","source_path":"kb/disorders/Arterial_Tortuosity_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Arterial_Tortuosity_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Arterial_Tortuosity_Syndrome.html#dataset-geo-gse71172"}],"context_names":["Arterial Tortuosity Syndrome"],"disease_names":["Arterial Tortuosity Syndrome"],"disease_name":"Arterial Tortuosity Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Arterial_Tortuosity_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Arterial_Tortuosity_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Arterial_Tortuosity_Syndrome.html#dataset-geo-gse71172"]},{"id":"dataset:geo:gse71234","accession":"geo:GSE71234","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE71234","title":"Reversal of MECP2 duplication syndrome using genetic rescue and antisense oligonucleotides [ASO time point 2]","alternate_titles":[],"description":"MECP2 duplication syndrome, a childhood neurological disorder characterized by autism, intellectual disability, motor dysfunction, anxiety and epilepsy, is caused by a duplication on chromosome Xq28 spanning the MECP2 gene that results in doubling of MeCP2 levels. MECP2 overexpression in mice causes neurobehavioral and electroencephalographic defects similar to those of human patients, but the gross anatomy of the brain remains unaffected. We hypothesized that MECP2 duplication syndrome would be reversible and tested two methods to restore MeCP2 levels to normal: conditional genetic recombination and antisense oligonucleotide therapy.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[9],"sample_count":9,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:26605526"],"publication_contexts":[{"context_id":"disorder:MECP2_Duplication_Syndrome","publication":"PMID:26605526"}],"publication":"PMID:26605526","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/26605526","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for MECP2 Duplication Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:MECP2_Duplication_Syndrome","name":"MECP2 Duplication Syndrome","kind":"Disorder","source_path":"kb/disorders/MECP2_Duplication_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MECP2_Duplication_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/MECP2_Duplication_Syndrome.html#dataset-geo-gse71234"}],"context_names":["MECP2 Duplication Syndrome"],"disease_names":["MECP2 Duplication Syndrome"],"disease_name":"MECP2 Duplication Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/MECP2_Duplication_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MECP2_Duplication_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/MECP2_Duplication_Syndrome.html#dataset-geo-gse71234"]},{"id":"dataset:geo:gse71912","accession":"geo:GSE71912","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE71912","title":"Mutations in the NOTCH pathway regulator MIB1 cause left ventricular noncompaction cardiomyopathy","alternate_titles":[],"description":"Public LVNC transcriptomic dataset reused in integrative bioinformatic analyses of myocardial disease mechanisms and candidate biomarkers.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression 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cardiomyopathy.","supports":"SUPPORT","evidence_source":"COMPUTATIONAL","snippet":"The datasets GSE71912 and GSE113251 of left ventricular noncompaction cardiomyopathy were downloaded from the gene expression omnibus (GEO) database generated from GPL13912 and GPL11002 platforms.","explanation":"Supports GSE71912 as a public LVNC dataset used for disease-mechanism discovery."}],"notes":[],"contexts":[{"id":"disorder:Left_Ventricular_Noncompaction","name":"Left ventricular noncompaction","kind":"Disorder","source_path":"kb/disorders/Left_Ventricular_Noncompaction.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Left_Ventricular_Noncompaction.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Left_ventricular_noncompaction.html#dataset-geo-gse71912"}],"context_names":["Left ventricular noncompaction"],"disease_names":["Left ventricular noncompaction"],"disease_name":"Left ventricular noncompaction","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Left_Ventricular_Noncompaction.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Left_Ventricular_Noncompaction.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Left_ventricular_noncompaction.html#dataset-geo-gse71912"]},{"id":"dataset:geo:gse71957","accession":"geo:GSE71957","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE71957","title":"Epigenetic profiling in CD4 and CD8 T cells from Graves disease patients reveals changes in genes associated with T cell receptor signaling","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["MULTI_OMICS"],"data_type_labels":["Multi 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Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Graves_Disease","name":"Graves' Disease","kind":"Disorder","source_path":"kb/disorders/Graves_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Graves_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Graves'_Disease.html#dataset-geo-gse71957"}],"context_names":["Graves' Disease"],"disease_names":["Graves' Disease"],"disease_name":"Graves' Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Graves_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Graves_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Graves'_Disease.html#dataset-geo-gse71957"]},{"id":"dataset:geo:gse71997","accession":"geo:GSE71997","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE71997","title":"Insights into ulcerative colitis and ileal pouchitis from a model of stasis-induced enteric dysbiosis and genetic susceptibility","alternate_titles":[],"description":"Gut dysbiosis and host genetics are implicated as causative factors in inflammatory bowel disease, yet mechanistic insights are lacking. Longitudinal analysis of ulcerative colitis patients following total colectomy with ileal anal anastomosis (IPAA) where >50% develop pouchitis, offers a unique setting to examine cause vs. effect. To recapitulate human IPAA, we employed a mouse model of surgically-created blind self-filling (SFL) and self-emptying (SEL) ileal loops. SFL exhibit fecal stasis due to directional peristalsis motility oriented towards away from the loop end, whereas SEL remain empty.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[25],"sample_count":25,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:27079612"],"publication_contexts":[{"context_id":"disorder:Pouchitis","publication":"PMID:27079612"}],"publication":"PMID:27079612","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/27079612","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Pouchitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Pouchitis","name":"Pouchitis","kind":"Disorder","source_path":"kb/disorders/Pouchitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pouchitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pouchitis.html#dataset-geo-gse71997"}],"context_names":["Pouchitis"],"disease_names":["Pouchitis"],"disease_name":"Pouchitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Pouchitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pouchitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Pouchitis.html#dataset-geo-gse71997"]},{"id":"dataset:geo:gse72748","accession":"geo:GSE72748","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE72748","title":"Transcriptomes of peripheral blood mononuclear cells from a Guillain-Barre Syndrome patient and her healthy twin sampled at three different points of the disease evolution","alternate_titles":[],"description":"Guillain-Barré syndrome (GBS) is an immune-mediated peripheral neuropathy that debilitates the voluntary and autonomous response of the patient. In this study the transcriptome of peripheral blood mononuclear cells from a GBS patient and her healthy twin were compared to discover possible correlates of disease progression and recovery.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:26718337"],"publication_contexts":[{"context_id":"disorder:Guillain_Barre_Syndrome","publication":"PMID:26718337"}],"publication":"PMID:26718337","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/26718337","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Guillain-Barre Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Guillain_Barre_Syndrome","name":"Guillain-Barre Syndrome","kind":"Disorder","source_path":"kb/disorders/Guillain_Barre_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Guillain_Barre_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Guillain-Barre_Syndrome.html#dataset-geo-gse72748"}],"context_names":["Guillain-Barre Syndrome"],"disease_names":["Guillain-Barre Syndrome"],"disease_name":"Guillain-Barre Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Guillain_Barre_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Guillain_Barre_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Guillain-Barre_Syndrome.html#dataset-geo-gse72748"]},{"id":"dataset:geo:gse72946","accession":"geo:GSE72946","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE72946","title":"Cathelicidin insufficiency in patients with fatal leptospirosis","alternate_titles":[],"description":"Human whole-blood transcriptome microarray dataset in acute leptospirosis, designed to identify molecular signatures associated with case fatality.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[33],"sample_count":33,"conditions":["acute leptospirosis","convalescent leptospirosis","healthy volunteers"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:27812211"],"publication_contexts":[{"context_id":"disorder:Leptospirosis","publication":"PMID:27812211"}],"publication":"PMID:27812211","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/27812211","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"GEO:GSE72946","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE72946","reference_title":"Cathelicidin insufficiency in patients with fatal leptospirosis","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"Whole blood transcriptional profiling of Brazilian patients with acute leptospirosis to identify mechanisms associated with case fatality","explanation":"Supports use of this human dataset for severity-linked host-response analyses."}],"notes":[],"contexts":[{"id":"disorder:Leptospirosis","name":"Leptospirosis","kind":"Disorder","source_path":"kb/disorders/Leptospirosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Leptospirosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Leptospirosis.html#dataset-geo-gse72946"}],"context_names":["Leptospirosis"],"disease_names":["Leptospirosis"],"disease_name":"Leptospirosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Leptospirosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Leptospirosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Leptospirosis.html#dataset-geo-gse72946"]},{"id":"dataset:geo:gse73263","accession":"geo:GSE73263","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE73263","title":"A Mutation in LTBP2 Causes Congenital Glaucoma in Domestic Cats (Felis catus)","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9685","label":"Felis catus","display_label":"domestic cat","url":"http://purl.obolibrary.org/obo/NCBITaxon_9685"}],"organism_labels":["Felis catus"],"organism_label":"Felis catus","sample_types":[],"sample_type_labels":[],"sample_counts":[2],"sample_count":2,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:27149523"],"publication_contexts":[{"context_id":"disorder:Congenital_Glaucoma","publication":"PMID:27149523"}],"publication":"PMID:27149523","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/27149523","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Naturally occurring feline primary congenital glaucoma segregating an LTBP2 mutation, from a breeding colony established for the trait -- directly the GLC3C/GLC3D mechanism curated here, in a spontaneous large-eye model rather than an engineered rodent one. Accession, title, organism, and sample count verified against NCBI E-utilities on 2026-08-20; the values are GEO's own."],"contexts":[{"id":"disorder:Congenital_Glaucoma","name":"Congenital Glaucoma","kind":"Disorder","source_path":"kb/disorders/Congenital_Glaucoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Congenital_Glaucoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Congenital_Glaucoma.html#dataset-geo-gse73263"}],"context_names":["Congenital Glaucoma"],"disease_names":["Congenital Glaucoma"],"disease_name":"Congenital Glaucoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Congenital_Glaucoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Congenital_Glaucoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Congenital_Glaucoma.html#dataset-geo-gse73263"]},{"id":"dataset:geo:gse73336","accession":"geo:GSE73336","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE73336","title":"Transplantation of gastric organoid-derived spasmolytic polypeptide/TFF2-expressing metaplasia (SPEM) cell lineage promotes ulcer repair in the aged stomach","alternate_titles":[],"description":"Background & Aims: Spasmolytic polypeptide/TFF2-expressing metaplasia (SPEM) is known to emerge following parietal cell loss and during Helicobacter pylori infection, however its role in gastric ulcer repair is unknown. Therefore, we sought to investigate if SPEM plays a role in epithelial regeneration. Methods: Acetic acid ulcers were induced in young (2-3 months) C57BL/6 mice to determine the quality of ulcer repair. Gastric tissue was collected and analyzed to determine the expression of SPEM within the regenerating epithelium. As a comparison to native tissue the expression of SPEM was also identified within cultured gastric mouse-derived organoids.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[10],"sample_count":10,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:32147965"],"publication_contexts":[{"context_id":"disorder:Gastric_Ulcer","publication":"PMID:32147965"}],"publication":"PMID:32147965","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32147965","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Gastric Ulcer (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Gastric_Ulcer","name":"Gastric Ulcer","kind":"Disorder","source_path":"kb/disorders/Gastric_Ulcer.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Gastric_Ulcer.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Gastric_Ulcer.html#dataset-geo-gse73336"}],"context_names":["Gastric Ulcer"],"disease_names":["Gastric Ulcer"],"disease_name":"Gastric Ulcer","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Gastric_Ulcer.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Gastric_Ulcer.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Gastric_Ulcer.html#dataset-geo-gse73336"]},{"id":"dataset:geo:gse73962","accession":"geo:GSE73962","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE73962","title":"Comparative genomic analyses of the human NPHP1 locus reveal complex genomic architecture and its regional evolution in primates","alternate_titles":[],"description":"Many loci in the human genome harbor complex genomic structures that can result in susceptibility to genomic rearrangements leading to various genomic disorders. Nephronophthisis 1 (NPHP1, MIM# 256100) is an autosomal recessive disorder that can be caused by defects of NPHP1; the gene maps within the human 2q13 region where low copy repeats (LCRs) are abundant. Loss of function of NPHP1 is responsible for approximately 85% of the NPHP1 cases - about 80% of such individuals carry a large recurrent homozygous NPHP1 deletion that occurs via non-allelic homologous recombination (NAHR) between two flanking directly oriented ~45 kb LCRs.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[32],"sample_count":32,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:26641089"],"publication_contexts":[{"context_id":"disorder:Nephronophthisis","publication":"PMID:26641089"}],"publication":"PMID:26641089","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/26641089","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Nephronophthisis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Nephronophthisis","name":"Nephronophthisis","kind":"Disorder","source_path":"kb/disorders/Nephronophthisis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Nephronophthisis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Nephronophthisis.html#dataset-geo-gse73962"}],"context_names":["Nephronophthisis"],"disease_names":["Nephronophthisis"],"disease_name":"Nephronophthisis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Nephronophthisis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Nephronophthisis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Nephronophthisis.html#dataset-geo-gse73962"]},{"id":"dataset:geo:gse7527","accession":"geo:GSE7527","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE7527","title":"Array CGH in congenital heart disease","alternate_titles":[],"description":"Sub-megabase-resolution BAC array comparative genomic hybridization screen of 104 patients with congenital heart disease as the sole abnormality at diagnosis, plus some of their parents, searching for DNA copy number changes in non-syndromic CHD.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[119],"sample_count":119,"conditions":["non-syndromic congenital heart disease"],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:4173","label":"GATA4","display_label":"GATA4","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/4173"}],"genes":["GATA4"],"platforms":["BAC array CGH (sub-megabase resolution)"],"platform":"BAC array CGH (sub-megabase resolution)","publications":["PMID:18713793"],"publication_contexts":[{"context_id":"disorder:Ebstein_Anomaly","publication":"PMID:18713793"}],"publication":"PMID:18713793","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/18713793","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Relevance triage: the cohort is non-syndromic congenital heart disease generally, not Ebstein anomaly specifically, but exactly one sample in the GEO series metadata is annotated with an Ebstein anomaly diagnosis. It is included because copy number variation is the one genetic mechanism with reproducible support in Ebstein anomaly (1p36 and 8p23.1 deletions), and this is the closest available primary copy-number dataset; the single Ebstein sample means it cannot support any Ebstein-specific quantitative claim. No Ebstein-anomaly-specific transcriptomic, proteomic, or copy-number dataset exists in GEO. The other candidates surfaced by dataset discovery were gene-only matches on MYH7, GATA4, and NKX2-5 that are about hypertrophic cardiomyopathy, ovarian cancer, and transcription-factor binding respectively, and were rejected as Named Entity Confusion."],"contexts":[{"id":"disorder:Ebstein_Anomaly","name":"Ebstein Anomaly","kind":"Disorder","source_path":"kb/disorders/Ebstein_Anomaly.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ebstein_Anomaly.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Ebstein_Anomaly.html#dataset-geo-gse7527"}],"context_names":["Ebstein Anomaly"],"disease_names":["Ebstein Anomaly"],"disease_name":"Ebstein Anomaly","same_context_model_ids":["model:kb/disorders/Ebstein_Anomaly.yaml:Mouse and canine models of tricuspid valve malformation"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Ebstein_Anomaly.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ebstein_Anomaly.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Ebstein_Anomaly.html#dataset-geo-gse7527"]},{"id":"dataset:geo:gse75545","accession":"geo:GSE75545","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE75545","title":"Urine-sample-derived human induced pluripotent stem cells as a model to study PCSK9-mediated autosomal dominant hypercholesterolemia","alternate_titles":[],"description":"GSE75545 contains ten expression arrays comparing urine-derived progenitor cells with reprogrammed iPSCs from a control donor and an S127R carrier: two progenitor samples per donor and three iPSC clones per donor. It does not contain hepatocyte-like-cell treatment arrays or the loss-of-function donor arrays described elsewhere in the publication.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:26586530"],"publication_contexts":[{"context_id":"disorder:Autosomal_Dominant_Hypercholesterolemia_3","publication":"PMID:26586530"}],"publication":"PMID:26586530","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/26586530","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:26586530","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/26586530","reference_title":"Urine-sample-derived human induced pluripotent stem cells as a model to study PCSK9-mediated autosomal dominant hypercholesterolemia.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"A transcriptomic analysis was performed and confirmed the global gene-expression profile modification between two control Ucell lines, two PCSK9-S127R Ucell lines and three clones of each UhiPSC line generated","explanation":"The full-text reprogramming analysis defines the deposited expression experiment; clone counts do not represent independent patients."}],"notes":["Sample-level GEO design was checked against the publication Methods and Figure 2. The GEO series summary reproduces the broader study abstract, whose hepatocyte and drug experiments extend beyond this deposited microarray series."],"contexts":[{"id":"disorder:Autosomal_Dominant_Hypercholesterolemia_3","name":"Autosomal Dominant Hypercholesterolemia 3","kind":"Disorder","source_path":"kb/disorders/Autosomal_Dominant_Hypercholesterolemia_3.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autosomal_Dominant_Hypercholesterolemia_3.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Dominant_Hypercholesterolemia_3.html#dataset-geo-gse75545"}],"context_names":["Autosomal Dominant Hypercholesterolemia 3"],"disease_names":["Autosomal Dominant Hypercholesterolemia 3"],"disease_name":"Autosomal Dominant Hypercholesterolemia 3","same_context_model_ids":["model:kb/disorders/Autosomal_Dominant_Hypercholesterolemia_3.yaml:Urine-derived iPSC hepatocyte-like cells from a PCSK9 S127R carrier (HLC-S127R)"],"candidate_model_ids":["model:kb/disorders/Autosomal_Dominant_Hypercholesterolemia_3.yaml:Urine-derived iPSC hepatocyte-like cells from a PCSK9 S127R carrier (HLC-S127R)"],"association_basis":"Same publication as a NAM (candidate)","nam_disease_context":"Same publication as a NAM (candidate)","source_paths":["kb/disorders/Autosomal_Dominant_Hypercholesterolemia_3.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autosomal_Dominant_Hypercholesterolemia_3.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Dominant_Hypercholesterolemia_3.html#dataset-geo-gse75545"]},{"id":"dataset:geo:gse75704","accession":"geo:GSE75704","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE75704","title":"Genome-wide DNA methylation profiling in progressive supranuclear palsy (PSP)","alternate_titles":[],"description":"Genome wide Methylation profiling of DNA extracted from post-mortem forebrains of PSP patients (n=94) and of controls (n=72). The Illumina Infinium HumanMethylation450 BeadChip was used representing 485,000 potentially methylated CpG sites throughout the genome.","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[166],"sample_count":166,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:30050033"],"publication_contexts":[{"context_id":"disorder:Progressive_Supranuclear_Palsy","publication":"PMID:30050033"}],"publication":"PMID:30050033","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/30050033","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Progressive Supranuclear Palsy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Progressive_Supranuclear_Palsy","name":"Progressive Supranuclear Palsy","kind":"Disorder","source_path":"kb/disorders/Progressive_Supranuclear_Palsy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Progressive_Supranuclear_Palsy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Progressive_Supranuclear_Palsy.html#dataset-geo-gse75704"}],"context_names":["Progressive Supranuclear Palsy"],"disease_names":["Progressive Supranuclear Palsy"],"disease_name":"Progressive Supranuclear Palsy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Progressive_Supranuclear_Palsy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Progressive_Supranuclear_Palsy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Progressive_Supranuclear_Palsy.html#dataset-geo-gse75704"]},{"id":"dataset:geo:gse75713","accession":"geo:GSE75713","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE75713","title":"GAA deficiency in Pompe disease is alleviated by exon inclusion in iPS cell-derived skeletal muscle cells","alternate_titles":[],"description":"Microarray profiling of iPSC-derived skeletal muscle cells from Pompe disease patients in which GAA deficiency is corrected by splice modulation promoting exon inclusion - the in vitro counterpart of the leaky-splicing mechanism curated here.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[6],"sample_count":6,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:4065","label":"GAA","display_label":"GAA","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/4065"}],"genes":["GAA"],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Discovered via `just discover-datasets` as a GENE_ONLY candidate and retained after manual relevance triage: the GEO title and summary describe splice-based exon-inclusion correction of GAA deficiency in a patient iPSC skeletal-muscle model, which is the LOPD splicing mechanism. The GEO record carries no linked publication, so no `publication:` is asserted. Verified with `just verify-datasets`. Retrieved 2026-08-18."],"contexts":[{"id":"disorder:Late-Onset_Pompe_Disease","name":"Late-Onset Pompe Disease","kind":"Disorder","source_path":"kb/disorders/Late-Onset_Pompe_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Late-Onset_Pompe_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Late-Onset_Pompe_Disease.html#dataset-geo-gse75713"}],"context_names":["Late-Onset Pompe Disease"],"disease_names":["Late-Onset Pompe Disease"],"disease_name":"Late-Onset Pompe Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Late-Onset_Pompe_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Late-Onset_Pompe_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Late-Onset_Pompe_Disease.html#dataset-geo-gse75713"]},{"id":"dataset:geo:gse75838","accession":"geo:GSE75838","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE75838","title":"Absence of integrin α3 modulates the integrin landscape of human keratinocytes","alternate_titles":[],"description":"Human keratinocyte microarray dataset built from patient-derived ITGA3 loss-of-function cells and matched experimental controls, modeling the junctional epidermolysis bullosa spectrum associated with integrin alpha-3 deficiency.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene 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been recently disclosed in patients with interstitial lung disease, congenital nephrotic syndrome and junctional epidermolysis bullosa","explanation":"Establishes the dataset's direct link to a human JEB-spectrum disorder caused by ITGA3 deficiency."},{"reference":"GEO:GSE75838","reference_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE75838","reference_title":"Absence of integrin α3 modulates the integrin landscape of human keratinocytes","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Here we employed authentic human keratinocytes bearing a naturally occurring integrin α3 loss-of-function mutation as a prototype","explanation":"Confirms this is a patient-derived human keratinocyte resource for dissecting adhesion defects relevant to junctional EB."}],"notes":[],"contexts":[{"id":"disorder:Junctional_Epidermolysis_Bullosa","name":"Junctional Epidermolysis Bullosa","kind":"Disorder","source_path":"kb/disorders/Junctional_Epidermolysis_Bullosa.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Junctional_Epidermolysis_Bullosa.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Junctional_Epidermolysis_Bullosa.html#dataset-geo-gse75838"}],"context_names":["Junctional Epidermolysis Bullosa"],"disease_names":["Junctional Epidermolysis Bullosa"],"disease_name":"Junctional Epidermolysis Bullosa","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Junctional_Epidermolysis_Bullosa.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Junctional_Epidermolysis_Bullosa.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Junctional_Epidermolysis_Bullosa.html#dataset-geo-gse75838"]},{"id":"dataset:geo:gse75886","accession":"geo:GSE75886","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE75886","title":"Molecular patterns of diffuse and nodular parathyroid hyperplasia in long-term hemodialysis","alternate_titles":[],"description":"Secondary hyperparathyroidism is well known complication manifested in end-stage renal disease (ESRD). Both nodular and diffuse parathyreoid hyperplasia occur in ESRD patients. Distinct molecular mechanisms involved in parathyreoid hyperplasia remain poorly understood. Microarray screening proved homogeneity of gene transcripts in hemodialysis patients as compared to transplant cohort and primary hyperparathyreoidism, therefore further studies were performed in hemodialysis patints only.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[29],"sample_count":29,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:27600827"],"publication_contexts":[{"context_id":"disorder:Parathyroid_Hyperplasia","publication":"PMID:27600827"}],"publication":"PMID:27600827","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/27600827","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Parathyroid Hyperplasia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Parathyroid_Hyperplasia","name":"Parathyroid Hyperplasia","kind":"Disorder","source_path":"kb/disorders/Parathyroid_Hyperplasia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Parathyroid_Hyperplasia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Parathyroid_Hyperplasia.html#dataset-geo-gse75886"}],"context_names":["Parathyroid Hyperplasia"],"disease_names":["Parathyroid Hyperplasia"],"disease_name":"Parathyroid Hyperplasia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Parathyroid_Hyperplasia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Parathyroid_Hyperplasia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Parathyroid_Hyperplasia.html#dataset-geo-gse75886"]},{"id":"dataset:geo:gse76438","accession":"geo:GSE76438","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE76438","title":"Uncovering obsessive-compulsive disorder risk genes in a pediatric cohort by high-resolution analysis of copy number variation.","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["GWAS"],"data_type_labels":["Genome-wide association study"],"data_type_label":"Genome-wide association study","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[661],"sample_count":661,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:27777633"],"publication_contexts":[{"context_id":"disorder:Obsessive-Compulsive_Disorder","publication":"PMID:27777633"}],"publication":"PMID:27777633","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/27777633","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Obsessive-Compulsive Disorder (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Obsessive-Compulsive_Disorder","name":"Obsessive-Compulsive Disorder","kind":"Disorder","source_path":"kb/disorders/Obsessive-Compulsive_Disorder.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Obsessive-Compulsive_Disorder.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Obsessive-Compulsive_Disorder.html#dataset-geo-gse76438"}],"context_names":["Obsessive-Compulsive Disorder"],"disease_names":["Obsessive-Compulsive Disorder"],"disease_name":"Obsessive-Compulsive Disorder","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Obsessive-Compulsive_Disorder.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Obsessive-Compulsive_Disorder.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Obsessive-Compulsive_Disorder.html#dataset-geo-gse76438"]},{"id":"dataset:geo:gse77087","accession":"geo:GSE77087","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE77087","title":"Nasopharyngeal microbiota, host transcriptome and disease severity in children with respiratory syncytial virus infection","alternate_titles":[],"description":"Rationale: Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections and hospitalizations in infants worldwide. Known risk factors, however, incompletely explain the variability of RSV disease severity among children. We postulate that severity of RSV infection is influenced in part by modulation of the host immune response by the local microbial ecosystem at the time of infection. Objectives: To define whether different nasopharyngeal microbiota profiles are associated with distinct host transcriptome profiles and severity in children with RSV infection.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[104],"sample_count":104,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:27135599"],"publication_contexts":[{"context_id":"disorder:Respiratory_Syncytial_Virus_Infection","publication":"PMID:27135599"}],"publication":"PMID:27135599","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/27135599","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Respiratory Syncytial Virus Infection (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Respiratory_Syncytial_Virus_Infection","name":"Respiratory Syncytial Virus Infection","kind":"Disorder","source_path":"kb/disorders/Respiratory_Syncytial_Virus_Infection.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Respiratory_Syncytial_Virus_Infection.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Respiratory_Syncytial_Virus_Infection.html#dataset-geo-gse77087"}],"context_names":["Respiratory Syncytial Virus Infection"],"disease_names":["Respiratory Syncytial Virus Infection"],"disease_name":"Respiratory Syncytial Virus Infection","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Respiratory_Syncytial_Virus_Infection.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Respiratory_Syncytial_Virus_Infection.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Respiratory_Syncytial_Virus_Infection.html#dataset-geo-gse77087"]},{"id":"dataset:geo:gse77253","accession":"geo:GSE77253","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE77253","title":"Wiskott-Aldrich Syndrome-causative mutations disrupt alternative splicing and promote gene networks predisposed to hematologic malignancies","alternate_titles":[],"description":"Wiskott-Aldrich syndrome (WAS) is characterized by X-linked thrombocytopenia, eczema, immunodeficiency, recurrent infections and increased risk of autoimmunity and malignancies. WAS is caused by mutations in the WAS gene, which encodes the exclusively hematopoietic WAS protein (WASp) that is classically characterized as aν actin nucleator. However, disruption of F-actin polymerization by WAS mutations can not account for many aspects of WAS pathogenesis. Ignorance of other functions of WASP precludes in-depth understanding of the pathogenic effects of mutant WASP, and therefore hampers development of effective therapy.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[14],"sample_count":14,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Wiskott-Aldrich syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Wiskott_Aldrich_Syndrome","name":"Wiskott-Aldrich syndrome","kind":"Disorder","source_path":"kb/disorders/Wiskott_Aldrich_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Wiskott_Aldrich_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Wiskott-Aldrich_syndrome.html#dataset-geo-gse77253"}],"context_names":["Wiskott-Aldrich syndrome"],"disease_names":["Wiskott-Aldrich syndrome"],"disease_name":"Wiskott-Aldrich syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Wiskott_Aldrich_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Wiskott_Aldrich_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Wiskott-Aldrich_syndrome.html#dataset-geo-gse77253"]},{"id":"dataset:geo:gse77753","accession":"geo:GSE77753","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE77753","title":"Microarray expression data from five Ehlers-Danlos Syndrome Hypermobility type/Joint Hypermobility Syndrome (EDS-HT/JHS) patients' skin fibroblasts","alternate_titles":[],"description":"Affymetrix Gene 1.0 ST transcriptome profiling of skin fibroblasts from five JHS/EDS-HT (legacy hEDS nomenclature) patients versus six healthy individuals. 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10-20 ml, n = 5; >50 ml, n = 3) and minimally cystic tissue (MCT, n = 5) from five PKD1 human polycystic kidneys using Affymetrix HG-U133 Plus 2.0 arrays.","explanation":"Describes the PKD1 cyst epithelium microarray experiment underlying GSE7869."}],"notes":["Public ADPKD microarray dataset frequently used to study cystogenesis-related signaling changes."],"contexts":[{"id":"disorder:Polycystic_Kidney_Disease","name":"Polycystic Kidney Disease","kind":"Disorder","source_path":"kb/disorders/Polycystic_Kidney_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Polycystic_Kidney_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Polycystic_Kidney_Disease.html#dataset-geo-gse7869"}],"context_names":["Polycystic Kidney Disease"],"disease_names":["Polycystic Kidney Disease"],"disease_name":"Polycystic Kidney Disease","same_context_model_ids":["model:kb/disorders/Polycystic_Kidney_Disease.yaml:ADPKD kidney organoid cystogenesis model","model:kb/disorders/Polycystic_Kidney_Disease.yaml:Adult ADPKD kidney tubuloid model","model:kb/disorders/Polycystic_Kidney_Disease.yaml:ARPKD organoid-on-chip mechanosensing model"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Polycystic_Kidney_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Polycystic_Kidney_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Polycystic_Kidney_Disease.html#dataset-geo-gse7869"]},{"id":"dataset:geo:gse79079","accession":"geo:GSE79079","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE79079","title":"β-glucans are Masked but Contribute to Pulmonary Inflammation During Pneumocystis Pneumonia","alternate_titles":[],"description":"β-glucans, which can activate innate immune responses, are a major component in the cell wall of the cyst form of Pneumocystis. 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For 3 species, including P. jirovecii, which causes Pneumocystis pneumonia (PCP) in humans, P. carinii, and P. murina, β-1,3 glucans were masked in most organisms, as demonstrated by increased exposure following trypsin treatment.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[11],"sample_count":11,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:27324243"],"publication_contexts":[{"context_id":"disorder:Pneumocystis_Pneumonia","publication":"PMID:27324243"}],"publication":"PMID:27324243","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/27324243","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Pneumocystis Pneumonia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. 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It is nonetheless the closest existing template for the longitudinal study that gap needs."],"contexts":[{"id":"disorder:MELAS_Syndrome","name":"MELAS Syndrome","kind":"Disorder","source_path":"kb/disorders/MELAS_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MELAS_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/MELAS_Syndrome.html#dataset-geo-gse89066"}],"context_names":["MELAS Syndrome"],"disease_names":["MELAS Syndrome"],"disease_name":"MELAS Syndrome","same_context_model_ids":["model:kb/disorders/MELAS_Syndrome.yaml:m.3243A>G patient iPSC-derived neurons"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/MELAS_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MELAS_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/MELAS_Syndrome.html#dataset-geo-gse89066"]},{"id":"dataset:geo:gse89420","accession":"geo:GSE89420","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE89420","title":"Surveillance of rRNA synthesis by an RNA helicase mediates tissue-specific developmental disorders","alternate_titles":[],"description":"Ten human HeLa samples profiling DDX21/TCOF1 chromatin occupancy and DDX21 RNA binding under TCOF1 knockdown, RNA polymerase I inhibition, or actinomycin D treatment.","alternate_descriptions":[],"data_types":["MULTI_OMICS_PERTURBATION"],"data_type_labels":["Multi Omics Perturbation"],"data_type_label":"Multi Omics Perturbation","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[10],"sample_count":10,"conditions":["siTCOF1 and control HeLa chromatin profiling","RNA polymerase I inhibition and control","actinomycin D and DMSO DDX21 irCLIP"],"exposure_terms":[],"exposures":[],"gene_terms":[{"id":"hgnc:11654","label":"TCOF1","display_label":"TCOF1","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/11654"}],"genes":["TCOF1"],"platforms":["ChIP-seq and DDX21 irCLIP"],"platform":"ChIP-seq and DDX21 irCLIP","publications":["PMID:29364875"],"publication_contexts":[{"context_id":"disorder:Treacher_Collins_Syndrome","publication":"PMID:29364875"}],"publication":"PMID:29364875","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/29364875","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"url:https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE89420","reference_url":null,"reference_title":"GEO Accession viewer","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"HeLa DDX21 ChIP-seq in siTCOF1","explanation":"The GEO record verifies the TCOF1-knockdown DDX21 chromatin-profiling sample in HeLa cells."},{"reference":"url:https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE89420","reference_url":null,"reference_title":"GEO Accession viewer","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"HeLa DDX21 ChIP-seq in iPol I treated cells","explanation":"The GEO sample list independently verifies the RNA-polymerase-I-inhibition chromatin-profiling arm."},{"reference":"url:https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE89420","reference_url":null,"reference_title":"GEO Accession viewer","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"DDX21 irCLIP from HeLa with ActD Biological replicate 1","explanation":"The GEO sample list verifies the DDX21 RNA-binding arm under actinomycin-D treatment in HeLa cells."}],"notes":["Mechanistically relevant but not a patient-derived or cranial-neural-crest dataset: all deposited samples are HeLa perturbation experiments. It can support TCOF1/DDX21 nucleolar-stress analysis but cannot establish a disease-specific human craniofacial expression signature. Gene-only cancer datasets returned by discovery were excluded."],"contexts":[{"id":"disorder:Treacher_Collins_Syndrome","name":"Treacher Collins Syndrome","kind":"Disorder","source_path":"kb/disorders/Treacher_Collins_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Treacher_Collins_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Treacher_Collins_Syndrome.html#dataset-geo-gse89420"}],"context_names":["Treacher Collins Syndrome"],"disease_names":["Treacher Collins Syndrome"],"disease_name":"Treacher Collins Syndrome","same_context_model_ids":["model:kb/disorders/Treacher_Collins_Syndrome.yaml:TCOF1-Haploinsufficient Human Pluripotent Stem Cell-Derived Neural Crest Model"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Treacher_Collins_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Treacher_Collins_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Treacher_Collins_Syndrome.html#dataset-geo-gse89420"]},{"id":"dataset:geo:gse93235","accession":"geo:GSE93235","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE93235","title":"Net silencing by let-7i in Postural Tachycardia Syndrome","alternate_titles":[],"description":"While strongly implicated in Postural Tachycardia Syndrome (POTS), considerable controversy exists regarding norepinephrine transporter (NET) loss-of-function. POTS is characterized by the clinical symptoms of orthostatic intolerance, light-headedness, tachycardia and syncope or near syncope with upright posture. Abnormal sympathetic nervous system activity is typical, of a type which suggests dysfunction of the NET, with evidence the gene responsible is under tight epigenetic control. Using RNA of isolated chromatin combined with sequencing (RICh-Seq) we show let7i miRNA suppresses NET by MeCP2. Vorinostat restores epigenetic control and NET expression in POTS.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[9],"sample_count":9,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:28352654"],"publication_contexts":[{"context_id":"disorder:Postural_Orthostatic_Tachycardia_Syndrome","publication":"PMID:28352654"}],"publication":"PMID:28352654","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/28352654","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Postural Orthostatic Tachycardia Syndrome (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Postural_Orthostatic_Tachycardia_Syndrome","name":"Postural Orthostatic Tachycardia Syndrome","kind":"Disorder","source_path":"kb/disorders/Postural_Orthostatic_Tachycardia_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Postural_Orthostatic_Tachycardia_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Postural_Orthostatic_Tachycardia_Syndrome.html#dataset-geo-gse93235"}],"context_names":["Postural Orthostatic Tachycardia Syndrome"],"disease_names":["Postural Orthostatic Tachycardia Syndrome"],"disease_name":"Postural Orthostatic Tachycardia Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Postural_Orthostatic_Tachycardia_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Postural_Orthostatic_Tachycardia_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Postural_Orthostatic_Tachycardia_Syndrome.html#dataset-geo-gse93235"]},{"id":"dataset:geo:gse93291","accession":"geo:GSE93291","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE93291","title":"A new molecular assay for the proliferation signature in mantle cell lymphoma applicable to formalin-fixed paraffin-embedded biopsies","alternate_titles":[],"description":"GEO microarray cohort of mantle cell lymphoma samples used for coexpression-network analysis, prognostic modeling, and survival prediction.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":["mantle cell lymphoma"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["GEO"],"platform":"GEO","publications":["PMID:32219041"],"publication_contexts":[{"context_id":"disorder:Mantle_Cell_Lymphoma","publication":"PMID:32219041"}],"publication":"PMID:32219041","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/32219041","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:32219041","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/32219041","reference_title":"Identification of key gene modules and hub genes of human mantle cell lymphoma by coexpression network analysis.","supports":"SUPPORT","evidence_source":"COMPUTATIONAL","snippet":"METHODS: The microarray dataset GSE93291 was downloaded from the Gene Expression Omnibus database.","explanation":"This explicitly identifies GSE93291 as a GEO mantle cell lymphoma microarray dataset used for transcriptomic network analysis."},{"reference":"PMID:35052318","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/35052318","reference_title":"Artificial Intelligence Analysis of Gene Expression Predicted the Overall Survival of Mantle Cell Lymphoma and a Large Pan-Cancer Series.","supports":"SUPPORT","evidence_source":"COMPUTATIONAL","snippet":"First, we analyzed a series of 123 cases (GSE93291).","explanation":"This independent analysis confirms reuse of GSE93291 as a mantle cell lymphoma gene-expression cohort for survival modeling."}],"notes":["Published reanalyses report 121 to 123 mantle cell lymphoma cases from this accession, reflecting analysis-specific filtering rather than a difference in disease context."],"contexts":[{"id":"disorder:Mantle_Cell_Lymphoma","name":"Mantle Cell Lymphoma","kind":"Disorder","source_path":"kb/disorders/Mantle_Cell_Lymphoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mantle_Cell_Lymphoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Mantle_Cell_Lymphoma.html#dataset-geo-gse93291"}],"context_names":["Mantle Cell Lymphoma"],"disease_names":["Mantle Cell Lymphoma"],"disease_name":"Mantle Cell Lymphoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Mantle_Cell_Lymphoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Mantle_Cell_Lymphoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Mantle_Cell_Lymphoma.html#dataset-geo-gse93291"]},{"id":"dataset:geo:gse93713","accession":"geo:GSE93713","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE93713","title":"Expression data from SCA3 and genetically corrected iPSCs","alternate_titles":[],"description":"Human microarray dataset comparing patient-derived SCA3 iPSCs with CRISPR/Cas9-corrected isogenic iPSCs, useful for studying ATXN3 repeat-expansion-dependent transcriptional, apoptosis, and ubiquitin-proteostasis phenotypes.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"CL:0000034","label":"stem cell","display_label":"stem cell","url":"http://purl.obolibrary.org/obo/CL_0000034"}],"sample_type_labels":["stem cell"],"sample_counts":[6],"sample_count":6,"conditions":["SCA3 patient-derived iPSCs","CRISPR/Cas9-corrected isogenic iPSCs"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:34535635"],"publication_contexts":[{"context_id":"disorder:Machado_Joseph_Disease","publication":"PMID:34535635"}],"publication":"PMID:34535635","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34535635","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:34535635","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/34535635","reference_title":"CRISPR/Cas9 mediated gene correction ameliorates abnormal phenotypes in spinocerebellar ataxia type 3 patient-derived induced pluripotent stem cells.","supports":"SUPPORT","evidence_source":null,"snippet":"For the first time, this study demonstrated the feasibility of CRISPR/Cas9-mediated HR strategy to precisely repair SCA3-iPSCs, and reverse the corresponding abnormal disease phenotypes.","explanation":"Supports inclusion of this dataset as a patient-derived isogenic iPSC model resource for SCA3."}],"notes":[],"contexts":[{"id":"disorder:Machado_Joseph_Disease","name":"Machado-Joseph Disease","kind":"Disorder","source_path":"kb/disorders/Machado_Joseph_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Machado_Joseph_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Machado-Joseph_Disease.html#dataset-geo-gse93713"}],"context_names":["Machado-Joseph Disease"],"disease_names":["Machado-Joseph Disease"],"disease_name":"Machado-Joseph Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Machado_Joseph_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Machado_Joseph_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Machado-Joseph_Disease.html#dataset-geo-gse93713"]},{"id":"dataset:geo:gse94462","accession":"geo:GSE94462","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE94462","title":"Comprehensive characterization of DNA methylation changes in Fuchs Endothelial Corneal Dystrophy","alternate_titles":[],"description":"Transparency of the human cornea is necessary for vision. Fuchs Endothelial Corneal Dystrophy (FECD) is a bilateral, heritable degeneration of the corneal endothelium, and a leading indication for corneal transplantation in developed countries. While the early onset, and rarer, form of FECD has been linked to COL8A2 mutations, the more common, late onset form of FECD has genetic mutations linked to only a minority of cases. Epigenetic modifications that occur in FECD are unkonwn. Here, we report on and compare the DNA methyhlation landscape of normal human corneal endothelial (CE) tissue and CE from FECD patients using the Illumina Infinium HumanMethylation450 (HM450) DNA methylation array.","alternate_descriptions":[],"data_types":["METHYLATION"],"data_type_labels":["DNA methylation profiling"],"data_type_label":"DNA methylation profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[16],"sample_count":16,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:31705138"],"publication_contexts":[{"context_id":"disorder:Fuchs_Endothelial_Corneal_Dystrophy","publication":"PMID:31705138"}],"publication":"PMID:31705138","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/31705138","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Fuchs Endothelial Corneal Dystrophy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Fuchs_Endothelial_Corneal_Dystrophy","name":"Fuchs Endothelial Corneal Dystrophy","kind":"Disorder","source_path":"kb/disorders/Fuchs_Endothelial_Corneal_Dystrophy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fuchs_Endothelial_Corneal_Dystrophy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Fuchs_Endothelial_Corneal_Dystrophy.html#dataset-geo-gse94462"}],"context_names":["Fuchs Endothelial Corneal Dystrophy"],"disease_names":["Fuchs Endothelial Corneal Dystrophy"],"disease_name":"Fuchs Endothelial Corneal Dystrophy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Fuchs_Endothelial_Corneal_Dystrophy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fuchs_Endothelial_Corneal_Dystrophy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Fuchs_Endothelial_Corneal_Dystrophy.html#dataset-geo-gse94462"]},{"id":"dataset:geo:gse94535","accession":"geo:GSE94535","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE94535","title":"Circulating plasma microRNA profiling in patients with polymyositis/dermatomyositis before and after treatment","alternate_titles":[],"description":"This study aimed to investigate the expression of microRNAs (miRNAs) in the plasma from polymyositis (PM) and dermatomyositis (DM) patients, which fluctuated by treatment. More differentially expressed miRNAs were found in plasma of DM patients compared to PM patients before and after treatment, and their profiles were different.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[16],"sample_count":16,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:29321815"],"publication_contexts":[{"context_id":"disorder:Polymyositis","publication":"PMID:29321815"}],"publication":"PMID:29321815","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/29321815","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Polymyositis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Polymyositis","name":"Polymyositis","kind":"Disorder","source_path":"kb/disorders/Polymyositis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Polymyositis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Polymyositis.html#dataset-geo-gse94535"}],"context_names":["Polymyositis"],"disease_names":["Polymyositis"],"disease_name":"Polymyositis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Polymyositis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Polymyositis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Polymyositis.html#dataset-geo-gse94535"]},{"id":"dataset:geo:gse94780","accession":"geo:GSE94780","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE94780","title":"Gene expression in rat striatum following carbon monoxide poisoning and hypoxic hypoxia","alternate_titles":[],"description":"We have proposed the existence of a threshold for brain damage, in terms of hydroxyl radical production in rat striatum, between poisoning of carbon monoxide (CO) at 1000 ppm and 3000 ppm, where blood CO-hemoglobin levels reach approximately 50% and over 70%, respectively. To search for factors involved in brain damage, we examined the effects of air, 1000 ppm CO, 3000 ppm CO and 5% O2 (hypoxic conditions comparable with those by 3000 ppm CO) on gene expression in rat striatum, using microarray analysis.","alternate_descriptions":[],"data_types":["MICROARRAY"],"data_type_labels":["Gene expression microarray"],"data_type_label":"Gene expression microarray","organisms":[{"id":"NCBITaxon:10116","label":"Rattus norvegicus","display_label":"rat","url":"http://purl.obolibrary.org/obo/NCBITaxon_10116"}],"organism_labels":["Rattus norvegicus"],"organism_label":"Rattus norvegicus","sample_types":[],"sample_type_labels":[],"sample_counts":[12],"sample_count":12,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Carbon Monoxide Poisoning (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values."],"contexts":[{"id":"disorder:Carbon_Monoxide_Poisoning","name":"Carbon Monoxide Poisoning","kind":"Disorder","source_path":"kb/disorders/Carbon_Monoxide_Poisoning.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Carbon_Monoxide_Poisoning.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Carbon_Monoxide_Poisoning.html#dataset-geo-gse94780"}],"context_names":["Carbon Monoxide Poisoning"],"disease_names":["Carbon Monoxide Poisoning"],"disease_name":"Carbon Monoxide Poisoning","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Carbon_Monoxide_Poisoning.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Carbon_Monoxide_Poisoning.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Carbon_Monoxide_Poisoning.html#dataset-geo-gse94780"]},{"id":"dataset:geo:gse96049","accession":"geo:GSE96049","repository":"GEO","accession_url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE96049","title":"Modeling the mutational and phenotypic landscapes of Pelizaeus-Merzbacher Disease using human iPSC-derived oligodendrocytes","alternate_titles":[],"description":"Pelizaeus-Merzbacher disease (PMD) is a pediatric disease of myelin in the central nervous system and manifests with a wide spectrum of clinical severities. Although PMD is a rare monogenic disease, hundreds of mutations in the X-linked myelin gene proteolipid protein 1 (PLP1) have been identified in humans. Attempts to identify a common pathogenic process underlying PMD have been complicated by an incomplete understanding of PLP1 dysfunction and limited access to primary human oligodendrocytes.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[31],"sample_count":31,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:28366443"],"publication_contexts":[{"context_id":"disorder:Pelizaeus_Merzbacher_Disease","publication":"PMID:28366443"}],"publication":"PMID:28366443","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/28366443","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Identified by GEO DataSets index search for Pelizaeus-Merzbacher Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. 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Figure 6 reports three rats per group; the methods wording is inconsistent, so no unqualified sample_count is assigned. The cell-level pathway scores do not measure autophagic flux. 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Matched because the disease is named in the dataset's own title (\"Influenza\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Influenza","name":"Influenza","kind":"Disorder","source_path":"kb/disorders/Influenza.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Influenza.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Influenza.html#dataset-massive-msv000078740"}],"context_names":["Influenza"],"disease_names":["Influenza"],"disease_name":"Influenza","same_context_model_ids":["model:kb/disorders/Influenza.yaml:Immune-competent microvascularized lung-on-a-chip (IC-LOC) severe H1N1 model"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Influenza.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Influenza.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Influenza.html#dataset-massive-msv000078740"]},{"id":"dataset:massive:msv000078741","accession":"massive:MSV000078741","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000078741","title":"Interactome of the influenza A virus transcription/replication machinery","alternate_titles":[],"description":"Analyses of AP-MS experiments performed in HEK 293T cells infected with the influenza A/WSN/33 virus. In half of the experiments the virus was modified to contain a C-terminal Strep tag on the polymerase subunit PB2. Full details in York et al. 'Interactome analysis of the influenza A virus transcription/replication machinery identifies protein phosphatase 6 as a cellular factor required for efficient virus replication.'","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. 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Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Influenza","name":"Influenza","kind":"Disorder","source_path":"kb/disorders/Influenza.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Influenza.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Influenza.html#dataset-massive-msv000078741"}],"context_names":["Influenza"],"disease_names":["Influenza"],"disease_name":"Influenza","same_context_model_ids":["model:kb/disorders/Influenza.yaml:Immune-competent microvascularized lung-on-a-chip (IC-LOC) severe H1N1 model"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Influenza.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Influenza.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Influenza.html#dataset-massive-msv000078741"]},{"id":"dataset:massive:msv000079017","accession":"massive:MSV000079017","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000079017","title":"Lenalidomide Causes Selective Degradation of IKZF1 and IKZF3 in Multiple Myeloma Cells","alternate_titles":[],"description":"Krönke J, Udeshi ND, Narla A, Grauman P, Hurst SN, McConkey M, Svinkina T, Heckl D, Comer E, Li X, Ciarlo C, Hartman E, Munshi N, Schenone M, Schreiber SL, Carr SA, Ebert BL. Science 2014, 343, 301-305. doi:10.1126/science.1244851. Lenalidomide is a drug with clinical efficacy in multiple myeloma and other B cell neoplasms, but its mechanism of action is unknown. 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Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Huntington_Disease","name":"Huntington Disease","kind":"Disorder","source_path":"kb/disorders/Huntington_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Huntington_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Huntington_Disease.html#dataset-massive-msv000079178"}],"context_names":["Huntington Disease"],"disease_names":["Huntington Disease"],"disease_name":"Huntington Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Huntington_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Huntington_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Huntington_Disease.html#dataset-massive-msv000079178"]},{"id":"dataset:massive:msv000079546","accession":"massive:MSV000079546","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000079546","title":"Proteomic analysis of urinary exosomes in cystinuria patients","alternate_titles":[],"description":"Cystinuria is a rare renal genetic disease caused by mutations in cystine transporter genes and characterized by defective cystine reabsorption leading to kidney stones. In 14% of cases patients undergo nephrectomy, but given the difficulty to predict the evolution of the disease, the identification of markers of kidney damage would improve the follow up of patients with a higher risk. The aim of the present study is to develop a robust, reproducible and non-invasive methodology for proteomic analysis of urinary exosomes using high resolution mass spectrometry.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Cystinuria\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Cystinuria","name":"Cystinuria","kind":"Disorder","source_path":"kb/disorders/Cystinuria.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cystinuria.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cystinuria.html#dataset-massive-msv000079546"}],"context_names":["Cystinuria"],"disease_names":["Cystinuria"],"disease_name":"Cystinuria","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cystinuria.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cystinuria.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cystinuria.html#dataset-massive-msv000079546"]},{"id":"dataset:massive:msv000079572","accession":"massive:MSV000079572","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000079572","title":"Super-SILAC Allows Classification of Diffuse Large B-cell Lymphoma Subtypes by Their Protein Expression Profiles","alternate_titles":[],"description":"Correct classification of cancer patients into subtypes is a prerequisite for acute diagnosis and effective treatment. Currently this classification relies mainly on histological assessment, but gene expression analysis bymicroarrays has shown great promise. Here we show that high accuracy, quantitative proteomics can robustly segregate cancer subtypes directly at the level of expressed proteins.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Diffuse Large B-Cell Lymphoma\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Diffuse_Large_B_Cell_Lymphoma","name":"Diffuse Large B-Cell Lymphoma","kind":"Disorder","source_path":"kb/disorders/Diffuse_Large_B_Cell_Lymphoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Diffuse_Large_B_Cell_Lymphoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Diffuse_Large_B-Cell_Lymphoma.html#dataset-massive-msv000079572"}],"context_names":["Diffuse Large B-Cell Lymphoma"],"disease_names":["Diffuse Large B-Cell Lymphoma"],"disease_name":"Diffuse Large B-Cell Lymphoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Diffuse_Large_B_Cell_Lymphoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Diffuse_Large_B_Cell_Lymphoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Diffuse_Large_B-Cell_Lymphoma.html#dataset-massive-msv000079572"]},{"id":"dataset:massive:msv000079599","accession":"massive:MSV000079599","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000079599","title":"Loss of protein association causes cardiolipin degradation in Barth syndrome","alternate_titles":[],"description":"Loss of protein association causes cardiolipin degradation in Barth syndrome Dataset1: effect of bromopyruvate EH_011316_Forward1.raw (treated: heavy label; control: medium label) EH_011316_Reverse1.raw (treated: medium label; control: heavy label) Dataset2: Barth versus control cell (Barth cells: heavy label; control cells: medium label) EH_020514_mix24H.raw (24 hr incubation, replicate 1) EH_020514_mix32H.raw (32 hr incubation, replicate 1) EH_020614_mix24H.raw (24 hr incubation, replicate 2) EH_020614_mix32H.raw (32 hr incubation, replicate 2) EH_020714_mix24H.raw (24 hr incubation,","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Barth syndrome\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Barth_Syndrome","name":"Barth syndrome","kind":"Disorder","source_path":"kb/disorders/Barth_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Barth_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Barth_syndrome.html#dataset-massive-msv000079599"}],"context_names":["Barth syndrome"],"disease_names":["Barth syndrome"],"disease_name":"Barth syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Barth_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Barth_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Barth_syndrome.html#dataset-massive-msv000079599"]},{"id":"dataset:massive:msv000079600","accession":"massive:MSV000079600","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000079600","title":"Loss of protein association causes cardiolipin degradation in Barth syndrome","alternate_titles":[],"description":"Loss of protein association causes cardiolipin degradation in Barth syndrome","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Barth syndrome\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Barth_Syndrome","name":"Barth syndrome","kind":"Disorder","source_path":"kb/disorders/Barth_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Barth_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Barth_syndrome.html#dataset-massive-msv000079600"}],"context_names":["Barth syndrome"],"disease_names":["Barth syndrome"],"disease_name":"Barth syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Barth_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Barth_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Barth_syndrome.html#dataset-massive-msv000079600"]},{"id":"dataset:massive:msv000079925","accession":"massive:MSV000079925","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000079925","title":"Biomarkers for Cervical Cancer. iTRAQ Discovery.","alternate_titles":[],"description":"We developed a discovery-validation mass-spectrometry based pipeline to identify a set of proteins that are regulated in serum of patients with cervical intraepithelial neoplasia (CIN) and squamous cell cervical cancer using isobaric Tags for Relative and Absolute Quantitation (iTRAQ®), label-free shotgun and targeted mass-spectrometric quantification. At the discovery stage we used a â??poolingâ??","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Cervical Cancer\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Cervical_Cancer","name":"Cervical Cancer","kind":"Disorder","source_path":"kb/disorders/Cervical_Cancer.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cervical_Cancer.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cervical_Cancer.html#dataset-massive-msv000079925"}],"context_names":["Cervical Cancer"],"disease_names":["Cervical Cancer"],"disease_name":"Cervical Cancer","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cervical_Cancer.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cervical_Cancer.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cervical_Cancer.html#dataset-massive-msv000079925"]},{"id":"dataset:massive:msv000079941","accession":"massive:MSV000079941","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000079941","title":"The pathogenesis of Guillain-Barre syndrome: immunological profiling of physiological fluids","alternate_titles":[],"description":"Acute inflammatory demyelinating polyneuropathy (AIDP) - one of the forms of Guillain-Barre syndrome (GBS) - is a rare and severe disorder of the peripheral nervous system that also has an unknown etiology. One of the hallmarks of AIDP pathogenesis is a significantly elevated cerebrospinal fluid (CSF) protein level in comparison with the peptidome/proteome profile of a representative number of CSF samples obtained from AIDP and multiple sclerosis (MS) patients and control patients.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Guillain-Barre Syndrome\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Guillain_Barre_Syndrome","name":"Guillain-Barre Syndrome","kind":"Disorder","source_path":"kb/disorders/Guillain_Barre_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Guillain_Barre_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Guillain-Barre_Syndrome.html#dataset-massive-msv000079941"}],"context_names":["Guillain-Barre Syndrome"],"disease_names":["Guillain-Barre Syndrome"],"disease_name":"Guillain-Barre Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Guillain_Barre_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Guillain_Barre_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Guillain-Barre_Syndrome.html#dataset-massive-msv000079941"]},{"id":"dataset:massive:msv000079963","accession":"massive:MSV000079963","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000079963","title":"The pathogenesis of Guillain-Barre syndrome: peptidomic profiling of physiological fluids","alternate_titles":[],"description":"Acute inflammatory demyelinating polyneuropathy (AIDP) - one of the forms of Guillain-Barre syndrome (GBS) - is a rare and severe disorder of the peripheral nervous system that also has an unknown etiology. One of the hallmarks of AIDP pathogenesis is a significantly elevated cerebrospinal fluid (CSF) protein level in comparison with the peptidome/proteome profile of a representative number of CSF samples obtained from AIDP and multiple sclerosis (MS) patients and control patients.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Guillain-Barre Syndrome\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Guillain_Barre_Syndrome","name":"Guillain-Barre Syndrome","kind":"Disorder","source_path":"kb/disorders/Guillain_Barre_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Guillain_Barre_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Guillain-Barre_Syndrome.html#dataset-massive-msv000079963"}],"context_names":["Guillain-Barre Syndrome"],"disease_names":["Guillain-Barre Syndrome"],"disease_name":"Guillain-Barre Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Guillain_Barre_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Guillain_Barre_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Guillain-Barre_Syndrome.html#dataset-massive-msv000079963"]},{"id":"dataset:massive:msv000079972","accession":"massive:MSV000079972","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000079972","title":"Proteomic analysis of clear cell renal cell carcinoma tissue versus matched normal kidney tissue","alternate_titles":[],"description":"We analyzed 84 tumor/normal pairs (177 total) using standard shotgun proteomic techniques in order to characterize the molecular landscape of clear cell renal cell carcinoma (ccRCC) and interrogated changes in protein abundance and biological pathways with ccRCC grade. These tissues were distributed across stage 1 (n = 34), 2 (n = 40), 3 (n = 42), and 4 (n = 52), with 9 pairs also including samples from metastasized tumor. These data can be (and were) combined with a previously published transcriptomic data set from the same sample cohort (NCBI GEO: GSE53757).","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Clear Cell Renal Cell Carcinoma\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Clear_Cell_Renal_Cell_Carcinoma","name":"Clear Cell Renal Cell Carcinoma","kind":"Disorder","source_path":"kb/disorders/Clear_Cell_Renal_Cell_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Clear_Cell_Renal_Cell_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Clear_Cell_Renal_Cell_Carcinoma.html#dataset-massive-msv000079972"}],"context_names":["Clear Cell Renal Cell Carcinoma"],"disease_names":["Clear Cell Renal Cell Carcinoma"],"disease_name":"Clear Cell Renal Cell Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Clear_Cell_Renal_Cell_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Clear_Cell_Renal_Cell_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Clear_Cell_Renal_Cell_Carcinoma.html#dataset-massive-msv000079972"]},{"id":"dataset:massive:msv000080238","accession":"massive:MSV000080238","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000080238","title":"Mycobacterium tuberculosis normoxia hypoxia reactivation with ActivX-desthiobiotin FP probe","alternate_titles":[],"description":"Lysates of Mycobacterium tuberculosis (H37Rv auxotroph mc(2)6020) grown under various conditions (normoxia, hypoxia, reactivation from hypoxia) probed the serine hydrolase probe with ActivX-desthiobiotin FP.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Tuberculosis\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Tuberculosis","name":"Tuberculosis","kind":"Disorder","source_path":"kb/disorders/Tuberculosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Tuberculosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Tuberculosis.html#dataset-massive-msv000080238"}],"context_names":["Tuberculosis"],"disease_names":["Tuberculosis"],"disease_name":"Tuberculosis","same_context_model_ids":["model:kb/disorders/Tuberculosis.yaml:Autologous iPSC-derived alveolus-on-chip (iLoC) Mtb infection model"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Tuberculosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Tuberculosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Tuberculosis.html#dataset-massive-msv000080238"]},{"id":"dataset:massive:msv000080262","accession":"massive:MSV000080262","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000080262","title":"Proteomic analysis of extracellular vesicles derived from Merkel cell carcinoma cell lines","alternate_titles":[],"description":"Exosomes constitute an evolutionary conserved mechanism of intercellular signaling. Their importance are gaining increasing such as prognostic and diagnostic markers, and potential therapeutic tool. Merkel cell carcinoma (MCC) is an aggressive form of skin cancer with a poor prognosis. There are not available an effective systemic treatment for this type of cancer, and exosome-based therapy was proposed. We identified with high confident 164 exosome-derived proteins that were common for all four cell lines, which were annotated in ExoCarta and Vesiclepedia databases.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Merkel Cell Carcinoma\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Merkel_Cell_Carcinoma","name":"Merkel Cell Carcinoma","kind":"Disorder","source_path":"kb/disorders/Merkel_Cell_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Merkel_Cell_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Merkel_Cell_Carcinoma.html#dataset-massive-msv000080262"}],"context_names":["Merkel Cell Carcinoma"],"disease_names":["Merkel Cell Carcinoma"],"disease_name":"Merkel Cell Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Merkel_Cell_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Merkel_Cell_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Merkel_Cell_Carcinoma.html#dataset-massive-msv000080262"]},{"id":"dataset:massive:msv000080280","accession":"massive:MSV000080280","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000080280","title":"A Protein Deep Sequencing Evaluation of Metastatic Melanoma Tissues, unfractionated approach","alternate_titles":[],"description":"Malignant melanoma has currently the highest increase of incidence of malignancies in the western world. In early stages, front line therapy is surgical excision of the primary tumor. Metastatic disease has previously has very limited possibilities to be cured. Recently, several protein kinase inhibitors and immune modifiers have shown promising results but drug resistance in metastasized melanoma remains a major problem. The need for clinical biomarkers to follow disease progression and treatment effects is high.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Metastatic Melanoma\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Cutaneous_Melanoma","name":"Cutaneous Melanoma","kind":"Disorder","source_path":"kb/disorders/Cutaneous_Melanoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cutaneous_Melanoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cutaneous_Melanoma.html#dataset-massive-msv000080280"}],"context_names":["Cutaneous Melanoma"],"disease_names":["Cutaneous Melanoma"],"disease_name":"Cutaneous Melanoma","same_context_model_ids":["model:kb/disorders/Cutaneous_Melanoma.yaml:Xmrk-activated melanocytes in three-dimensional dermal collagen"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Cutaneous_Melanoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cutaneous_Melanoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cutaneous_Melanoma.html#dataset-massive-msv000080280"]},{"id":"dataset:massive:msv000080282","accession":"massive:MSV000080282","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000080282","title":"A Protein Deep Sequencing Evaluation of Metastatic Melanoma Tissues, fractionated approach","alternate_titles":[],"description":"Malignant melanoma has currently the highest increase of incidence of malignancies in the western world. In early stages, front line therapy is surgical excision of the primary tumor. Metastatic disease has previously has very limited possibilities to be cured. Recently, several protein kinase inhibitors and immune modifiers have shown promising results but drug resistance in metastasized melanoma remains a major problem. The need for clinical biomarkers to follow disease progression and treatment effects is high.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Metastatic Melanoma\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Cutaneous_Melanoma","name":"Cutaneous Melanoma","kind":"Disorder","source_path":"kb/disorders/Cutaneous_Melanoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cutaneous_Melanoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cutaneous_Melanoma.html#dataset-massive-msv000080282"}],"context_names":["Cutaneous Melanoma"],"disease_names":["Cutaneous Melanoma"],"disease_name":"Cutaneous Melanoma","same_context_model_ids":["model:kb/disorders/Cutaneous_Melanoma.yaml:Xmrk-activated melanocytes in three-dimensional dermal collagen"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Cutaneous_Melanoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cutaneous_Melanoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cutaneous_Melanoma.html#dataset-massive-msv000080282"]},{"id":"dataset:massive:msv000080718","accession":"massive:MSV000080718","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000080718","title":"Label-free Proteomic Analysis of Exosomes Derived from Inducible Hepatitis B Virus-Replicating HepAD38 Cell Line","alternate_titles":[],"description":"Hepatitis B virus (HBV) infection is a major health problem worldwide. Recent evidence suggests that various viruses can manipulate the infection process by secretion of specific viral and cellular components into exosomes, small nanometer-sized (30-150 nm) vesicles secreted from various cells. However, the impact of HBV replication on hepatocytes produced exosomes has not been fully delineated. In this work, an HBV-inducible cell line HepAD38 was used to directly compare changes in the protein content of exosomes secreted from HepAD38 cells with or without HBV replication.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Hepatitis B\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Hepatitis_B","name":"Hepatitis B","kind":"Disorder","source_path":"kb/disorders/Hepatitis_B.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatitis_B.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hepatitis_B.html#dataset-massive-msv000080718"}],"context_names":["Hepatitis B"],"disease_names":["Hepatitis B"],"disease_name":"Hepatitis B","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hepatitis_B.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatitis_B.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hepatitis_B.html#dataset-massive-msv000080718"]},{"id":"dataset:massive:msv000080763","accession":"massive:MSV000080763","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000080763","title":"Metaproteomic profiling of saliva in subjects with periodontitis, dental caries and orally healthy controls","alternate_titles":[],"description":"The composition of the salivary microbiota has been reported to differentiate between patients with periodontitis, dental caries and orally healthy individuals. Thus, the purpose of the present investigation was to compare metaproteomic profiles of saliva in oral health and disease. Stimulated saliva samples were collected from 10 patients with periodontitis, 10 patients with dental caries and 10 orally healthy individuals. Samples were analyzed by means of shotgun proteomics. 4161 different proteins were recorded out of which 1946 and 2090 were of bacterial and human origin respectively.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Dental Caries\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Dental_Caries","name":"Dental Caries","kind":"Disorder","source_path":"kb/disorders/Dental_Caries.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dental_Caries.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Dental_Caries.html#dataset-massive-msv000080763"}],"context_names":["Dental Caries"],"disease_names":["Dental Caries"],"disease_name":"Dental Caries","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Dental_Caries.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dental_Caries.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Dental_Caries.html#dataset-massive-msv000080763"]},{"id":"dataset:massive:msv000080779","accession":"massive:MSV000080779","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000080779","title":"Gluten-specific antibodies of celiac disease gut plasma cells recognize long proteolytic fragments that typically harbor T-cell epitopes","alternate_titles":[],"description":"This study aimed to identify proteolytic fragments of gluten proteins recognized by recombinant IgG1 monoclonal antibodies generated from single IgA plasma cells of celiac disease lesions. Peptides bound by monoclonal antibodies in complex gut-enzyme digests of gluten treated with the deamidating enzyme transglutaminase 2, were identified by mass spectrometry after antibody pull-down with protein G beads. The antibody bound peptides were long deamidated peptide fragments that contained the substrate recognition sequence of transglutaminase 2.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Celiac Disease\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Celiac_Disease","name":"Celiac Disease","kind":"Disorder","source_path":"kb/disorders/Celiac_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Celiac_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Celiac_Disease.html#dataset-massive-msv000080779"}],"context_names":["Celiac Disease"],"disease_names":["Celiac Disease"],"disease_name":"Celiac Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Celiac_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Celiac_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Celiac_Disease.html#dataset-massive-msv000080779"]},{"id":"dataset:massive:msv000080781","accession":"massive:MSV000080781","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000080781","title":"HSP90 promotes Burkitt lymphoma cell survival by maintaining tonic B cell receptor signaling","alternate_titles":[],"description":"Burkitt’s lymphoma (BL) is an aggressive B-cell neoplasm that is currently treated by intensive chemotherapy in combination with anti-CD20 antibodies. Because of their toxicity, current treatment regimens are often not suitable for elderly patients or for patients in developing countries where BL is endemic. Hence, there is a need for targeted therapies. In this study, we performed a compound screen in 17 BL cell lines to identify small molecule inhibitors affecting cell survival.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Burkitt Lymphoma\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Burkitt_Lymphoma","name":"Burkitt Lymphoma","kind":"Disorder","source_path":"kb/disorders/Burkitt_Lymphoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Burkitt_Lymphoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Burkitt_Lymphoma.html#dataset-massive-msv000080781"}],"context_names":["Burkitt Lymphoma"],"disease_names":["Burkitt Lymphoma"],"disease_name":"Burkitt Lymphoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Burkitt_Lymphoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Burkitt_Lymphoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Burkitt_Lymphoma.html#dataset-massive-msv000080781"]},{"id":"dataset:massive:msv000080786","accession":"massive:MSV000080786","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000080786","title":"Identification of a biomarker in cerebrospinal fluid for neuronopathic forms of Gaucher disease","alternate_titles":[],"description":"Gaucher disease, a recessive inherited metabolic disorder caused by defects in the gene encoding glucosylceramidase (GlcCerase), can be divided into three subtypes according to the appearance of symptoms associated with central nervous system involvement. We now identify a protein, glycoprotein non-metastatic B (GPNMB), that acts as an authentic marker of brain pathology in neurological forms of Gaucher disease.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Gaucher Disease\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Gaucher_Disease","name":"Gaucher Disease","kind":"Disorder","source_path":"kb/disorders/Gaucher_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Gaucher_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Gaucher_Disease.html#dataset-massive-msv000080786"}],"context_names":["Gaucher Disease"],"disease_names":["Gaucher Disease"],"disease_name":"Gaucher Disease","same_context_model_ids":["model:kb/disorders/Gaucher_Disease.yaml:CBE-treated murine macrophage conditioned-medium model","model:kb/disorders/Gaucher_Disease.yaml:GD1 patient bone marrow stromal cells"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Gaucher_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Gaucher_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Gaucher_Disease.html#dataset-massive-msv000080786"]},{"id":"dataset:massive:msv000080813","accession":"massive:MSV000080813","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000080813","title":"Machine Learning Based Classification of Diffuse Large B-cell Lymphoma Patients by their Protein Expression  Profiles","alternate_titles":[],"description":"Characterization of tumors at the molecular level has improved our knowledge of cancer causation and progression. Proteomic analysis of their signaling pathways promises to enhance our understanding of cancer aberrations at the functional level, but this requires accurate and robust tools. Here, we develop a state of the art quantitative mass spectrometric pipeline to characterize formalin-fixed paraffin-embedded (FFPE) tissues of patients with closely related subtypes of diffuse large B-cell lymphoma (DLBCL).","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Diffuse Large B-Cell Lymphoma\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Diffuse_Large_B_Cell_Lymphoma","name":"Diffuse Large B-Cell Lymphoma","kind":"Disorder","source_path":"kb/disorders/Diffuse_Large_B_Cell_Lymphoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Diffuse_Large_B_Cell_Lymphoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Diffuse_Large_B-Cell_Lymphoma.html#dataset-massive-msv000080813"}],"context_names":["Diffuse Large B-Cell Lymphoma"],"disease_names":["Diffuse Large B-Cell Lymphoma"],"disease_name":"Diffuse Large B-Cell Lymphoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Diffuse_Large_B_Cell_Lymphoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Diffuse_Large_B_Cell_Lymphoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Diffuse_Large_B-Cell_Lymphoma.html#dataset-massive-msv000080813"]},{"id":"dataset:massive:msv000080838","accession":"massive:MSV000080838","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000080838","title":"Comparative shotgun proteomics of aqueous humor for cataract, glaucoma and pseudoexfoliation eye disorders.","alternate_titles":[],"description":"The aim of this work was to characterize proteome of aqueous humor from subjects with various eye conditions such as cataract, glaucoma and pseudoexfoliation syndrome by high-resolution chromate-mass-spectrometry. Twenty nine human aqueous humor samples were processed by shotgun proteomics. Data was searched using MaxQuant package. Totally, 263 protein groups were identified. Label-free quantitation reported some differentially expressed proteins in aqueous humor proteome for the aforementioned eye diseases.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Glaucoma\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Glaucoma","name":"Glaucoma","kind":"Disorder","source_path":"kb/disorders/Glaucoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Glaucoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Glaucoma.html#dataset-massive-msv000080838"}],"context_names":["Glaucoma"],"disease_names":["Glaucoma"],"disease_name":"Glaucoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Glaucoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Glaucoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Glaucoma.html#dataset-massive-msv000080838"]},{"id":"dataset:massive:msv000080855","accession":"massive:MSV000080855","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000080855","title":"Quantitative proteomic study of two cervical cancer cell lines upon re-expression of Galectin 7","alternate_titles":[],"description":"Galectin-7 expression was found to be strongly reduced in cervical cancer cell lines. The same tumor cell lines in which Galectin-7 was ectopically expressed exhibited significant decrease in their tumorigenic capacity in vitro and in vivo. The proteomic changes in the cervical cancer cell lines HeLa and SiHa after Galectin-7 re-expression were here quantified by SILAC.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Cervical Cancer\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Cervical_Cancer","name":"Cervical Cancer","kind":"Disorder","source_path":"kb/disorders/Cervical_Cancer.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cervical_Cancer.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cervical_Cancer.html#dataset-massive-msv000080855"}],"context_names":["Cervical Cancer"],"disease_names":["Cervical Cancer"],"disease_name":"Cervical Cancer","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cervical_Cancer.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cervical_Cancer.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cervical_Cancer.html#dataset-massive-msv000080855"]},{"id":"dataset:massive:msv000080859","accession":"massive:MSV000080859","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000080859","title":"Different Binding Motifs of the Celiac Disease Associated HLA Molecules DQ2.5, DQ2.2 and DQ7.5 Revealed by Relative Quantitative Proteomics of Endogenous Peptide Repertoires","alternate_titles":[],"description":"In this study relative quantitative analysis of endogenous peptides by mass spectrometry combined with neural network analysis have been used to address why the alpha- or beta-chain sharing human leukocyte antigen (HLA)-DQ molecules DQ2.5, DQ2.2 and DQ7.5 display different risks for celiac disease. Celiac disease is caused by intolerance to cereal gluten proteins, and HLA-DQ molecules are involved in the disease pathogenesis by presentation of gluten peptides to CD4+ T cells.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Celiac Disease\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Celiac_Disease","name":"Celiac Disease","kind":"Disorder","source_path":"kb/disorders/Celiac_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Celiac_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Celiac_Disease.html#dataset-massive-msv000080859"}],"context_names":["Celiac Disease"],"disease_names":["Celiac Disease"],"disease_name":"Celiac Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Celiac_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Celiac_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Celiac_Disease.html#dataset-massive-msv000080859"]},{"id":"dataset:massive:msv000080861","accession":"massive:MSV000080861","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000080861","title":"A proteome analysis by LC-MS/MS of human colon mucosal biopsies from gastrointestinal healthy rheumatoid arthritis patients","alternate_titles":[],"description":"The joint disease rheumatoid arthritis (RA) is characterized by persistent synovitis, leading to cartilage damage, bone erosion, and ultimately impaired joint function. The disease affects 0.5 to 1.0% of adults in developed countries, and is three times more frequent in women than in men. A number of autoantibodies can be detected in RA patient’s serum targeting the patient’s own proteins. Several of these proteins, including rheumatoid factor, can also be detected in patients suffering from other autoimmune diseases, including the inflammatory bowel diseases (IBD).","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Rheumatoid Arthritis\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Rheumatoid_Arthritis","name":"Rheumatoid Arthritis","kind":"Disorder","source_path":"kb/disorders/Rheumatoid_Arthritis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rheumatoid_Arthritis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Rheumatoid_Arthritis.html#dataset-massive-msv000080861"}],"context_names":["Rheumatoid Arthritis"],"disease_names":["Rheumatoid Arthritis"],"disease_name":"Rheumatoid Arthritis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Rheumatoid_Arthritis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rheumatoid_Arthritis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Rheumatoid_Arthritis.html#dataset-massive-msv000080861"]},{"id":"dataset:massive:msv000080979","accession":"massive:MSV000080979","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000080979","title":"Cerebrospinal fluid markers to distinguish bacterial meningitis from cerebral malaria in children","alternate_titles":[],"description":"Clinically distinguishing acute bacterial meningitis from cerebral malaria, both of which are important causes of acute non-traumatic coma associated with morbidity and mortality among paediatric hospital admissions in malaria endemic areas of Africa, is challenging. Few hospitals have diagnostic capacity for distinguishing the two syndromes resulting in broader antibiotic cover than necessary. A biochemical marker of ABM would facilitate precise clinical diagnosis and management of these infections.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Bacterial meningitis\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Bacterial_meningitis","name":"Bacterial meningitis","kind":"Disorder","source_path":"kb/disorders/Bacterial_meningitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bacterial_meningitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Bacterial_meningitis.html#dataset-massive-msv000080979"}],"context_names":["Bacterial meningitis"],"disease_names":["Bacterial meningitis"],"disease_name":"Bacterial meningitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Bacterial_meningitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bacterial_meningitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Bacterial_meningitis.html#dataset-massive-msv000080979"]},{"id":"dataset:massive:msv000081061","accession":"massive:MSV000081061","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000081061","title":"De Novo Proteome in Fragile X Syndrome","alternate_titles":[],"description":"Elevated translation has been reported in multiple models of fragile X syndrome (FXS) and in FXS individuals, however, whether it is limited to fragile X mental retardation protein (FMRP) target mRNAs or neuronal activity-derived conditions remains unclear. We examined this question by measuring the de novo proteome of the Fmr1 knockout (KO) mouse hippocampus compared to normal littermates in steady-state and mGluR-stimulated conditions.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Fragile X Syndrome\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Fragile_X_Syndrome","name":"Fragile X Syndrome","kind":"Disorder","source_path":"kb/disorders/Fragile_X_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fragile_X_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Fragile_X_Syndrome.html#dataset-massive-msv000081061"}],"context_names":["Fragile X Syndrome"],"disease_names":["Fragile X Syndrome"],"disease_name":"Fragile X Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Fragile_X_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fragile_X_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Fragile_X_Syndrome.html#dataset-massive-msv000081061"]},{"id":"dataset:massive:msv000081143","accession":"massive:MSV000081143","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000081143","title":"iTRAQ8 analysis of control and neuronal ceroid lipofuscinosis human brain samples.","alternate_titles":[],"description":"iTRAQ8 analysis of autopsy samples representing brain and cerebrospinal fluid from neuronal ceroid lipofuscinosis patients and controls.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Neuronal Ceroid Lipofuscinosis\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Neuronal_Ceroid_Lipofuscinosis","name":"Neuronal Ceroid Lipofuscinosis","kind":"Disorder","source_path":"kb/disorders/Neuronal_Ceroid_Lipofuscinosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Neuronal_Ceroid_Lipofuscinosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Neuronal_Ceroid_Lipofuscinosis.html#dataset-massive-msv000081143"}],"context_names":["Neuronal Ceroid Lipofuscinosis"],"disease_names":["Neuronal Ceroid Lipofuscinosis"],"disease_name":"Neuronal Ceroid Lipofuscinosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Neuronal_Ceroid_Lipofuscinosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Neuronal_Ceroid_Lipofuscinosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Neuronal_Ceroid_Lipofuscinosis.html#dataset-massive-msv000081143"]},{"id":"dataset:massive:msv000081205","accession":"massive:MSV000081205","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000081205","title":"GeLC-MS/MS of H37Rv and two clinical isolates of Mycobacterium tuberculosis","alternate_titles":[],"description":"Clinical isolates were made available from an extensive longitudinal collection of M. tuberculosis isolates circulating in the Western Cape of South Africa. Clinical isolates SAWC3651 and SAWC3517, belonging to the LAM (lineage 4.3) genotype and IS6110 family 14 and 9, respectively, and M. tuberculosis H37Rv were selected for analysis. Proteins were fractionated by SDS-PAGE, using a 4-12% gradient, 1.0 mm NuPage gel (Invitrogen, Carlsbad, CA, USA). Each gel lane was divided into 10 fractions and each fraction was prepared for analysis by mass spectrometry.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Tuberculosis\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Tuberculosis","name":"Tuberculosis","kind":"Disorder","source_path":"kb/disorders/Tuberculosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Tuberculosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Tuberculosis.html#dataset-massive-msv000081205"}],"context_names":["Tuberculosis"],"disease_names":["Tuberculosis"],"disease_name":"Tuberculosis","same_context_model_ids":["model:kb/disorders/Tuberculosis.yaml:Autologous iPSC-derived alveolus-on-chip (iLoC) Mtb infection model"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Tuberculosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Tuberculosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Tuberculosis.html#dataset-massive-msv000081205"]},{"id":"dataset:massive:msv000081625","accession":"massive:MSV000081625","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000081625","title":"Proteome of Gastrointestinal Stromal Tumor-Derived Exosomes","alternate_titles":[],"description":"Proteomic study of GIST-derived exosomes (GDEs) and identified 1,060 proteins composing the core GDE proteome (cGDEp). The cGDEp was enriched in diagnostic markers (e.g., KIT, CD34, ANO1, PROM1, PRKCQ, and ENG), as well as proteins encoded by genes previously reported expressed in GIST (e.g., DPP4, FHL1, CDH11, and KCTD12). Many of these proteins were validated using cell lines, patient-derived KIT+ exosomes, and GIST tissues.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Gastrointestinal Stromal Tumor\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Gastrointestinal_Stromal_Tumor","name":"Gastrointestinal Stromal Tumor","kind":"Disorder","source_path":"kb/disorders/Gastrointestinal_Stromal_Tumor.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Gastrointestinal_Stromal_Tumor.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Gastrointestinal_Stromal_Tumor.html#dataset-massive-msv000081625"}],"context_names":["Gastrointestinal Stromal Tumor"],"disease_names":["Gastrointestinal Stromal Tumor"],"disease_name":"Gastrointestinal Stromal Tumor","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Gastrointestinal_Stromal_Tumor.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Gastrointestinal_Stromal_Tumor.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Gastrointestinal_Stromal_Tumor.html#dataset-massive-msv000081625"]},{"id":"dataset:massive:msv000081702","accession":"massive:MSV000081702","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000081702","title":"Differential Proteomic Analysis of Bordetella pertussis OMV","alternate_titles":[],"description":"Differential proteomic analysis of outer membrane vesicles from Bordetella pertussis (two strains: Bvg+ and Bvg-)","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Pertussis\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Pertussis","name":"Pertussis","kind":"Disorder","source_path":"kb/disorders/Pertussis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pertussis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pertussis.html#dataset-massive-msv000081702"}],"context_names":["Pertussis"],"disease_names":["Pertussis"],"disease_name":"Pertussis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Pertussis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pertussis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Pertussis.html#dataset-massive-msv000081702"]},{"id":"dataset:massive:msv000081757","accession":"massive:MSV000081757","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000081757","title":"Retinal proteomic profiling in the course of experimental glaucoma","alternate_titles":[],"description":"Intraocular pressure was elevated through episkleral vein occlusion by thermic cauterization of SD rats. Animals were further sacrificed after different periods of elevated IOP and the retinal proteins were investigated for alterations regarding the relative protein level in this experimental model of glaucoma.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Glaucoma\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Glaucoma","name":"Glaucoma","kind":"Disorder","source_path":"kb/disorders/Glaucoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Glaucoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Glaucoma.html#dataset-massive-msv000081757"}],"context_names":["Glaucoma"],"disease_names":["Glaucoma"],"disease_name":"Glaucoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Glaucoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Glaucoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Glaucoma.html#dataset-massive-msv000081757"]},{"id":"dataset:massive:msv000082644","accession":"massive:MSV000082644","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000082644","title":"Proteomics, post-translational modifications, and integrative analyses reveal heterogeneity of molecular mechanisms within medulloblastoma subgroups","alternate_titles":[],"description":"Archer TC, Ehrenberger T, Mundt F, Gold MP, Krug K, Mah CK, Mahoney EL, Daniel CJ, LeNail A, Ramamoorthy D, Mertins P, Mani DR, Zhang H, Gillette MA, Clauser K, Noble M, Tang LC, Francois JP, Silterra J, Jensen J, Tamayo P, Korshunov A, Pfister SM, Kool M, Northcott PA, Sears RC, Lipton JO, Carr SA, Mesirov JP, Pomeroy SL, Fraenkel E. Cancer Cell 2018. There is a pressing need to identify therapeutic targets in tumors with low mutation rates such as the malignant pediatric brain tumor medulloblastoma.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Medulloblastoma\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Medulloblastoma","name":"Medulloblastoma","kind":"Disorder","source_path":"kb/disorders/Medulloblastoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Medulloblastoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Medulloblastoma.html#dataset-massive-msv000082644"}],"context_names":["Medulloblastoma"],"disease_names":["Medulloblastoma"],"disease_name":"Medulloblastoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Medulloblastoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Medulloblastoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Medulloblastoma.html#dataset-massive-msv000082644"]},{"id":"dataset:massive:msv000082825","accession":"massive:MSV000082825","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000082825","title":"Immunoregulatory Effects of Myeloid-Derived Suppressor Cell Exosomes in Mouse Model of Autoimmune Alopecia Areata","alternate_titles":[],"description":"We have demonstrated therapeutic efficacy of MDSC in mouse Alopecia Areata (AA). In the same AA model, we now asked whether MDSC exosomes (MDSC-Exo) can replace MDSC. MDSC-Exo from bone marrow cells (BMC) cultures of healthy donors could substantially facilitate treatment. With knowledge on MDSC-Exo being limited, their suitability needs to be verified in advance. Protein marker profiles suggest comparability of BMC- to ex vivo collected inflammatory MDSC/MDSC-Exo in mice with a chronic contact dermatitis, which is a therapeutic option in AA.","alternate_descriptions":[],"data_types":["PROTEOMICS"],"data_type_labels":["Protein expression profiling"],"data_type_label":"Protein expression profiling","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Alopecia Areata\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Alopecia_Areata","name":"Alopecia Areata","kind":"Disorder","source_path":"kb/disorders/Alopecia_Areata.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alopecia_Areata.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Alopecia_Areata.html#dataset-massive-msv000082825"}],"context_names":["Alopecia Areata"],"disease_names":["Alopecia Areata"],"disease_name":"Alopecia Areata","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Alopecia_Areata.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alopecia_Areata.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Alopecia_Areata.html#dataset-massive-msv000082825"]},{"id":"dataset:massive:msv000082828","accession":"massive:MSV000082828","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000082828","title":"Proteomic Manifestations of Genetic Defects in Autosomal Recessive Congenital Ichthyosis","alternate_titles":[],"description":"Numerous genetic conditions give rise to a scaly skin phenotype as a result of impaired barrier function. Differences in appearance suggest the response of epidermal cells depends upon the basic defect. The present work characterizes the departure of afflicted corneocytes from normal as judged by their proteomic profiles in three types of autosomal recessive congenital ichthyosis arising from defects in the genes PNPLA1, SDR9C7 and TGM1. The results show that the profiles were distinctive, each displaying a set of altered protein levels, but with a subset of common alterations.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Autosomal Recessive Congenital Ichthyosis\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Autosomal_Recessive_Congenital_Ichthyosis","name":"Autosomal Recessive Congenital Ichthyosis","kind":"Disorder","source_path":"kb/disorders/Autosomal_Recessive_Congenital_Ichthyosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autosomal_Recessive_Congenital_Ichthyosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Recessive_Congenital_Ichthyosis.html#dataset-massive-msv000082828"}],"context_names":["Autosomal Recessive Congenital Ichthyosis"],"disease_names":["Autosomal Recessive Congenital Ichthyosis"],"disease_name":"Autosomal Recessive Congenital Ichthyosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Autosomal_Recessive_Congenital_Ichthyosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autosomal_Recessive_Congenital_Ichthyosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Autosomal_Recessive_Congenital_Ichthyosis.html#dataset-massive-msv000082828"]},{"id":"dataset:massive:msv000082883","accession":"massive:MSV000082883","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000082883","title":"Chronic pancreatitis vs pancreatic cancer LC-MS","alternate_titles":[],"description":"Age-standardized incidence rates for pancreatic cancer (PC) in men have increased by 25% from 1957 to 2011 in Finland. The average age of diagnosis for PC is 69 years in Nordic males, whereas the average age of diagnosis of chronic pancreatitis (CP) is 40-50 years, but the cases overlap in age. By radiology the evaluation of a pancreatic mass, i.e. the differential diagnosis between CP and PC is often difficult. Preoperative needle biopsies are difficult to obtain and are demanding to interpret. New blood based biomarkers are needed.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Chronic Pancreatitis\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Chronic_Pancreatitis","name":"Chronic Pancreatitis","kind":"Disorder","source_path":"kb/disorders/Chronic_Pancreatitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Pancreatitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chronic_Pancreatitis.html#dataset-massive-msv000082883"}],"context_names":["Chronic Pancreatitis"],"disease_names":["Chronic Pancreatitis"],"disease_name":"Chronic Pancreatitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chronic_Pancreatitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Pancreatitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chronic_Pancreatitis.html#dataset-massive-msv000082883"]},{"id":"dataset:massive:msv000082884","accession":"massive:MSV000082884","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000082884","title":"Quantitative proteomic analysis of gallbladder cancer","alternate_titles":[],"description":"We carried out an iTRAQ-based quantitative proteomic analysis of gallbladder cancer and adjacent non-tumor tissue to systematically identify differentially expressed proteins in gallbladder cancer. Ten gallbladder adenocarcinoma and ten adjacent non-tumor tissue samples were selected post pathological confirmation for the study. Samples were pooled and In-solution trypsin digestion was carried out. Post digestion, peptides were iTRAQ labeled with 114 and 115 (gallbladder adenocarcinoma) and 116 and 117 (adjacent non-tumor samples).","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Gallbladder Cancer\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Gallbladder_Cancer","name":"Gallbladder Cancer","kind":"Disorder","source_path":"kb/disorders/Gallbladder_Cancer.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Gallbladder_Cancer.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Gallbladder_Cancer.html#dataset-massive-msv000082884"}],"context_names":["Gallbladder Cancer"],"disease_names":["Gallbladder Cancer"],"disease_name":"Gallbladder Cancer","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Gallbladder_Cancer.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Gallbladder_Cancer.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Gallbladder_Cancer.html#dataset-massive-msv000082884"]},{"id":"dataset:massive:msv000082941","accession":"massive:MSV000082941","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000082941","title":"Aging-related proteome alterations in B cells may predispose for chronic lymphocytic leukemia - nuclear proteins of elderly B cells","alternate_titles":[],"description":"Chronic lymphocytic leukemia (CLL), the most common type of leukemia in adults, is still incurable despite the development of novel therapeutic strategies. This reflects the incomplete understanding of the pathophysiology of this disease. In order to get more detailed insights into CLL development, we performed a comprehensive proteome analysis of primary human CLL cells and B cells from young and age-matched healthy individuals. For comparison, we also analyzed the chronic B cell leukemia cell line JVM-13 showing rather limited similarity to the primary cells.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Chronic Lymphocytic Leukemia\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Chronic_Lymphocytic_Leukemia","name":"Chronic Lymphocytic Leukemia","kind":"Disorder","source_path":"kb/disorders/Chronic_Lymphocytic_Leukemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Lymphocytic_Leukemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chronic_Lymphocytic_Leukemia.html#dataset-massive-msv000082941"}],"context_names":["Chronic Lymphocytic Leukemia"],"disease_names":["Chronic Lymphocytic Leukemia"],"disease_name":"Chronic Lymphocytic Leukemia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chronic_Lymphocytic_Leukemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Lymphocytic_Leukemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chronic_Lymphocytic_Leukemia.html#dataset-massive-msv000082941"]},{"id":"dataset:massive:msv000082954","accession":"massive:MSV000082954","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000082954","title":"STAG2 Loss Rewires Oncogenic and Developmental Programs to Promote Metastasis in Ewing Sarcoma","alternate_titles":[],"description":"Adane B, Alexe G, Seong BKA, Lu D, Hwang E, Hnisz D, Lareau CA, Ross L, Lin S, Dela Cruz FS, Richardson M, Weintraub AS, Wang S, Balboni-Iniguez A, Dharia NV, Conway AS, Robichaud AL, Tanenbaum B, Krill-Burger JM, Vazquez F, Schenone M, Berman JN, Kung A, Carr SA, Aryee MJ, Young RA, Crompton BD, Stegmaier K. 2021 Cancer Cell. The core cohesin subunit STAG2 is recurrently mutated in Ewing sarcoma but its biological role is less clear. Herein, we demonstrate that cohesin complexes containing STAG2 occupy enhancer and polycomb repressive complex (PRC2) marked regulatory regions.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Ewing Sarcoma\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Ewing_Sarcoma","name":"Ewing Sarcoma","kind":"Disorder","source_path":"kb/disorders/Ewing_Sarcoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ewing_Sarcoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#dataset-massive-msv000082954"}],"context_names":["Ewing Sarcoma"],"disease_names":["Ewing Sarcoma"],"disease_name":"Ewing Sarcoma","same_context_model_ids":["model:kb/disorders/Ewing_Sarcoma.yaml:BARD1-variant PSaRC318 and BARD1-depleted Ewing cells","model:kb/disorders/Ewing_Sarcoma.yaml:Ewing sarcoma tumor organoid model systems","model:kb/disorders/Ewing_Sarcoma.yaml:Flow-perfusion Ewing sarcoma 3D scaffold coculture","model:kb/disorders/Ewing_Sarcoma.yaml:Human embryonic mesenchymal stem cell EWS-FLI1 transformation model","model:kb/disorders/Ewing_Sarcoma.yaml:Patient-derived Ewing sarcoma culture panel"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Ewing_Sarcoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ewing_Sarcoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Ewing_Sarcoma.html#dataset-massive-msv000082954"]},{"id":"dataset:massive:msv000083564","accession":"massive:MSV000083564","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000083564","title":"Structural, molecular and cellular impact of the Ogden syndrome mutant N-terminal acetyltransferase hNaa10-Ser37Pro","alternate_titles":[],"description":"Abstract still has to be written. The obtained peptide mixtures were introduced into an LC-MS/MS system, the Ultimate 3000 (Dionex, Amsterdam, The Netherlands) in-line connected to an LTQ Orbitrap XL mass spectrometer (Thermo Fisher Scientific, Bremen, Germany). Samples were first loaded on a trapping column (made in-house, 100 um internal diameter (I.D.) x 20 mm, 5 um beads C18 Reprosil-HD, Dr. Maisch). After back-flushing from the trapping column, the sample was loaded on a reverse-phase column (made in-house, 75 um I.D. x 150 mm, 5 um beads C18 Reprosil-HD, Dr. Maisch).","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Ogden syndrome\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Ogden_syndrome","name":"Ogden syndrome","kind":"Disorder","source_path":"kb/disorders/Ogden_syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ogden_syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Ogden_syndrome.html#dataset-massive-msv000083564"}],"context_names":["Ogden syndrome"],"disease_names":["Ogden syndrome"],"disease_name":"Ogden syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Ogden_syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Ogden_syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Ogden_syndrome.html#dataset-massive-msv000083564"]},{"id":"dataset:massive:msv000084199","accession":"massive:MSV000084199","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000084199","title":"Composition of the Intranuclear Inclusions of Fragile X-associated Tremor/Ataxia Syndrome","alternate_titles":[],"description":"Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder associated with a premutation repeat expansion (55-200 CGG repeats) in the 5 prime noncoding region of the FMR1 gene. Solitary intranuclear inclusions within FXTAS neurons and astrocytes constitute a hallmark of the disorder, yet our understanding of how and why these bodies form is limited.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"fragile X-associated tremor/ataxia syndrome\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Fragile_X-Associated_Tremor_Ataxia_Syndrome","name":"Fragile X-Associated Tremor Ataxia Syndrome","kind":"Disorder","source_path":"kb/disorders/Fragile_X-Associated_Tremor_Ataxia_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fragile_X-Associated_Tremor_Ataxia_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Fragile_X-Associated_Tremor_Ataxia_Syndrome.html#dataset-massive-msv000084199"}],"context_names":["Fragile X-Associated Tremor Ataxia Syndrome"],"disease_names":["Fragile X-Associated Tremor Ataxia Syndrome"],"disease_name":"Fragile X-Associated Tremor Ataxia Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Fragile_X-Associated_Tremor_Ataxia_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fragile_X-Associated_Tremor_Ataxia_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Fragile_X-Associated_Tremor_Ataxia_Syndrome.html#dataset-massive-msv000084199"]},{"id":"dataset:massive:msv000084273","accession":"massive:MSV000084273","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000084273","title":"TWEAK/Fn14 signalling promotes cholangiocarcinoma niche formation and progression","alternate_titles":[],"description":"Cholangiocarcinoma is a cancer of the hepatic bile ducts that is typically detected at a stage too advanced for resection. Additionally, chemotherapy is of limited efficacy, hence, novel therapeutic approaches are urgently required, including targeting of the cancer stroma. A macrophage-derived signal, tumour necrosis factor-like weak inducer of apoptosis (TWEAK), binds to cell-surface fibroblast growth factor-inducible 14 (Fn14), on cholangiocarcinoma cells to induce cytokine and chemokine expression and secretion.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Cholangiocarcinoma\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Cholangiocarcinoma","name":"Cholangiocarcinoma","kind":"Disorder","source_path":"kb/disorders/Cholangiocarcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cholangiocarcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cholangiocarcinoma.html#dataset-massive-msv000084273"}],"context_names":["Cholangiocarcinoma"],"disease_names":["Cholangiocarcinoma"],"disease_name":"Cholangiocarcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cholangiocarcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cholangiocarcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cholangiocarcinoma.html#dataset-massive-msv000084273"]},{"id":"dataset:massive:msv000084800","accession":"massive:MSV000084800","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000084800","title":"Ubiquitin Proteomics Analysis of Systemic Sclerosis Lung Fibroblasts with or without KLHL42 knockdown","alternate_titles":[],"description":"Systemic scleroderma (SSc) is an autoimmune disease which results in fibrotic production in the lung. Resultant SSC-pulmonary fibrosis is the main cause of mortality among SSc patients. From high throughput RNAi screening, we uncovered the ubiquitin E3 ligase KLHL42 as a potential pro-fibrotic mediator of TGFb-dependent fibrotic signaling in primary SSc lung fibroblasts. In this analysis, we sought to uncover putative substrates for KLHL42 by comparing SSc lung fibroblasts with control or KLHL42 siRNA prior to TGFb-treatment, lysis, and TUBE precipitation.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Systemic Sclerosis\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Systemic_Sclerosis","name":"Systemic Sclerosis","kind":"Disorder","source_path":"kb/disorders/Systemic_Sclerosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Systemic_Sclerosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Systemic_Sclerosis.html#dataset-massive-msv000084800"}],"context_names":["Systemic Sclerosis"],"disease_names":["Systemic Sclerosis"],"disease_name":"Systemic Sclerosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Systemic_Sclerosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Systemic_Sclerosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Systemic_Sclerosis.html#dataset-massive-msv000084800"]},{"id":"dataset:massive:msv000084862","accession":"massive:MSV000084862","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000084862","title":"Proteogenomics of High hyperdiploid childhood acute lymphoblastic leukemia","alternate_titles":[],"description":"Proteogenomic analysis and genomic profiling, RNA-sequencing, and mass spectrometry-based analysis of High hyperdiploid childhood acute lymphoblastic leukemia.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Acute Lymphoblastic Leukemia\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Acute_Lymphoblastic_Leukemia","name":"Acute Lymphoblastic Leukemia","kind":"Disorder","source_path":"kb/disorders/Acute_Lymphoblastic_Leukemia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Acute_Lymphoblastic_Leukemia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Acute_Lymphoblastic_Leukemia.html#dataset-massive-msv000084862"}],"context_names":["Acute Lymphoblastic Leukemia"],"disease_names":["Acute Lymphoblastic Leukemia"],"disease_name":"Acute Lymphoblastic Leukemia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Acute_Lymphoblastic_Leukemia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Acute_Lymphoblastic_Leukemia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Acute_Lymphoblastic_Leukemia.html#dataset-massive-msv000084862"]},{"id":"dataset:massive:msv000085040","accession":"massive:MSV000085040","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000085040","title":"Effect of senolytics (Navitoclax, ABT263) on recovery following Myocardial Infarction","alternate_titles":[],"description":"Ischemia reperfusion injury (IRI) following intervention for myocardial infarction remains an unmet clinical problem. Using an established mouse model, we demonstrated that IRI induces multiple cardiac cell linages to senescence. Senescence is is detrimental to recovery, as treatment with the senolytic navitoclax improves functional recovery.Here we are using SWATH-MS to investigate the molecular mechanisms responsible for the effect of navitoclax treatment.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Myocardial Infarction\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Myocardial_Infarction","name":"Myocardial Infarction","kind":"Disorder","source_path":"kb/disorders/Myocardial_Infarction.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myocardial_Infarction.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Myocardial_Infarction.html#dataset-massive-msv000085040"}],"context_names":["Myocardial Infarction"],"disease_names":["Myocardial Infarction"],"disease_name":"Myocardial Infarction","same_context_model_ids":["model:kb/disorders/Myocardial_Infarction.yaml:Bioelectronically instrumented heart-on-a-chip under acute hypoxia","model:kb/disorders/Myocardial_Infarction.yaml:Epicardial-myocardial heart-on-a-chip model of ischemia-reperfusion injury","model:kb/disorders/Myocardial_Infarction.yaml:Human cardiac infarct organoid with an internal oxygen-diffusion gradient","model:kb/disorders/Myocardial_Infarction.yaml:Human heart-on-a-chip ischemia-reperfusion assay with endothelial extracellular vesicle rescue","model:kb/disorders/Myocardial_Infarction.yaml:Myocardial infarct border-zone-on-a-chip"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Myocardial_Infarction.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Myocardial_Infarction.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Myocardial_Infarction.html#dataset-massive-msv000085040"]},{"id":"dataset:massive:msv000085232","accession":"massive:MSV000085232","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000085232","title":"Metaproteomics investigation on the gut microbiota of children affected by Autism Spectrum Disorder","alternate_titles":[],"description":"Metaproteomics investigation of the Gut Microbiota in young subjects with Autism Spectrum Disorders and their relatives","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Autism Spectrum Disorder\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Autism_Spectrum_Disorder","name":"Autism Spectrum Disorder","kind":"Disorder","source_path":"kb/disorders/Autism_Spectrum_Disorder.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autism_Spectrum_Disorder.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Autism_Spectrum_Disorder.html#dataset-massive-msv000085232"}],"context_names":["Autism Spectrum Disorder"],"disease_names":["Autism Spectrum Disorder"],"disease_name":"Autism Spectrum Disorder","same_context_model_ids":["model:kb/disorders/Autism_Spectrum_Disorder.yaml:Genotype-defined patient iPSC-derived neuronal networks","model:kb/disorders/Autism_Spectrum_Disorder.yaml:Multi-genotype human cortical organoid and neural-progenitor panel"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Autism_Spectrum_Disorder.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Autism_Spectrum_Disorder.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Autism_Spectrum_Disorder.html#dataset-massive-msv000085232"]},{"id":"dataset:massive:msv000085234","accession":"massive:MSV000085234","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000085234","title":"Proteomics of plasma exosomes in human cystic echinococcosis","alternate_titles":[],"description":"Exosomes represent an important way of cell-cell communication. Their release into the bloodstream is similar to sending bottle messages that can safely reach (distant) target tissues and cells. In disease contexts, these vesicles provide a suitable source of markers of pathogenesis or carcinogenesis, as well as of the immune response and the host-pathogens interplay. In cystic echinococcosis (CE), the availability of a marker-based blood test would represent an extraordinary advantage for disease diagnosis, staging and follow-up.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Cystic echinococcosis\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Cystic_Echinococcosis","name":"Cystic echinococcosis","kind":"Disorder","source_path":"kb/disorders/Cystic_Echinococcosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cystic_Echinococcosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cystic_echinococcosis.html#dataset-massive-msv000085234"}],"context_names":["Cystic echinococcosis"],"disease_names":["Cystic echinococcosis"],"disease_name":"Cystic echinococcosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cystic_Echinococcosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cystic_Echinococcosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cystic_echinococcosis.html#dataset-massive-msv000085234"]},{"id":"dataset:massive:msv000085361","accession":"massive:MSV000085361","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000085361","title":"Molecular Signatures of Preeclampsia and Gestational Diabetes Mellitus Utilizing Multi-Omics Analyses, Part 2","alternate_titles":[],"description":"The application of multi-omic evaluations, multi-dimensional analysis methods, and new cheminformatics-based visualization tools to provide an in depth understanding of the molecular changes taking place in preeclampsia (PRE) and gestational diabetes mellitus (GDM) patients. Since PRE and GDM are two prevalent pregnancy complications that result in adverse health effects for both the mother and fetus during pregnancy and later in life, a better understanding of each is essential.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Preeclampsia\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Preeclampsia","name":"Preeclampsia","kind":"Disorder","source_path":"kb/disorders/Preeclampsia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Preeclampsia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Preeclampsia.html#dataset-massive-msv000085361"}],"context_names":["Preeclampsia"],"disease_names":["Preeclampsia"],"disease_name":"Preeclampsia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Preeclampsia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Preeclampsia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Preeclampsia.html#dataset-massive-msv000085361"]},{"id":"dataset:massive:msv000085477","accession":"massive:MSV000085477","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000085477","title":"Characterization of the Cerebrospinal Fluid Proteome in Patients with Fragile X-Associated Tremor/Ataxia Syndrome","alternate_titles":[],"description":"Quantitative proteomics analysis of FXTAS patient CSF compared to age-matched controls using iTRAQ labeling","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"fragile X-associated tremor/ataxia syndrome\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Fragile_X-Associated_Tremor_Ataxia_Syndrome","name":"Fragile X-Associated Tremor Ataxia Syndrome","kind":"Disorder","source_path":"kb/disorders/Fragile_X-Associated_Tremor_Ataxia_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fragile_X-Associated_Tremor_Ataxia_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Fragile_X-Associated_Tremor_Ataxia_Syndrome.html#dataset-massive-msv000085477"}],"context_names":["Fragile X-Associated Tremor Ataxia Syndrome"],"disease_names":["Fragile X-Associated Tremor Ataxia Syndrome"],"disease_name":"Fragile X-Associated Tremor Ataxia Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Fragile_X-Associated_Tremor_Ataxia_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fragile_X-Associated_Tremor_Ataxia_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Fragile_X-Associated_Tremor_Ataxia_Syndrome.html#dataset-massive-msv000085477"]},{"id":"dataset:massive:msv000085703","accession":"massive:MSV000085703","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000085703","title":"Large-scale Multi-omic Analysis of COVID-19 Severity","alternate_titles":[],"description":"We performed RNA-Seq and high-resolution mass spectrometry on 128 blood samples from COVID-19 positive and negative patients with diverse disease severities. Over 17,000 transcripts, proteins, metabolites, and lipids were quantified and associated with clinical outcomes in a curated relational database, uniquely enabling systems analysis and cross-ome correlations to molecules and patient prognoses. We mapped 219 molecular features with high significance to COVID-19 status and severity, many involved in complement activation, dysregulated lipid transport, and neutrophil activation.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"COVID-19\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:COVID-19","name":"COVID-19","kind":"Disorder","source_path":"kb/disorders/COVID-19.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/COVID-19.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/COVID-19.html#dataset-massive-msv000085703"}],"context_names":["COVID-19"],"disease_names":["COVID-19"],"disease_name":"COVID-19","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/COVID-19.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/COVID-19.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/COVID-19.html#dataset-massive-msv000085703"]},{"id":"dataset:massive:msv000086005","accession":"massive:MSV000086005","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000086005","title":"Monocytes Release Endogenous Retroviral Protein in Exosomes Causing  a Mesenchymal, Proinflammatory Endothelium  and Pulmonary Hypertension","alternate_titles":[],"description":"Human endogenous retroviral (HERV) proteins are induced by exogenous viruses or other factors that derepress HERV transcription and translation. Previously we showed that HERV-K envelope and deoxyuridine triphosphate nucleotidohydrolase (dUTPase) proteins are increased in monocytes and macrophages from patients with pulmonary arterial hypertension (PAH). Recombinant HERV-K dUTPase upregulates IL6 in pulmonary arterial endothelial cells (PAECs) and induces pulmonary hypertension in rats.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Pulmonary hypertension\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Pulmonary_hypertension","name":"Pulmonary_hypertension","kind":"Disorder","source_path":"kb/disorders/Pulmonary_hypertension.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pulmonary_hypertension.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pulmonary_hypertension.html#dataset-massive-msv000086005"}],"context_names":["Pulmonary_hypertension"],"disease_names":["Pulmonary_hypertension"],"disease_name":"Pulmonary_hypertension","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Pulmonary_hypertension.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pulmonary_hypertension.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Pulmonary_hypertension.html#dataset-massive-msv000086005"]},{"id":"dataset:massive:msv000086108","accession":"massive:MSV000086108","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000086108","title":"Influenza vaccination in the elderly boosts antibodies against conserved viral proteins and egg-produced glycans","alternate_titles":[],"description":"Proteomic analysis of serum IgG antibody repertoire against influenza vaccine H1 (H1N1 A/California/7/2009) and H3 (H3N2 A/Texas/50/2012) in young, middle-aged, and elderly donors vaccinated with Fluzone 2013-14/14-15. Dataset consists of peak-response (days 21-28 post-vaccination) serum IgG samples eluted by affinity chromatography against H1 and H3 vaccine or hemagglutinin and the flow-throughs.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Influenza\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Influenza","name":"Influenza","kind":"Disorder","source_path":"kb/disorders/Influenza.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Influenza.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Influenza.html#dataset-massive-msv000086108"}],"context_names":["Influenza"],"disease_names":["Influenza"],"disease_name":"Influenza","same_context_model_ids":["model:kb/disorders/Influenza.yaml:Immune-competent microvascularized lung-on-a-chip (IC-LOC) severe H1N1 model"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Influenza.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Influenza.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Influenza.html#dataset-massive-msv000086108"]},{"id":"dataset:massive:msv000086114","accession":"massive:MSV000086114","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000086114","title":"Proteomic study in Pompe disease","alternate_titles":[],"description":"The raw data of SWATH proteomic analysis of plasma in Pompe disease patients and controls","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Pompe Disease\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Pompe_Disease","name":"Pompe Disease","kind":"Disorder","source_path":"kb/disorders/Pompe_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pompe_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pompe_Disease.html#dataset-massive-msv000086114"}],"context_names":["Pompe Disease"],"disease_names":["Pompe Disease"],"disease_name":"Pompe Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Pompe_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pompe_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Pompe_Disease.html#dataset-massive-msv000086114"]},{"id":"dataset:massive:msv000086400","accession":"massive:MSV000086400","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000086400","title":"Human cerebral cortex proteome of fragile X-associated tremor/ataxia syndrome","alternate_titles":[],"description":"Background: Fragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder associated with premutation CGG-repeat expansions (55-200 repeats) in the 5 prime non-coding portion of the FMR1 gene. Core features of FXTAS include progressive tremor/ataxia, cognitive decline, variable brain volume loss, and white matter disease. The principal histopathological feature of FXTAS is the presence of CNS and non-CNS intranuclear inclusions. Objective: To further elucidate the molecular underpinnings of FXTAS through the proteomic characterization of human FXTAS cortexes.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"fragile X-associated tremor/ataxia syndrome\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Fragile_X-Associated_Tremor_Ataxia_Syndrome","name":"Fragile X-Associated Tremor Ataxia Syndrome","kind":"Disorder","source_path":"kb/disorders/Fragile_X-Associated_Tremor_Ataxia_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fragile_X-Associated_Tremor_Ataxia_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Fragile_X-Associated_Tremor_Ataxia_Syndrome.html#dataset-massive-msv000086400"}],"context_names":["Fragile X-Associated Tremor Ataxia Syndrome"],"disease_names":["Fragile X-Associated Tremor Ataxia Syndrome"],"disease_name":"Fragile X-Associated Tremor Ataxia Syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Fragile_X-Associated_Tremor_Ataxia_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fragile_X-Associated_Tremor_Ataxia_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Fragile_X-Associated_Tremor_Ataxia_Syndrome.html#dataset-massive-msv000086400"]},{"id":"dataset:massive:msv000086425","accession":"massive:MSV000086425","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000086425","title":"Dysregulation of the complement and coagulation cascade in treated schizophrenia and bipolar disorder patients","alternate_titles":[],"description":"A better understanding of the proteomic profile after bipolar disorder (BD) and schizophrenia (SCZ) treatment, through monitoring its progression, may assist the development of novel therapeutic strategies with the ability to reduce or control possible side effects. In this study, proteomics analysis employing liquid chromatography coupled to mass spectrometry (LC-MS) and bioinformatic tools were applied to identify differentially expressed proteins in serum of treated BD and SCZ patients. In total, 10 BD patients, 10 SCZ patients, and 14 healthy participants were included.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Bipolar Disorder\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Bipolar_Disorder","name":"Bipolar Disorder","kind":"Disorder","source_path":"kb/disorders/Bipolar_Disorder.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bipolar_Disorder.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Bipolar_Disorder.html#dataset-massive-msv000086425"}],"context_names":["Bipolar Disorder"],"disease_names":["Bipolar Disorder"],"disease_name":"Bipolar Disorder","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Bipolar_Disorder.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Bipolar_Disorder.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Bipolar_Disorder.html#dataset-massive-msv000086425"]},{"id":"dataset:massive:msv000086739","accession":"massive:MSV000086739","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000086739","title":"Combined Inhibition of AKT and KIT Restores Expression of Programmed Cell Death 4 (PDCD4) in Gastrointestinal Stromal Tumor","alternate_titles":[],"description":"AKT activation is a hallmark of IM resistance in GIST. The presence of an additional therapeutic agent could potentially suppress the growth and survival of a clone of cancer cells, which have developed resistance to IM. Simultaneous targeting of AKT in addition to inhibiting KIT with IM has potential to be a promising strategy to prevent the development of secondary resistance to IM.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Gastrointestinal Stromal Tumor\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Gastrointestinal_Stromal_Tumor","name":"Gastrointestinal Stromal Tumor","kind":"Disorder","source_path":"kb/disorders/Gastrointestinal_Stromal_Tumor.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Gastrointestinal_Stromal_Tumor.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Gastrointestinal_Stromal_Tumor.html#dataset-massive-msv000086739"}],"context_names":["Gastrointestinal Stromal Tumor"],"disease_names":["Gastrointestinal Stromal Tumor"],"disease_name":"Gastrointestinal Stromal Tumor","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Gastrointestinal_Stromal_Tumor.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Gastrointestinal_Stromal_Tumor.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Gastrointestinal_Stromal_Tumor.html#dataset-massive-msv000086739"]},{"id":"dataset:massive:msv000086842","accession":"massive:MSV000086842","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000086842","title":"The B Cell Repertoire in Multiple Sclerosis Reveals Molecular Mimicry between EBNA1 and GlialCAM","alternate_titles":[],"description":"This data set contains the mass spectrometry raw files for the paper The B Cell Repertoire in Multiple Sclerosis Reveals Molecular Mimicry between EBNA1 and GlialCAM. In multiple sclerosis (MS) intrathecal B lymphocytes are directly involved in inflammation and secrete oligoclonal immunoglobulin. However, our understanding of their phenotype, function, and antigen-specificity in MS is incomplete. Molecular mimicry to viruses and self-antigens could be a trigger of autoimmunity.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Multiple Sclerosis\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Multiple_Sclerosis","name":"Multiple Sclerosis","kind":"Disorder","source_path":"kb/disorders/Multiple_Sclerosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Multiple_Sclerosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Multiple_Sclerosis.html#dataset-massive-msv000086842"}],"context_names":["Multiple Sclerosis"],"disease_names":["Multiple Sclerosis"],"disease_name":"Multiple Sclerosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Multiple_Sclerosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Multiple_Sclerosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Multiple_Sclerosis.html#dataset-massive-msv000086842"]},{"id":"dataset:massive:msv000086975","accession":"massive:MSV000086975","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000086975","title":"Schizophrenia Plasma Metabolome Analysis","alternate_titles":[],"description":"Metabolomics analysis of plasma collected from patients with schizophrenia and non-psychiatric control subjects.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Schizophrenia\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Schizophrenia","name":"Schizophrenia","kind":"Disorder","source_path":"kb/disorders/Schizophrenia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Schizophrenia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Schizophrenia.html#dataset-massive-msv000086975"}],"context_names":["Schizophrenia"],"disease_names":["Schizophrenia"],"disease_name":"Schizophrenia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Schizophrenia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Schizophrenia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Schizophrenia.html#dataset-massive-msv000086975"]},{"id":"dataset:massive:msv000086977","accession":"massive:MSV000086977","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000086977","title":"Schizophrenia Proteome Data High Resolution Method","alternate_titles":[],"description":"PTM-tolerant quantitative proteome analysis of plasma collected from schizophrenia patients and nonspychiatric healthy controls.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Schizophrenia\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Schizophrenia","name":"Schizophrenia","kind":"Disorder","source_path":"kb/disorders/Schizophrenia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Schizophrenia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Schizophrenia.html#dataset-massive-msv000086977"}],"context_names":["Schizophrenia"],"disease_names":["Schizophrenia"],"disease_name":"Schizophrenia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Schizophrenia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Schizophrenia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Schizophrenia.html#dataset-massive-msv000086977"]},{"id":"dataset:massive:msv000087251","accession":"massive:MSV000087251","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000087251","title":"Systematic evaluation and modulation of HLA class I downregulation in Merkel cell carcinoma","alternate_titles":[],"description":"Lee PC, Klaeger S, Le PM, Korthauer K, Cheng J, Wong A, Tarren A, Lemvigh C, Sarkizova S, Li L, Frost TC, Nomburg J, Liu X, Pomerance L, Doherty L, Witten E, Zhang W, Apffel A, Wallace L, Neuberg D, Olsen L, Thakuria M, Clauser K, Starrett G, Doench J, Buhrlage SJ, Carr SA, DeCaprio JA, Wu CJ, Keskin DB. 2021 Viruses avoid immune surveillance through an array of mechanisms, including perturbation of HLA class I (HLA I) antigen presentation.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Merkel Cell Carcinoma\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Merkel_Cell_Carcinoma","name":"Merkel Cell Carcinoma","kind":"Disorder","source_path":"kb/disorders/Merkel_Cell_Carcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Merkel_Cell_Carcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Merkel_Cell_Carcinoma.html#dataset-massive-msv000087251"}],"context_names":["Merkel Cell Carcinoma"],"disease_names":["Merkel Cell Carcinoma"],"disease_name":"Merkel Cell Carcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Merkel_Cell_Carcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Merkel_Cell_Carcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Merkel_Cell_Carcinoma.html#dataset-massive-msv000087251"]},{"id":"dataset:massive:msv000087437","accession":"massive:MSV000087437","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000087437","title":"Proteomics of Primary Uveal Melanoma:Insights to Metastasis and Protein Biomarkers","alternate_titles":[],"description":"Uveal melanoma metastases are lethal and remain incurable. Quantitative proteomic analysis of 53 metastasizing and 47 non-metastasizing primary uveal melanoma (pUM) was pursued for insights into UM metastasis and protein biomarkers. The metastatic status of the pUM specimens was defined based on clinical data, survival histories, prognostic analyses, and liver histopathology.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Uveal Melanoma\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Uveal_Melanoma","name":"Uveal Melanoma","kind":"Disorder","source_path":"kb/disorders/Uveal_Melanoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Uveal_Melanoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Uveal_Melanoma.html#dataset-massive-msv000087437"}],"context_names":["Uveal Melanoma"],"disease_names":["Uveal Melanoma"],"disease_name":"Uveal Melanoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Uveal_Melanoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Uveal_Melanoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Uveal_Melanoma.html#dataset-massive-msv000087437"]},{"id":"dataset:massive:msv000087837","accession":"massive:MSV000087837","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000087837","title":"Local and systemic changes in lipid profile as potential biomarkers for canine atopic dermatitis.","alternate_titles":[],"description":"Lipids play a critical role in the skin as components of the epidermal barrier and as sig-naling molecules. Atopic dermatitis in dogs is associated with changes in the lipid composition of the skin, but whether these precede the onset of dermatitis or occur secondary to the dermatitis is unclear. We applied rapid lipid profiling mass spectrometry methods to skin and blood samples of dogs and determined changes following systemic treatment. Thirty control dogs and 30 atopic dogs with mild to moderate dermatitis were enrolled.","alternate_descriptions":[],"data_types":["METABOLOMICS"],"data_type_labels":["Metabolite profiling"],"data_type_label":"Metabolite profiling","organisms":[{"id":"NCBITaxon:9615","label":"Canis lupus familiaris","display_label":"dog","url":"http://purl.obolibrary.org/obo/NCBITaxon_9615"}],"organism_labels":["Canis lupus familiaris"],"organism_label":"Canis lupus familiaris","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Atopic Dermatitis\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Atopic_Dermatitis","name":"Atopic Dermatitis","kind":"Disorder","source_path":"kb/disorders/Atopic_Dermatitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Atopic_Dermatitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Atopic_Dermatitis.html#dataset-massive-msv000087837"}],"context_names":["Atopic Dermatitis"],"disease_names":["Atopic Dermatitis"],"disease_name":"Atopic Dermatitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Atopic_Dermatitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Atopic_Dermatitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Atopic_Dermatitis.html#dataset-massive-msv000087837"]},{"id":"dataset:massive:msv000087986","accession":"massive:MSV000087986","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000087986","title":"Proteomics of high density lipoprotein subfractions in type 1 diabetes mellitus and controls","alternate_titles":[],"description":"Toyoshima MTK. Proteomics and functionality of high-density lipoprotein subfractions and subclinical cardiovascular disease in type 1 diabetes mellitus. Faculdade de Medicina, Universidade de Sao Paulo 2021.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"type 1 diabetes mellitus\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Type_I_Diabetes","name":"Type I Diabetes","kind":"Disorder","source_path":"kb/disorders/Type_I_Diabetes.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Type_I_Diabetes.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Type_I_Diabetes.html#dataset-massive-msv000087986"}],"context_names":["Type I Diabetes"],"disease_names":["Type I Diabetes"],"disease_name":"Type I Diabetes","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Type_I_Diabetes.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Type_I_Diabetes.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Type_I_Diabetes.html#dataset-massive-msv000087986"]},{"id":"dataset:massive:msv000088237","accession":"massive:MSV000088237","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000088237","title":"Integrated proteomic and metabolomic analyses of the mitochondrial neurodegenerative disease MELAS","alternate_titles":[],"description":"Paired global proteomics (data-dependent acquisition verified by data-independent acquisition) and polar plus nonpolar metabolomics of patient-derived dermal fibroblasts carrying the ultra-rare MELAS variant m.14453G>A in MT-ND6, a complex I structural subunit, against control.","alternate_descriptions":[],"data_types":["MULTI_OMICS"],"data_type_labels":["Multi Omics"],"data_type_label":"Multi Omics","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:34982085"],"publication_contexts":[{"context_id":"disorder:MELAS_Syndrome","publication":"PMID:34982085"}],"publication":"PMID:34982085","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34982085","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:34982085","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/34982085","reference_title":"Integrated proteomic and metabolomic analyses of the mitochondrial neurodegenerative disease MELAS.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The most clinically relevant discovery is the downregulation of the arginine biosynthesis pathway, likely due to blocked argininosuccinate synthase, which is congruent with the MELAS cardinal symptom of stroke-like episodes and its current treatment by arginine infusion.","explanation":"Supplies a cell-intrinsic biosynthetic mechanism for arginine deficiency, distinct from the plasma-level observations the arginine rationale currently rests on."},{"reference":"PMID:34982085","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/34982085","reference_title":"Integrated proteomic and metabolomic analyses of the mitochondrial neurodegenerative disease MELAS.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"The pathogenic mechanism of MELAS remains enigmatic due to the exceptional clinical heterogeneity and the obscure genotype-phenotype correlation among MELAS patients.","explanation":"The authors frame the study against the same genotype-phenotype gap this entry records."}],"notes":["Two things make this worth more than its single-patient design. It is the only public patient-tissue multi-omics deposit found for a non-m.3243A>G MELAS genotype, so it speaks to the allele arm of the genotype-phenotype gap and to the complex I subunit subtype curated in this entry. And it reports downregulated arginine biosynthesis through blocked argininosuccinate synthase - a cell-intrinsic route to arginine deficiency, which is a different claim from the reduced plasma arginine that the existing therapeutic rationale rests on. One patient and one ultra-rare variant; the authors call it proof-of-principle and say validation in a larger cohort is still needed."],"contexts":[{"id":"disorder:MELAS_Syndrome","name":"MELAS Syndrome","kind":"Disorder","source_path":"kb/disorders/MELAS_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MELAS_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/MELAS_Syndrome.html#dataset-massive-msv000088237"}],"context_names":["MELAS Syndrome"],"disease_names":["MELAS Syndrome"],"disease_name":"MELAS Syndrome","same_context_model_ids":["model:kb/disorders/MELAS_Syndrome.yaml:m.3243A>G patient iPSC-derived neurons"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/MELAS_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/MELAS_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/MELAS_Syndrome.html#dataset-massive-msv000088237"]},{"id":"dataset:massive:msv000088254","accession":"massive:MSV000088254","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000088254","title":"The Mycobacterium tuberculosis O-phosphorylation landscape","alternate_titles":[],"description":"LC-MS/MS tryptic peptide data comprising both label free (phosphoproteome) and TMT10 (global and phosphoproteome) analysis of mycobacterium tuberculosis mutants (WT, GoF, and LoF) grown at stationary phase. Data was searched with MS-GF+ (TMT) and MaxQuant (label free).","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Tuberculosis\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Tuberculosis","name":"Tuberculosis","kind":"Disorder","source_path":"kb/disorders/Tuberculosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Tuberculosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Tuberculosis.html#dataset-massive-msv000088254"}],"context_names":["Tuberculosis"],"disease_names":["Tuberculosis"],"disease_name":"Tuberculosis","same_context_model_ids":["model:kb/disorders/Tuberculosis.yaml:Autologous iPSC-derived alveolus-on-chip (iLoC) Mtb infection model"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Tuberculosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Tuberculosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Tuberculosis.html#dataset-massive-msv000088254"]},{"id":"dataset:massive:msv000088329","accession":"massive:MSV000088329","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000088329","title":"Combined targeted and untargeted high-resolution mass spectrometry analyses to investigate metabolic alterations in Pompe disease","alternate_titles":[],"description":"Pompe disease is a rare, lysosomal disorder, characterized by intra-lysosomal glycogen accumulation due to an impaired function of ?-glucosidase enzyme. The laboratory testing for Pompe is usually performed by enzyme activity, genetic test, or urine glucose tetrasaccharide (Glc4) screening by HPLC. Despite being a good preliminary marker, the Glc4 is not specific for Pompe.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Pompe Disease\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Pompe_Disease","name":"Pompe Disease","kind":"Disorder","source_path":"kb/disorders/Pompe_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pompe_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pompe_Disease.html#dataset-massive-msv000088329"}],"context_names":["Pompe Disease"],"disease_names":["Pompe Disease"],"disease_name":"Pompe Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Pompe_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pompe_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Pompe_Disease.html#dataset-massive-msv000088329"]},{"id":"dataset:massive:msv000088508","accession":"massive:MSV000088508","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000088508","title":"TAILS identifies candidate substrates and biomarkers of ADAMTS7, a therapeutic protease target in coronary artery disease","alternate_titles":[],"description":"MacDonald BT, Keshishian H, Mundorff CC, Arduini A, Lai D, Bendinelli K, Popp NR, Bhandary B, Clauser KR, Specht H, Elowe NH, Laprise D, Xing Y, Kaushik VK, Carr SA, Ellinor PT. Loss-of-function mutations in the secreted enzyme ADAMTS7 (a disintegrin and metalloproteinase with thrombospondin motifs 7) are associated with protection for coronary artery disease (CAD). ADAMTS7 catalytic inhibition has been proposed as a therapeutic strategy for treating CAD; however, the lack of an endogenous substrate has hindered the development of activity-based biomarkers.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Coronary Artery Disease\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Coronary_Artery_Disease","name":"Coronary Artery Disease","kind":"Disorder","source_path":"kb/disorders/Coronary_Artery_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Coronary_Artery_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Coronary_Artery_Disease.html#dataset-massive-msv000088508"}],"context_names":["Coronary Artery Disease"],"disease_names":["Coronary Artery Disease"],"disease_name":"Coronary Artery Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Coronary_Artery_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Coronary_Artery_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Coronary_Artery_Disease.html#dataset-massive-msv000088508"]},{"id":"dataset:massive:msv000088551","accession":"massive:MSV000088551","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000088551","title":"Pilot Study Evaluating Everolimus Molecular Mechanisms in Tuberous Sclerosis Complex (TSC) and Focal Cortical Dysplasia (FCD)","alternate_titles":[],"description":"Treatment resistant epilepsy in tuberous sclerosis complex (TSC) and some focal cortical dysplasias (FCDs) are associated with dysfunctional mammalian target of rapamycin (mTOR) signaling. This can upregulate cell growth and proliferation, with increased downstream ribosomal S6 protein phosphorylation (phospho-S6). mTOR inhibitors are used in TSC, the archetypal mTORopathy, to reduce tumor growth or seizure frequency. Preclinical studies in FCD support a potential role in suppressing seizures.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Tuberous Sclerosis Complex\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Tuberous_Sclerosis_Complex","name":"Tuberous Sclerosis Complex","kind":"Disorder","source_path":"kb/disorders/Tuberous_Sclerosis_Complex.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Tuberous_Sclerosis_Complex.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Tuberous_Sclerosis_Complex.html#dataset-massive-msv000088551"}],"context_names":["Tuberous Sclerosis Complex"],"disease_names":["Tuberous Sclerosis Complex"],"disease_name":"Tuberous Sclerosis Complex","same_context_model_ids":["model:kb/disorders/Tuberous_Sclerosis_Complex.yaml:CRISPR-engineered TSC2 conditional-biallelic human cortical spheroids","model:kb/disorders/Tuberous_Sclerosis_Complex.yaml:TSC human cerebral organoids with caudal late interneuron progenitor (CLIP) over-proliferation","model:kb/disorders/Tuberous_Sclerosis_Complex.yaml:TSC patient-derived neurovascular unit (iPSC blood-brain-barrier chip)"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Tuberous_Sclerosis_Complex.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Tuberous_Sclerosis_Complex.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Tuberous_Sclerosis_Complex.html#dataset-massive-msv000088551"]},{"id":"dataset:massive:msv000088553","accession":"massive:MSV000088553","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000088553","title":"Site specific glycan analysis of hepatitis C virus E1E2 glycoprotein complex","alternate_titles":[],"description":"Dataset for N-linked glycosylation analysis contained within \"Structure of the hepatitis C virus E1E2 glycoprotein complex\"","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Hepatitis C\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Hepatitis_C","name":"Hepatitis C","kind":"Disorder","source_path":"kb/disorders/Hepatitis_C.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatitis_C.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hepatitis_C.html#dataset-massive-msv000088553"}],"context_names":["Hepatitis C"],"disease_names":["Hepatitis C"],"disease_name":"Hepatitis C","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hepatitis_C.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hepatitis_C.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hepatitis_C.html#dataset-massive-msv000088553"]},{"id":"dataset:massive:msv000088713","accession":"massive:MSV000088713","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000088713","title":"Retinal pigment epithelium extracellular vesicles are potent inducers of age-related macular degeneration disease phenotype in the outer retina","alternate_titles":[],"description":"Age-related macular degeneration (AMD) is a leading cause of blindness. Vision loss is caused by the loss of the retinal pigment epithelium (RPE) and photoreceptors and/or retinal and choroidal angiogenesis. Here we use AMD patient specific RPE cells with the Y402H high-risk polymorphism in the complement factor H to perform a comprehensive analysis of EVs, their cargo and role in disease pathology. We show that AMD RPE is characterised by enhanced and polarised EV secretion.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Age-Related Macular Degeneration\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Age_Related_Macular_Degeneration","name":"Age-Related Macular Degeneration","kind":"Disorder","source_path":"kb/disorders/Age_Related_Macular_Degeneration.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Age_Related_Macular_Degeneration.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Age-Related_Macular_Degeneration.html#dataset-massive-msv000088713"}],"context_names":["Age-Related Macular Degeneration"],"disease_names":["Age-Related Macular Degeneration"],"disease_name":"Age-Related Macular Degeneration","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Age_Related_Macular_Degeneration.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Age_Related_Macular_Degeneration.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Age-Related_Macular_Degeneration.html#dataset-massive-msv000088713"]},{"id":"dataset:massive:msv000088992","accession":"massive:MSV000088992","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000088992","title":"Ex vivo drug response heterogeneity reveals personalized therapeutic strategies for patients with multiple myeloma","alternate_titles":[],"description":"Multiple myeloma (MM) is a plasma cell malignancy defined by complex genetics and extensive patient heterogeneity. Despite a growing arsenal of approved therapies, MM remains incurable and in need of guidelines to identify effective personalized treatments. Here, we survey the ex vivo drug and immunotherapy sensitivities across 101 bone marrow (BM) samples from 70 MM patients using multiplexed immunofluorescence, automated microscopy and deep learning-based single-cell phenotyping.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Multiple Myeloma\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Multiple_Myeloma","name":"Multiple Myeloma","kind":"Disorder","source_path":"kb/disorders/Multiple_Myeloma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Multiple_Myeloma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Multiple_Myeloma.html#dataset-massive-msv000088992"}],"context_names":["Multiple Myeloma"],"disease_names":["Multiple Myeloma"],"disease_name":"Multiple Myeloma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Multiple_Myeloma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Multiple_Myeloma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Multiple_Myeloma.html#dataset-massive-msv000088992"]},{"id":"dataset:massive:msv000089171","accession":"massive:MSV000089171","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000089171","title":"Organelle resolved proteomics reveals new chordoma cell surface markers required for proliferation and association with outcome","alternate_titles":[],"description":"Here, we used a proteomics approach to identify novel chordoma-specific cell-surface protein markers. Four established chordoma cell lines (U-CH17P, U-CH17M, U-CH17S and U-CH11R) were analyzed by quantitative proteomics using a comprehensive organellar fractionation approach based on differential ultracentrifugation. A subtractive proteomics strategy was applied to identify proteins that are plasma membrane enriched. The expression profiles of these cell-surface proteins were validated across chordoma cell lines, patient surgical tissue samples, and normal tissue lysates.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Chordoma\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Chordoma","name":"Chordoma","kind":"Disorder","source_path":"kb/disorders/Chordoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chordoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chordoma.html#dataset-massive-msv000089171"}],"context_names":["Chordoma"],"disease_names":["Chordoma"],"disease_name":"Chordoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chordoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chordoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chordoma.html#dataset-massive-msv000089171"]},{"id":"dataset:massive:msv000089203","accession":"massive:MSV000089203","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000089203","title":"Molecular Mechanisms in Rasmussen Encephalitis","alternate_titles":[],"description":"Rasmussen encephalitis is a unilateral encephalitis characterized by treatment-resistant epilepsy and progressive cognitive and motor decline. MRI reveals inflammation and neuropathology reveals reactive astrocytes, microglial activation, microglial nodules, T cell infiltration, and neuronal loss.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Rasmussen Encephalitis\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Rasmussen_Encephalitis","name":"Rasmussen Encephalitis","kind":"Disorder","source_path":"kb/disorders/Rasmussen_Encephalitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rasmussen_Encephalitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Rasmussen_Encephalitis.html#dataset-massive-msv000089203"}],"context_names":["Rasmussen Encephalitis"],"disease_names":["Rasmussen Encephalitis"],"disease_name":"Rasmussen Encephalitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Rasmussen_Encephalitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rasmussen_Encephalitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Rasmussen_Encephalitis.html#dataset-massive-msv000089203"]},{"id":"dataset:massive:msv000089312","accession":"massive:MSV000089312","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000089312","title":"The Behcet's disease risk variant HLA-B51/ ERAP1-Hap10 alters human CD8 T cell immunity","alternate_titles":[],"description":"The ERAP1 haplotype Hap10 encodes for a variant allotype of the ER-resident peptide-trimming aminopeptidase ERAP1 with low enzymatic activity resembling functional KO. This haplotype recessively confers the highest risk for Behcet's diseases (BD) currently known, but only in carriers of HLA-B*51, the classical risk factor for the disease. The mechanistic implications and biological consequences of this epistatic relationship are unknown. Here, we aimed to determine its biological relevance and functional impact, including its effect on the HLA-class I peptidome.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Behcet's Disease\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Behcets_Disease","name":"Behcet's Disease","kind":"Disorder","source_path":"kb/disorders/Behcets_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Behcets_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Behcet's_Disease.html#dataset-massive-msv000089312"}],"context_names":["Behcet's Disease"],"disease_names":["Behcet's Disease"],"disease_name":"Behcet's Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Behcets_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Behcets_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Behcet's_Disease.html#dataset-massive-msv000089312"]},{"id":"dataset:massive:msv000090255","accession":"massive:MSV000090255","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000090255","title":"Profiling of Kallikrein Proteases and Global Proteome Biology of PDAC, Chronic Pancreatitis and Normal Pancreas","alternate_titles":[],"description":"Cell conditioned medium from human pancreatic cancer cell lines MiaPaCa-2, AsPC-1, primary pancreatic cell lines as well as human FFPE tissue samples from pancreatic ductal adenocarcinoma (PDAC), chronic pancreatitis (CP), ampullary cancer, non-malignant adjacent pancreas and normal pancreas were analyzed via targeted (SRM, PRM) and/or explorative (DIA) mass spectrometry.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Chronic Pancreatitis\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Chronic_Pancreatitis","name":"Chronic Pancreatitis","kind":"Disorder","source_path":"kb/disorders/Chronic_Pancreatitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Pancreatitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chronic_Pancreatitis.html#dataset-massive-msv000090255"}],"context_names":["Chronic Pancreatitis"],"disease_names":["Chronic Pancreatitis"],"disease_name":"Chronic Pancreatitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chronic_Pancreatitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Pancreatitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chronic_Pancreatitis.html#dataset-massive-msv000090255"]},{"id":"dataset:massive:msv000090685","accession":"massive:MSV000090685","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000090685","title":"Proteomic Analysis of Cerebrospinal Fluids from Chronic Fatigue Syndrome Patients with and without Co-existing Fibromyalgia","alternate_titles":[],"description":"Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and fibromyalgia have overlapping neurologic symptoms particularly disabling fatigue. This has given rise to the question whether they are distinct central nervous system (CNS) entities or is one an extension of the other. To investigate this, we used unbiased quantitative mass spectrometry-based proteomics to examine the most proximal fluid to the brain, cerebrospinal fluid (CSF). This was to ascertain if the proteome profile of one was the same or different from the other.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Fibromyalgia\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Fibromyalgia","name":"Fibromyalgia","kind":"Disorder","source_path":"kb/disorders/Fibromyalgia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fibromyalgia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Fibromyalgia.html#dataset-massive-msv000090685"}],"context_names":["Fibromyalgia"],"disease_names":["Fibromyalgia"],"disease_name":"Fibromyalgia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Fibromyalgia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fibromyalgia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Fibromyalgia.html#dataset-massive-msv000090685"]},{"id":"dataset:massive:msv000090686","accession":"massive:MSV000090686","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000090686","title":"Dietary Grape Against Atopic Dermatitis in NC/NgaTndCrlj Mice: Proteomics Analysis","alternate_titles":[],"description":"The study demonstrates the effects of dietary grape powder against atopic dermatitis in 2,4-dinitrofluorobenzene-induced atopic dermatitis in NC/NgaTndCrlj mice. To uncover molecular mechanism(s) of biological responses of grape powder, dorsal skin samples from normal control (noAD), atopic dermatitis control (ctlAD) and 5% grape powder (5GP) prevention groups were analyzed using gel-free quantitative global proteomics analysis at the School of Pharmacy Analytical Instrumentation Facility, University of Wisconsin–Madison.","alternate_descriptions":[],"data_types":["PROTEOMICS"],"data_type_labels":["Protein expression profiling"],"data_type_label":"Protein expression profiling","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Atopic Dermatitis\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Atopic_Dermatitis","name":"Atopic Dermatitis","kind":"Disorder","source_path":"kb/disorders/Atopic_Dermatitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Atopic_Dermatitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Atopic_Dermatitis.html#dataset-massive-msv000090686"}],"context_names":["Atopic Dermatitis"],"disease_names":["Atopic Dermatitis"],"disease_name":"Atopic Dermatitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Atopic_Dermatitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Atopic_Dermatitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Atopic_Dermatitis.html#dataset-massive-msv000090686"]},{"id":"dataset:massive:msv000090700","accession":"massive:MSV000090700","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000090700","title":"Oncogenic pathways in uveal melanoma identified by phosphoproteomic analysis","alternate_titles":[],"description":"The uveal melanoma cell lines MP41 and MP46 driven by oncogenic G11 (Q209L) and Gq (Q209L), respectively, and a control cell line OCM-1A driven by oncogenic BRAF (V600E) were treated for 24 hours with FR900359, a highly specific inhibitor of Gq/11. Protein extracts were collected and TMT labeled prior to LC-MS analysis. The enrichment of phosphopeptides from fractions of each sample was performed using IMAC prior to LC-MS. Proteomic and phospho-proteomic data analyses were performed to identify changes in post-translational modification in signaling pathways regulated by Gq/11 in these cells.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Uveal Melanoma\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Uveal_Melanoma","name":"Uveal Melanoma","kind":"Disorder","source_path":"kb/disorders/Uveal_Melanoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Uveal_Melanoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Uveal_Melanoma.html#dataset-massive-msv000090700"}],"context_names":["Uveal Melanoma"],"disease_names":["Uveal Melanoma"],"disease_name":"Uveal Melanoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Uveal_Melanoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Uveal_Melanoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Uveal_Melanoma.html#dataset-massive-msv000090700"]},{"id":"dataset:massive:msv000090746","accession":"massive:MSV000090746","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000090746","title":"The NFIB/CARM1 Partnership is a Therapeutic Target for Small Cell Lung Cancer","alternate_titles":[],"description":"This project identified NFI family members as CARM1 substrates. NFIB was previously reported to play a critical role in the development of small cell lung cancer. We provided evidence that the arginine methylation of NFIB is required for its oncogenic function in small cell lung cancer.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Small Cell Lung Cancer\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Small_Cell_Lung_Cancer","name":"Small Cell Lung Cancer","kind":"Disorder","source_path":"kb/disorders/Small_Cell_Lung_Cancer.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Small_Cell_Lung_Cancer.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Small_Cell_Lung_Cancer.html#dataset-massive-msv000090746"}],"context_names":["Small Cell Lung Cancer"],"disease_names":["Small Cell Lung Cancer"],"disease_name":"Small Cell Lung Cancer","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Small_Cell_Lung_Cancer.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Small_Cell_Lung_Cancer.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Small_Cell_Lung_Cancer.html#dataset-massive-msv000090746"]},{"id":"dataset:massive:msv000090875","accession":"massive:MSV000090875","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000090875","title":"Protein profiles of fat biopsies from patients affected by AL amyloidosis and healthy controls.","alternate_titles":[],"description":"Abdominal subcutaneous adipose tissue protein profiles from control subjects, and ALK (Kappa) and ALL (Lambda) amyloidosis patients. Raw data were acquired by LTQ, Orbitrap and QExactive instruments. For major chromatographic details refers to doi:10.1182/blood-2011-07-365510, doi:10.3109/13506129.2012.674989, doi:10.3390/molecules26071913.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"AL Amyloidosis\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:AL_Amyloidosis","name":"Systemic AL Amyloidosis","kind":"Disorder","source_path":"kb/disorders/AL_Amyloidosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/AL_Amyloidosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Systemic_AL_Amyloidosis.html#dataset-massive-msv000090875"}],"context_names":["Systemic AL Amyloidosis"],"disease_names":["Systemic AL Amyloidosis"],"disease_name":"Systemic AL Amyloidosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/AL_Amyloidosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/AL_Amyloidosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Systemic_AL_Amyloidosis.html#dataset-massive-msv000090875"]},{"id":"dataset:massive:msv000091078","accession":"massive:MSV000091078","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000091078","title":"Proteomic analysis of Descemet's membrane with corneal endothelial cells derived from patients with Fuchs endothelial corneal dystrophy and healthy control subjects","alternate_titles":[],"description":"This dataset contains proteomic profiles of Descemet's membrane (DM) with corneal endothelial cells derived from patients with Fuchs endothelial corneal dystrophy (FECD) and non-FECD subjects by shotgun proteomics. FECD is the most common inherited corneal disease. Fibrillar focal excrescences, called guttae, and corneal edema due to corneal endothelial cell death result in progressive vision loss. Our dataset indicated that 32 distinctive molecules were expressed only in the FECD-DM but not in the DM of the control subject, possibly having important roles in the pathophysiology of FECD.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Fuchs Endothelial Corneal Dystrophy\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Fuchs_Endothelial_Corneal_Dystrophy","name":"Fuchs Endothelial Corneal Dystrophy","kind":"Disorder","source_path":"kb/disorders/Fuchs_Endothelial_Corneal_Dystrophy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fuchs_Endothelial_Corneal_Dystrophy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Fuchs_Endothelial_Corneal_Dystrophy.html#dataset-massive-msv000091078"}],"context_names":["Fuchs Endothelial Corneal Dystrophy"],"disease_names":["Fuchs Endothelial Corneal Dystrophy"],"disease_name":"Fuchs Endothelial Corneal Dystrophy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Fuchs_Endothelial_Corneal_Dystrophy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Fuchs_Endothelial_Corneal_Dystrophy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Fuchs_Endothelial_Corneal_Dystrophy.html#dataset-massive-msv000091078"]},{"id":"dataset:massive:msv000091370","accession":"massive:MSV000091370","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000091370","title":"Localized Proteomic Differences in Choroid Plexus of Alzheimers Disease and Epilepsy Patients","alternate_titles":[],"description":"Alzheimers disease and epilepsy are reciprocally related. Among sporadic AD patients, seizures occur in 10-22 percent, and subclinical epileptiform abnormalities occur in 22-5 percent. Cognitive deficits, with prominent short-term memory impairments, occur in most epilepsy patients. Common neurophysiological and molecular mechanisms occur in AD and epilepsy. Emerging evidence identifies choroid plexus pathological changes in aging, AD, and epilepsy.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Epilepsy\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Epilepsy","name":"Epilepsy","kind":"Disorder","source_path":"kb/disorders/Epilepsy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Epilepsy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Epilepsy.html#dataset-massive-msv000091370"}],"context_names":["Epilepsy"],"disease_names":["Epilepsy"],"disease_name":"Epilepsy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Epilepsy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Epilepsy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Epilepsy.html#dataset-massive-msv000091370"]},{"id":"dataset:massive:msv000091651","accession":"massive:MSV000091651","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000091651","title":"Oct4 re-expression in cervical cancer","alternate_titles":[],"description":"E7 modulates Oct4 re-expression in cervical cancer","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Cervical Cancer\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Cervical_Cancer","name":"Cervical Cancer","kind":"Disorder","source_path":"kb/disorders/Cervical_Cancer.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cervical_Cancer.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cervical_Cancer.html#dataset-massive-msv000091651"}],"context_names":["Cervical Cancer"],"disease_names":["Cervical Cancer"],"disease_name":"Cervical Cancer","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cervical_Cancer.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cervical_Cancer.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cervical_Cancer.html#dataset-massive-msv000091651"]},{"id":"dataset:massive:msv000092309","accession":"massive:MSV000092309","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000092309","title":"Towards the definition of the molecular hallmarks of Idiopathic Membranous Nephropathy in serum proteome: a DIA-PASEF approach","alternate_titles":[],"description":"Idiopathic Membranous Nephropathy (IMN) is a pathologically defined disorder of the glomerulus, primarily responsible for nephrotic syndromes (NS) in nondiabetic adults. The underlying molecular mechanisms are still not completely clarified. To explore possible molecular and functional signatures, an optimised MS-method based on next-generation data-independent-acquisition combined with ion-mobility was applied to serum of patients affected by IMN (n=15) or by other glomerulopathies (PN) (n=15).","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Membranous nephropathy\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Membranous_Nephropathy","name":"Membranous nephropathy","kind":"Disorder","source_path":"kb/disorders/Membranous_Nephropathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Membranous_Nephropathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Membranous_nephropathy.html#dataset-massive-msv000092309"}],"context_names":["Membranous nephropathy"],"disease_names":["Membranous nephropathy"],"disease_name":"Membranous nephropathy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Membranous_Nephropathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Membranous_Nephropathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Membranous_nephropathy.html#dataset-massive-msv000092309"]},{"id":"dataset:massive:msv000092401","accession":"massive:MSV000092401","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000092401","title":"LCMSMS Quantitation of HILIC Enriched N glycopeptides derived from low abundance serum glycoproteins in patients with Narcolepsy Type I","alternate_titles":[],"description":"Glycoproteomics analysis is always challenging because of low abundance and complex site-specific heterogeneity. Glycoproteins are involved in various biological processes such as cell signaling, adhesion, and cell cell communication and may serve as potential biomarkers when analyzing different diseases. Here, we study glycoproteins in Narcolepsy Type I disease, a variant of narcolepsy characterized by cataplexy the sudden onset of muscle weakness usually caused by strong emotions. There is currently no cure for this life-altering disease.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Narcolepsy\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Narcolepsy","name":"Narcolepsy","kind":"Disorder","source_path":"kb/disorders/Narcolepsy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Narcolepsy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Narcolepsy.html#dataset-massive-msv000092401"}],"context_names":["Narcolepsy"],"disease_names":["Narcolepsy"],"disease_name":"Narcolepsy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Narcolepsy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Narcolepsy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Narcolepsy.html#dataset-massive-msv000092401"]},{"id":"dataset:massive:msv000092415","accession":"massive:MSV000092415","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000092415","title":"Proteomics analysis of the brain from a Gaucher disease mouse identifies pathological pathways including a possible role for transglutaminase 1","alternate_titles":[],"description":"Gaucher disease (GD) is caused by the defective activity of acid beta-glucosidase (GCase) which results from mutations in GBA1. Neurological forms of GD (nGD) can be generated in mice by intra-peritoneal injection of conduritol B-epoxide (CBE) which irreversibly inhibits GCase. Using this approach, a number of pathological pathways have been identified in mouse brain by RNAseq analysis. However, unlike transcriptomics, proteomics gives information about protein expression which is more likely to provide insight into which cellular pathways may be impacted in disease.","alternate_descriptions":[],"data_types":["PROTEOMICS"],"data_type_labels":["Protein expression profiling"],"data_type_label":"Protein expression profiling","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Gaucher Disease\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Gaucher_Disease","name":"Gaucher Disease","kind":"Disorder","source_path":"kb/disorders/Gaucher_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Gaucher_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Gaucher_Disease.html#dataset-massive-msv000092415"}],"context_names":["Gaucher Disease"],"disease_names":["Gaucher Disease"],"disease_name":"Gaucher Disease","same_context_model_ids":["model:kb/disorders/Gaucher_Disease.yaml:CBE-treated murine macrophage conditioned-medium model","model:kb/disorders/Gaucher_Disease.yaml:GD1 patient bone marrow stromal cells"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Gaucher_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Gaucher_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Gaucher_Disease.html#dataset-massive-msv000092415"]},{"id":"dataset:massive:msv000092457","accession":"massive:MSV000092457","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000092457","title":"Metabolic and Proteomic Changes in Sickle Cell Disease and thalassemia Mouse Splenic and Hepatic Macrophages and Peripheral Blood Mononuclear cells","alternate_titles":[],"description":"Sickle cell disease and Beta-thalassemia represent hemoglobinopathies arising from dysfunctional or under produced beta-globin chains, respectively. In both diseases, red blood cell injury and anemia are the impetus for end organ injury. Because persistent erythrophagocytosis is a hallmark of these genetic maladies it is critical to understand how macrophage phenotype polarizations in tissue compartments can inform on disease progression. Murine models of sickle cell disease and Beta-thalassemia allow for a basic understanding of mechanisms and provide for translation to human disease.","alternate_descriptions":[],"data_types":["MULTI_OMICS"],"data_type_labels":["Multi Omics"],"data_type_label":"Multi Omics","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Sickle Cell Disease\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Sickle_Cell_Disease","name":"Sickle Cell Disease","kind":"Disorder","source_path":"kb/disorders/Sickle_Cell_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sickle_Cell_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Sickle_Cell_Disease.html#dataset-massive-msv000092457"}],"context_names":["Sickle Cell Disease"],"disease_names":["Sickle Cell Disease"],"disease_name":"Sickle Cell Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Sickle_Cell_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sickle_Cell_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Sickle_Cell_Disease.html#dataset-massive-msv000092457"]},{"id":"dataset:massive:msv000092638","accession":"massive:MSV000092638","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000092638","title":"MALDI-IM-MS Imaging of Brain Sterols and Lipids in a Mouse Model of Smith-Lemli-Opitz Syndrome","alternate_titles":[],"description":"Spatial distribution of sterols and lipids in tissue sections of WT and SLOS (Dhcr7-KO) mouse brain analyzed by Waters Synapt XS-TWIM QTOF. Raw data files included for two biological replicates in positive ionization mode and negative ionization mode. .extern files in .raw folders contain specific instrumental parameters.","alternate_descriptions":[],"data_types":["METABOLOMICS"],"data_type_labels":["Metabolite profiling"],"data_type_label":"Metabolite profiling","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Smith-Lemli-Opitz syndrome\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Smith-Lemli-Opitz_syndrome","name":"Smith-Lemli-Opitz syndrome","kind":"Disorder","source_path":"kb/disorders/Smith-Lemli-Opitz_syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Smith-Lemli-Opitz_syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Smith-Lemli-Opitz_syndrome.html#dataset-massive-msv000092638"}],"context_names":["Smith-Lemli-Opitz syndrome"],"disease_names":["Smith-Lemli-Opitz syndrome"],"disease_name":"Smith-Lemli-Opitz syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Smith-Lemli-Opitz_syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Smith-Lemli-Opitz_syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Smith-Lemli-Opitz_syndrome.html#dataset-massive-msv000092638"]},{"id":"dataset:massive:msv000092967","accession":"massive:MSV000092967","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000092967","title":"Identifying Serum Metabolomic Markers Associated with Skin Disease Activity in patients with Psoriatic Arthritis","alternate_titles":[],"description":"This dataset contains .RAW files acquired for the paper: Identifying Serum Metabolomic Markers Associated with Skin Disease Activity in patients with Psoriatic Arthritis.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Psoriatic Arthritis\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Psoriatic_Arthritis","name":"Psoriatic Arthritis","kind":"Disorder","source_path":"kb/disorders/Psoriatic_Arthritis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Psoriatic_Arthritis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Psoriatic_Arthritis.html#dataset-massive-msv000092967"}],"context_names":["Psoriatic Arthritis"],"disease_names":["Psoriatic Arthritis"],"disease_name":"Psoriatic Arthritis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Psoriatic_Arthritis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Psoriatic_Arthritis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Psoriatic_Arthritis.html#dataset-massive-msv000092967"]},{"id":"dataset:massive:msv000093031","accession":"massive:MSV000093031","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000093031","title":"Untargeted UHPLC-MS/MS screen of pouchitis patient 207 feces from 'Microbially-catalyzed conjugation of GABA and tyramine to bile acids'","alternate_titles":[],"description":"Untargeted UPLC-MS/MS data from a screen of pouchitis patient 207 feces across seven time points. All using positive ionization.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Pouchitis\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Pouchitis","name":"Pouchitis","kind":"Disorder","source_path":"kb/disorders/Pouchitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pouchitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Pouchitis.html#dataset-massive-msv000093031"}],"context_names":["Pouchitis"],"disease_names":["Pouchitis"],"disease_name":"Pouchitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Pouchitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Pouchitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Pouchitis.html#dataset-massive-msv000093031"]},{"id":"dataset:massive:msv000093299","accession":"massive:MSV000093299","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000093299","title":"mitochondrial and dengue virus_2023","alternate_titles":[],"description":"Dengue virus non-structural protein 3 inhibits mitochondrial respiration by impairing complex I function","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Dengue\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Dengue","name":"Dengue","kind":"Disorder","source_path":"kb/disorders/Dengue.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dengue.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Dengue.html#dataset-massive-msv000093299"}],"context_names":["Dengue"],"disease_names":["Dengue"],"disease_name":"Dengue","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Dengue.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dengue.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Dengue.html#dataset-massive-msv000093299"]},{"id":"dataset:massive:msv000093453","accession":"massive:MSV000093453","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000093453","title":"O-GlcNAc Containing Proteins in Normal and Idiopathic Pulmonary Fibrosis Human Fibroblasts","alternate_titles":[],"description":"Isolated normal and IPF fibroblasts were homogenized in cold MilliQ water using a bullet blender. Samples were centrifuged and inhibitors were added: HALT (Thermo Fisher Scientific), Z-Pugnac (Tocris), Thiamet G (Cayman Chemicals), and benzonase (E1014, Millipore, Sigma). O-GlcNAc enzymatic labeling and protein capturing was performed as described using a Click-IT enrichment kit following the manufacturer's protocol (cat no: C33368, C33372, and C10416; Thermo Fisher Scientific).","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Idiopathic Pulmonary Fibrosis\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Idiopathic_Pulmonary_Fibrosis","name":"Idiopathic Pulmonary Fibrosis","kind":"Disorder","source_path":"kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Idiopathic_Pulmonary_Fibrosis.html#dataset-massive-msv000093453"}],"context_names":["Idiopathic Pulmonary Fibrosis"],"disease_names":["Idiopathic Pulmonary Fibrosis"],"disease_name":"Idiopathic Pulmonary Fibrosis","same_context_model_ids":["model:kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml:Immune-cell-free AT2-lineage and fibroblast organoids","model:kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml:Microengineered alveolar array lung-on-chip with breathing mechanics"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Idiopathic_Pulmonary_Fibrosis.html#dataset-massive-msv000093453"]},{"id":"dataset:massive:msv000093653","accession":"massive:MSV000093653","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000093653","title":"Raw data for manuscript : \"Serine synthesis via reversed SHMT2 activity drives glycine depletion and acetaminophen hepatotoxicity in MASLD\"","alternate_titles":[],"description":"Metabolic dysfunction-associated steatotic liver disease (MASLD) affects one third of the global population. 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The levels of glycine, a central component of one-carbon metabolism, were lower in mice with hepatic steatosis, consistent with clinical evidence.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. 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Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Acetaminophen_Hepatotoxicity","name":"Acetaminophen Hepatotoxicity","kind":"Disorder","source_path":"kb/disorders/Acetaminophen_Hepatotoxicity.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Acetaminophen_Hepatotoxicity.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Acetaminophen_Hepatotoxicity.html#dataset-massive-msv000093653"}],"context_names":["Acetaminophen Hepatotoxicity"],"disease_names":["Acetaminophen Hepatotoxicity"],"disease_name":"Acetaminophen Hepatotoxicity","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Acetaminophen_Hepatotoxicity.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Acetaminophen_Hepatotoxicity.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Acetaminophen_Hepatotoxicity.html#dataset-massive-msv000093653"]},{"id":"dataset:massive:msv000093698","accession":"massive:MSV000093698","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000093698","title":"Chemogenetic restoration of astrocyte morphology is beneficial in obsessive-compulsive disorder","alternate_titles":[],"description":"In vivo chemogenetic activation of astrocytes in the striatum via an engineered Gi-protein-coupled receptor was conducted in wild-type and SAPAP3 KO OCD mice. 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Matched because the disease is named in the dataset's own title (\"Obsessive-Compulsive Disorder\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Obsessive-Compulsive_Disorder","name":"Obsessive-Compulsive Disorder","kind":"Disorder","source_path":"kb/disorders/Obsessive-Compulsive_Disorder.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Obsessive-Compulsive_Disorder.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Obsessive-Compulsive_Disorder.html#dataset-massive-msv000093698"}],"context_names":["Obsessive-Compulsive Disorder"],"disease_names":["Obsessive-Compulsive Disorder"],"disease_name":"Obsessive-Compulsive Disorder","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Obsessive-Compulsive_Disorder.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Obsessive-Compulsive_Disorder.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Obsessive-Compulsive_Disorder.html#dataset-massive-msv000093698"]},{"id":"dataset:massive:msv000093893","accession":"massive:MSV000093893","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000093893","title":"Nontargeted plasma proteomics analysis uncovers candidate biomarkers for renal disease and pulmonary hypertension in patients with sickle cell disease","alternate_titles":[],"description":"Fifteen microliters of plasma from sickle cell disease patients, and pooled samples, were diluted with 5% deoxycholate and 10 mM DTT, followed by heating at 80 degC for 30 min, alkylation with 25 mM iodoacteamide and digestion with modified trypsin for 4 h at 37 degC. After acidification, samples were filtered.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Sickle Cell Disease\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Sickle_Cell_Disease","name":"Sickle Cell Disease","kind":"Disorder","source_path":"kb/disorders/Sickle_Cell_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sickle_Cell_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Sickle_Cell_Disease.html#dataset-massive-msv000093893"}],"context_names":["Sickle Cell Disease"],"disease_names":["Sickle Cell Disease"],"disease_name":"Sickle Cell Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Sickle_Cell_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Sickle_Cell_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Sickle_Cell_Disease.html#dataset-massive-msv000093893"]},{"id":"dataset:massive:msv000094293","accession":"massive:MSV000094293","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000094293","title":"Minimal Change Disease: a proteomics approach","alternate_titles":[],"description":"This study aimed to shed light on the potential pathophysiology of MCD by using glomerular proteomic analysis. 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Glomeruli were excised from FFPE renal biopsies using laser capture microdissection (LCM), and a single-pot solid-phase-enhanced sample preparation (SP3) digest method was used to improve yield and protein identifications.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. 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Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Minimal_Change_Disease","name":"Minimal Change Disease","kind":"Disorder","source_path":"kb/disorders/Minimal_Change_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Minimal_Change_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Minimal_Change_Disease.html#dataset-massive-msv000094293"}],"context_names":["Minimal Change Disease"],"disease_names":["Minimal Change Disease"],"disease_name":"Minimal Change Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Minimal_Change_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Minimal_Change_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Minimal_Change_Disease.html#dataset-massive-msv000094293"]},{"id":"dataset:massive:msv000094311","accession":"massive:MSV000094311","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000094311","title":"Top-Down Proteomics Identifies Plasma Proteoform Signatures of Liver Cirrhosis Progression","alternate_titles":[],"description":"Cirrhosis, advanced liver disease, affects 2-5 million Americans. While most patients have compensated cirrhosis and may be fairly asymptomatic, many decompensate and experience life-threatening complications such as gastrointestinal bleeding, confusion (hepatic encephalopathy), and ascites, reducing life expectancy from 12 to less than 2 years. Among the patients with compensated cirrhosis, identifying patients at high risk of decompensation is critical to optimize care, reduce morbidity and mortality.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. 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Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Liver_Cirrhosis","name":"Liver Cirrhosis","kind":"Disorder","source_path":"kb/disorders/Liver_Cirrhosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Liver_Cirrhosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Liver_Cirrhosis.html#dataset-massive-msv000094311"}],"context_names":["Liver Cirrhosis"],"disease_names":["Liver Cirrhosis"],"disease_name":"Liver Cirrhosis","same_context_model_ids":["model:kb/disorders/Liver_Cirrhosis.yaml:Akura Twin 384-well liver fibrosis microphysiological system (HepaRG/THP-1 and hTERT-HSC microtissues)"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Liver_Cirrhosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Liver_Cirrhosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Liver_Cirrhosis.html#dataset-massive-msv000094311"]},{"id":"dataset:massive:msv000094400","accession":"massive:MSV000094400","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000094400","title":"Differences in the Cerebral Amyloid Angiopathy Proteome in Alzheimers Disease and Mild Cognitive Impairment","alternate_titles":[],"description":"Quantitative label-free proteomics study comparing brain samples from subjects with Cerebral amyloid angiopathy, Alzheimer desease and healthy Control groups.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. 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Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Cerebral_Amyloid_Angiopathy","name":"Cerebral Amyloid Angiopathy","kind":"Disorder","source_path":"kb/disorders/Cerebral_Amyloid_Angiopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cerebral_Amyloid_Angiopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cerebral_Amyloid_Angiopathy.html#dataset-massive-msv000094400"}],"context_names":["Cerebral Amyloid Angiopathy"],"disease_names":["Cerebral Amyloid Angiopathy"],"disease_name":"Cerebral Amyloid Angiopathy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Cerebral_Amyloid_Angiopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cerebral_Amyloid_Angiopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cerebral_Amyloid_Angiopathy.html#dataset-massive-msv000094400"]},{"id":"dataset:massive:msv000094401","accession":"massive:MSV000094401","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000094401","title":"Proteomic profile of hippocampus regions from the pilocarpine medial temporal lobe epilepsy model","alternate_titles":[],"description":"Label-free Proteomic profile of the dentate gyrus (dorsal and ventral) and CA3 (dorsal and ventral) microdissected from the hippocampus of the pilocarpine model of Mesial Temporal Lobe Epilepsy.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. 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Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Temporal_Lobe_Epilepsy","name":"Temporal Lobe Epilepsy","kind":"Disorder","source_path":"kb/disorders/Temporal_Lobe_Epilepsy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Temporal_Lobe_Epilepsy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Temporal_Lobe_Epilepsy.html#dataset-massive-msv000094401"}],"context_names":["Temporal Lobe Epilepsy"],"disease_names":["Temporal Lobe Epilepsy"],"disease_name":"Temporal Lobe Epilepsy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Temporal_Lobe_Epilepsy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Temporal_Lobe_Epilepsy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Temporal_Lobe_Epilepsy.html#dataset-massive-msv000094401"]},{"id":"dataset:massive:msv000094418","accession":"massive:MSV000094418","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000094418","title":"Comprehensive metabolomic/lipidomic characterization of patients with mitochondrial ATP synthase, short-chain acyl-CoA dehydrogenase and combined variant deficiencies","alternate_titles":[],"description":"Targeted metabolomics, organic acids, and lipidomics (LC-MS/MS) of serum and urine from SCAD-deficient patients (n=11), ATP-synthase-deficient, combined, and control groups, showing glycerophospholipid/sphingolipid depletion alongside butyrylcarnitine elevations — membrane and complex-lipid remodeling beyond the diagnostic acylcarnitine signature.","alternate_descriptions":[],"data_types":["METABOLOMICS"],"data_type_labels":["Metabolite profiling"],"data_type_label":"Metabolite profiling","organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:41477503"],"publication_contexts":[{"context_id":"disorder:SCAD_Deficiency","publication":"PMID:41477503"}],"publication":"PMID:41477503","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/41477503","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Organism: human (serum and urine). MassIVE MSV000094418 (DOI 10.25345/C5D50G81T)."],"contexts":[{"id":"disorder:SCAD_Deficiency","name":"Short-Chain Acyl-CoA Dehydrogenase Deficiency","kind":"Disorder","source_path":"kb/disorders/SCAD_Deficiency.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/SCAD_Deficiency.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Short-Chain_Acyl-CoA_Dehydrogenase_Deficiency.html#dataset-massive-msv000094418"}],"context_names":["Short-Chain Acyl-CoA Dehydrogenase Deficiency"],"disease_names":["Short-Chain Acyl-CoA Dehydrogenase Deficiency"],"disease_name":"Short-Chain Acyl-CoA Dehydrogenase Deficiency","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/SCAD_Deficiency.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/SCAD_Deficiency.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Short-Chain_Acyl-CoA_Dehydrogenase_Deficiency.html#dataset-massive-msv000094418"]},{"id":"dataset:massive:msv000094494","accession":"massive:MSV000094494","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000094494","title":"Chikungunya virus glycoprotein targeting of host factors increases viral fitness in human macrophage","alternate_titles":[],"description":"Proteomic analysis of Chikungunya virus E1 and E2 interacting proteins during macrophage infection","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. 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Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Chikungunya","name":"Chikungunya","kind":"Disorder","source_path":"kb/disorders/Chikungunya.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chikungunya.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chikungunya.html#dataset-massive-msv000094494"}],"context_names":["Chikungunya"],"disease_names":["Chikungunya"],"disease_name":"Chikungunya","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chikungunya.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chikungunya.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chikungunya.html#dataset-massive-msv000094494"]},{"id":"dataset:massive:msv000094806","accession":"massive:MSV000094806","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000094806","title":"Proteomic profiling of bronchoalveolar lavage fluid uncovers unique protein clusters linked to survival in idiopathic pulmonary fibrosis and interstitial pneumonia with autoimmune features","alternate_titles":[],"description":"This study aimed to delineate molecular phenotypes of the lung microenvironment across idiopathic interestitial pneumonias, namely interstitial pneumonia with autoimmune features (IPAF)and idiopathic pulmonary fibrosis (IPF) through proteomic analysis of bronchoalveolar lavage fluid (BALF).","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. 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Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Idiopathic_Pulmonary_Fibrosis","name":"Idiopathic Pulmonary Fibrosis","kind":"Disorder","source_path":"kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Idiopathic_Pulmonary_Fibrosis.html#dataset-massive-msv000094806"}],"context_names":["Idiopathic Pulmonary Fibrosis"],"disease_names":["Idiopathic Pulmonary Fibrosis"],"disease_name":"Idiopathic Pulmonary Fibrosis","same_context_model_ids":["model:kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml:Immune-cell-free AT2-lineage and fibroblast organoids","model:kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml:Microengineered alveolar array lung-on-chip with breathing mechanics"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Idiopathic_Pulmonary_Fibrosis.html#dataset-massive-msv000094806"]},{"id":"dataset:massive:msv000095097","accession":"massive:MSV000095097","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000095097","title":"Lipidomics-based algorithms can enhance prediction of obstructive coronary artery disease","alternate_titles":[],"description":"Lipidomics-based algorithms can enhance prediction of obstructive coronary artery disease","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Coronary Artery Disease\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Coronary_Artery_Disease","name":"Coronary Artery Disease","kind":"Disorder","source_path":"kb/disorders/Coronary_Artery_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Coronary_Artery_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Coronary_Artery_Disease.html#dataset-massive-msv000095097"}],"context_names":["Coronary Artery Disease"],"disease_names":["Coronary Artery Disease"],"disease_name":"Coronary Artery Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Coronary_Artery_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Coronary_Artery_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Coronary_Artery_Disease.html#dataset-massive-msv000095097"]},{"id":"dataset:massive:msv000095560","accession":"massive:MSV000095560","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000095560","title":"Lipid Supplements Protect Dilated Cardiomyopathy","alternate_titles":[],"description":"Lipid (Plasmalogen) levels can be modulated via a dietary supplement called alkylglycerols (AG) which has demonstrated benefits in some disease settings. However, its therapeutic potential in cardiomyopathy remains unknown. This study explored an optimized AG supplement in restoring plasmalogen levels and attenuate cardiac dysfunction/pathology. Here, we placed a cardiac-specific transgenic cardiomyopathy mouse model, with cardiac function and molecular landscape assessed.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Dilated Cardiomyopathy\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Dilated_Cardiomyopathy","name":"Dilated Cardiomyopathy","kind":"Disorder","source_path":"kb/disorders/Dilated_Cardiomyopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dilated_Cardiomyopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy.html#dataset-massive-msv000095560"}],"context_names":["Dilated Cardiomyopathy"],"disease_names":["Dilated Cardiomyopathy"],"disease_name":"Dilated Cardiomyopathy","same_context_model_ids":["model:kb/disorders/Dilated_Cardiomyopathy.yaml:Patient-specific TNNT2 R173W iPSC-derived cardiomyocytes (Clinical Trials in a Dish)"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Dilated_Cardiomyopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Dilated_Cardiomyopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy.html#dataset-massive-msv000095560"]},{"id":"dataset:massive:msv000095776","accession":"massive:MSV000095776","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000095776","title":"Effects of Navitoclax and Venetoclax on changes in the proteome of mouse pancreas in a mouse model of chronic pancreatitis","alternate_titles":[],"description":"Effects of two Bcl-2 protein inhibitors Navitoclax and Venetoclax on changes in the proteome of the mouse pancreas (Mus musculus C57BL6/J, males) in a mouse model of cerulein-induced chronic pancreatitis.","alternate_descriptions":[],"data_types":["PROTEOMICS"],"data_type_labels":["Protein expression profiling"],"data_type_label":"Protein expression profiling","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Chronic Pancreatitis\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Chronic_Pancreatitis","name":"Chronic Pancreatitis","kind":"Disorder","source_path":"kb/disorders/Chronic_Pancreatitis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Pancreatitis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chronic_Pancreatitis.html#dataset-massive-msv000095776"}],"context_names":["Chronic Pancreatitis"],"disease_names":["Chronic Pancreatitis"],"disease_name":"Chronic Pancreatitis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chronic_Pancreatitis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chronic_Pancreatitis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chronic_Pancreatitis.html#dataset-massive-msv000095776"]},{"id":"dataset:massive:msv000096235","accession":"massive:MSV000096235","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000096235","title":"NOTCH3 missense variants cause familial partial lipodystrophy","alternate_titles":[],"description":"Molecular defects in some ultra-rare subtypes of familial lipodystrophies remain unidentified. We identified novel NOTCH3 heterozygous variants in familial partial lipodystrophy (FPL) pedigrees. All variants were clustered in the heterodimerization domain of the negative regulatory region of NOTCH3. Proteomics of skin fibroblasts revealed significantly higher RNA expression of NOTCH3 and activation of widespread senescence pathways in the FPL patients versus controls.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Familial Partial Lipodystrophy\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Familial_Partial_Lipodystrophy","name":"Familial Partial Lipodystrophy","kind":"Disorder","source_path":"kb/disorders/Familial_Partial_Lipodystrophy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Familial_Partial_Lipodystrophy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Familial_Partial_Lipodystrophy.html#dataset-massive-msv000096235"}],"context_names":["Familial Partial Lipodystrophy"],"disease_names":["Familial Partial Lipodystrophy"],"disease_name":"Familial Partial Lipodystrophy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Familial_Partial_Lipodystrophy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Familial_Partial_Lipodystrophy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Familial_Partial_Lipodystrophy.html#dataset-massive-msv000096235"]},{"id":"dataset:massive:msv000096452","accession":"massive:MSV000096452","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000096452","title":"Schistosomiasis Metabolites Mining by SPME Dataset","alternate_titles":[],"description":"Data was acquired on schistosomiasis infected samples (Mohembo, Ngarange, Sekondomboro and Xakau) and control samples (Sepopa).","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Schistosomiasis\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Schistosomiasis","name":"Schistosomiasis","kind":"Disorder","source_path":"kb/disorders/Schistosomiasis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Schistosomiasis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Schistosomiasis.html#dataset-massive-msv000096452"}],"context_names":["Schistosomiasis"],"disease_names":["Schistosomiasis"],"disease_name":"Schistosomiasis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Schistosomiasis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Schistosomiasis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Schistosomiasis.html#dataset-massive-msv000096452"]},{"id":"dataset:massive:msv000096486","accession":"massive:MSV000096486","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000096486","title":"Ontogeny independent expression of LPCAT2 in granuloma macrophages during experimental visceral leishmaniasis","alternate_titles":[],"description":"Proteomic data relating to: Ontogeny independent expression of LPCAT2 in granuloma macrophages during experimental visceral leishmaniasis","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. 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Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Leishmaniasis","name":"Leishmaniasis","kind":"Disorder","source_path":"kb/disorders/Leishmaniasis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Leishmaniasis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Leishmaniasis.html#dataset-massive-msv000096486"}],"context_names":["Leishmaniasis"],"disease_names":["Leishmaniasis"],"disease_name":"Leishmaniasis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Leishmaniasis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Leishmaniasis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Leishmaniasis.html#dataset-massive-msv000096486"]},{"id":"dataset:massive:msv000096636","accession":"massive:MSV000096636","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000096636","title":"Comprehensive Metabolomic Profiling of Osteoarthritis Unraveling Sexually Dimorphic Patterns","alternate_titles":[],"description":"Osteoarthritis (OA) is a chronic disease characterized by high morbidity, affecting multiple body systems and associated with systemic metabolic disorders. The clinical features of OA exhibit significant sexual dimorphism. However, the specific metabolic characteristics underlying this difference remain incompletely understood, with a notable lack of molecular risk factors related to OA. In this study, we established a cohort of 60 OA cases comprising different genders.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Osteoarthritis\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Osteoarthritis","name":"Osteoarthritis","kind":"Disorder","source_path":"kb/disorders/Osteoarthritis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Osteoarthritis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Osteoarthritis.html#dataset-massive-msv000096636"}],"context_names":["Osteoarthritis"],"disease_names":["Osteoarthritis"],"disease_name":"Osteoarthritis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Osteoarthritis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Osteoarthritis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Osteoarthritis.html#dataset-massive-msv000096636"]},{"id":"dataset:massive:msv000096814","accession":"massive:MSV000096814","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000096814","title":"Altered Cerebrospinal Fluid Proteins in Smith-Lemli-Opitz Syndrome","alternate_titles":[],"description":"Smith-Lemli-Opitz Syndrome (SLOS) is a rare, autosomal recessive, neurocognitive disorder caused by mutations in the 7-dehydrocholesterol reductase gene (DHCR7), leading to impaired cholesterol biosynthesis. The biochemical results of these defects include accumulation of the cholesterol precursor, 7-dehydrocholesterol (7DHC), and reduced cholesterol. Individuals with SLOS present with a spectrum of developmental anomalies and neurocognitive impairments.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Smith-Lemli-Opitz syndrome\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Smith-Lemli-Opitz_syndrome","name":"Smith-Lemli-Opitz syndrome","kind":"Disorder","source_path":"kb/disorders/Smith-Lemli-Opitz_syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Smith-Lemli-Opitz_syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Smith-Lemli-Opitz_syndrome.html#dataset-massive-msv000096814"}],"context_names":["Smith-Lemli-Opitz syndrome"],"disease_names":["Smith-Lemli-Opitz syndrome"],"disease_name":"Smith-Lemli-Opitz syndrome","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Smith-Lemli-Opitz_syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Smith-Lemli-Opitz_syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Smith-Lemli-Opitz_syndrome.html#dataset-massive-msv000096814"]},{"id":"dataset:massive:msv000096887","accession":"massive:MSV000096887","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000096887","title":"Chikungunya replication and infection is dependent upon and alters cellular hexosylceramide levels in Vero cells","alternate_titles":[],"description":"Chikungunya virus (CHIKV), a mosquito-borne alphavirus, causes significant global mor-bidity, including fever, rash, and persistent arthralgia. Utilizing untargeted lipidomics, we investi-gated how CHIKV infection alters host cell lipid metabolism in Vero cells. CHIKV infection induced marked catabolism of hexosylceramides, reducing their levels while increasing ceramide byprod-ucts. Functional studies revealed a reliance on fatty acid synthesis, ?-oxidation, and glycosphin-golipid biosynthesis.","alternate_descriptions":[],"data_types":["METABOLOMICS"],"data_type_labels":["Metabolite profiling"],"data_type_label":"Metabolite profiling","organisms":[{"id":"NCBITaxon:60711","label":"Chlorocebus sabaeus","display_label":"African green monkey","url":"http://purl.obolibrary.org/obo/NCBITaxon_60711"}],"organism_labels":["Chlorocebus sabaeus"],"organism_label":"Chlorocebus sabaeus","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Chikungunya\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Chikungunya","name":"Chikungunya","kind":"Disorder","source_path":"kb/disorders/Chikungunya.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chikungunya.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Chikungunya.html#dataset-massive-msv000096887"}],"context_names":["Chikungunya"],"disease_names":["Chikungunya"],"disease_name":"Chikungunya","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Chikungunya.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Chikungunya.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Chikungunya.html#dataset-massive-msv000096887"]},{"id":"dataset:massive:msv000097297","accession":"massive:MSV000097297","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000097297","title":"Pathogenesis of focal segmental glomerulosclerosis and minimal change disease","alternate_titles":[],"description":"Podocyte injury is the hallmark of both focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) and is ultimately reflected in foot process effacement proteinuria. Triggers and pathogenic pathways leading to podocyte cytoskeleton rearrangements are however incompletely explained. Here, we aimed to contribute to the understanding of these pathways using tissue bottom-up proteomic profiling of laser capture micro dissected glomeruli from MCD and FSGS.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Focal Segmental Glomerulosclerosis\"). Retrieved 2026-08-02.","Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Minimal Change Disease\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Focal_Segmental_Glomerulosclerosis","name":"Focal Segmental Glomerulosclerosis","kind":"Disorder","source_path":"kb/disorders/Focal_Segmental_Glomerulosclerosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Focal_Segmental_Glomerulosclerosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Focal_Segmental_Glomerulosclerosis.html#dataset-massive-msv000097297"},{"id":"disorder:Minimal_Change_Disease","name":"Minimal Change Disease","kind":"Disorder","source_path":"kb/disorders/Minimal_Change_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Minimal_Change_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Minimal_Change_Disease.html#dataset-massive-msv000097297"}],"context_names":["Focal Segmental Glomerulosclerosis","Minimal Change Disease"],"disease_names":["Focal Segmental Glomerulosclerosis","Minimal Change Disease"],"disease_name":"Focal Segmental Glomerulosclerosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Focal_Segmental_Glomerulosclerosis.yaml","kb/disorders/Minimal_Change_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Focal_Segmental_Glomerulosclerosis.yaml","https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Minimal_Change_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Focal_Segmental_Glomerulosclerosis.html#dataset-massive-msv000097297","https://dismech.monarchinitiative.org/pages/disorders/Minimal_Change_Disease.html#dataset-massive-msv000097297"]},{"id":"dataset:massive:msv000097902","accession":"massive:MSV000097902","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000097902","title":"Proteomics analysis of Rheumatoid arthritis","alternate_titles":[],"description":"The study aimed to identify proteins associated with rheumatoid arthritis. Dysregulated proteins were linked to inflammation, immune response and oxidative stress.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Rheumatoid Arthritis\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Rheumatoid_Arthritis","name":"Rheumatoid Arthritis","kind":"Disorder","source_path":"kb/disorders/Rheumatoid_Arthritis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rheumatoid_Arthritis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Rheumatoid_Arthritis.html#dataset-massive-msv000097902"}],"context_names":["Rheumatoid Arthritis"],"disease_names":["Rheumatoid Arthritis"],"disease_name":"Rheumatoid Arthritis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Rheumatoid_Arthritis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Rheumatoid_Arthritis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Rheumatoid_Arthritis.html#dataset-massive-msv000097902"]},{"id":"dataset:massive:msv000098032","accession":"massive:MSV000098032","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000098032","title":"Markers of neutrophil degranulation in the lung microenvironment linked to idiopathic pulmonary fibrosis severity and survival","alternate_titles":[],"description":"Idiopathic pulmonary fibrosis (IPF) leads to progressive loss of lung function and mortality. Understanding mechanisms and markers of lung injury in IPF is paramount to improving outcomes for these patients. Despite the lack of systemic involvement in IPF, many analyses focus on identifying circulating prognostic markers. Using a proteomic discovery method followed by ELISA confirmation in multiple cohorts we explored novel markers of IPF survival in bronchoalveolar lavage fluid (BALF)","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Idiopathic Pulmonary Fibrosis\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Idiopathic_Pulmonary_Fibrosis","name":"Idiopathic Pulmonary Fibrosis","kind":"Disorder","source_path":"kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Idiopathic_Pulmonary_Fibrosis.html#dataset-massive-msv000098032"}],"context_names":["Idiopathic Pulmonary Fibrosis"],"disease_names":["Idiopathic Pulmonary Fibrosis"],"disease_name":"Idiopathic Pulmonary Fibrosis","same_context_model_ids":["model:kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml:Immune-cell-free AT2-lineage and fibroblast organoids","model:kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml:Microengineered alveolar array lung-on-chip with breathing mechanics"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Idiopathic_Pulmonary_Fibrosis.html#dataset-massive-msv000098032"]},{"id":"dataset:massive:msv000098357","accession":"massive:MSV000098357","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000098357","title":"Proteomic Profiling of Serum Exosomes from Patients with Metastatic Gastric Cancer","alternate_titles":[],"description":"Clinical management of metastatic gastric cancer (mGC) remains a major challenge due to a lack of specific biomarkers and effective therapeutic targets. Recently, accumulating evidence has suggested that exosomes play an essential role in cancer metastasis and can be an excellent reservoir of novel biomarkers and candidate therapeutic targets for cancer. Therefore, in this study, we aimed to reveal the proteomic profile of mGC-derived exosomes.Exosomes were isolated from pooled serum samples of 20 mGC patients and 40 healthy controls (HCs) by ultracentrifugation.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Metastatic Gastric Cancer\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Gastric_Adenocarcinoma","name":"Gastric Adenocarcinoma","kind":"Disorder","source_path":"kb/disorders/Gastric_Adenocarcinoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Gastric_Adenocarcinoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Gastric_Adenocarcinoma.html#dataset-massive-msv000098357"}],"context_names":["Gastric Adenocarcinoma"],"disease_names":["Gastric Adenocarcinoma"],"disease_name":"Gastric Adenocarcinoma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Gastric_Adenocarcinoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Gastric_Adenocarcinoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Gastric_Adenocarcinoma.html#dataset-massive-msv000098357"]},{"id":"dataset:massive:msv000098375","accession":"massive:MSV000098375","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000098375","title":"Comparison of proteome composition of serum enriched in extracellular vesicles isolated from polycythemia vera patients and healthy controls","alternate_titles":[],"description":"Extracellular vesicles (EVs), e.g., exosomes and microvesicles, are one of the main networks of intercellular communication. In myeloproliferative disorders, such as polycythemia vera (PV), excess of EVs originating from overabundant blood cells can directly contribute to thrombosis through their procoagulant activity. However, proteomic composition of these vesicles in PV patients has not been investigated before. In this work, we examined proteomic composition of serum exosomes of PV patients in comparison to healthy controls.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Polycythemia Vera\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Polycythemia_Vera","name":"Polycythemia Vera","kind":"Disorder","source_path":"kb/disorders/Polycythemia_Vera.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Polycythemia_Vera.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Polycythemia_Vera.html#dataset-massive-msv000098375"}],"context_names":["Polycythemia Vera"],"disease_names":["Polycythemia Vera"],"disease_name":"Polycythemia Vera","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Polycythemia_Vera.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Polycythemia_Vera.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Polycythemia_Vera.html#dataset-massive-msv000098375"]},{"id":"dataset:massive:msv000099209","accession":"massive:MSV000099209","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000099209","title":"Plasma Proteomics from Subjects with Abdominal Aortic Aneurysm","alternate_titles":[],"description":"plasma was collected from subjects with diagnosed abdominal aortic aneurysm","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Abdominal Aortic Aneurysm\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Abdominal_Aortic_Aneurysm","name":"Abdominal Aortic Aneurysm","kind":"Disorder","source_path":"kb/disorders/Abdominal_Aortic_Aneurysm.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Abdominal_Aortic_Aneurysm.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Abdominal_Aortic_Aneurysm.html#dataset-massive-msv000099209"}],"context_names":["Abdominal Aortic Aneurysm"],"disease_names":["Abdominal Aortic Aneurysm"],"disease_name":"Abdominal Aortic Aneurysm","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Abdominal_Aortic_Aneurysm.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Abdominal_Aortic_Aneurysm.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Abdominal_Aortic_Aneurysm.html#dataset-massive-msv000099209"]},{"id":"dataset:massive:msv000099396","accession":"massive:MSV000099396","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000099396","title":"Metabolomic data of ALMS1 WT and ALMS1 KO mice before and after symptoms of Alstrom syndrome","alternate_titles":[],"description":"RAW metabolomics data from Mus musculus liver, plasma and WAT used in - Identification of ACBP as a potential target in ciliopathic obesity through multi-omics network analysis. The dataset includes files from ALMS1 KO and WT mice (young and adult)","alternate_descriptions":[],"data_types":["METABOLOMICS"],"data_type_labels":["Metabolite profiling"],"data_type_label":"Metabolite profiling","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Alstrom Syndrome\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Alstrom_Syndrome","name":"Alstrom Syndrome","kind":"Disorder","source_path":"kb/disorders/Alstrom_Syndrome.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alstrom_Syndrome.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Alstrom_Syndrome.html#dataset-massive-msv000099396"}],"context_names":["Alstrom Syndrome"],"disease_names":["Alstrom Syndrome"],"disease_name":"Alstrom Syndrome","same_context_model_ids":["model:kb/disorders/Alstrom_Syndrome.yaml:ALMS1-knockout human iPSC-derived cardiomyocytes"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Alstrom_Syndrome.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alstrom_Syndrome.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Alstrom_Syndrome.html#dataset-massive-msv000099396"]},{"id":"dataset:massive:msv000100818","accession":"massive:MSV000100818","repository":"Massive","accession_url":"https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=MSV000100818","title":"Preclinical evaluation of waste-derived pomegranate extract (PWE) as potential preventing and therapeutic for benign prostatic hyperplasia","alternate_titles":[],"description":"This dataset contains LC-MS/MS proteomics data from liver and prostate tissues of Rattus norvegicus. Rats were treated with testosterone to model benign prostatic hyperplasia (BPH) and subsequently with pomegranate waste extract (PWE) to assess its effect on the tissue proteome.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Benign Prostatic Hyperplasia\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Benign_Prostatic_Hyperplasia","name":"Benign Prostatic Hyperplasia","kind":"Disorder","source_path":"kb/disorders/Benign_Prostatic_Hyperplasia.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Benign_Prostatic_Hyperplasia.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Benign_Prostatic_Hyperplasia.html#dataset-massive-msv000100818"}],"context_names":["Benign Prostatic Hyperplasia"],"disease_names":["Benign Prostatic Hyperplasia"],"disease_name":"Benign Prostatic Hyperplasia","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Benign_Prostatic_Hyperplasia.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Benign_Prostatic_Hyperplasia.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Benign_Prostatic_Hyperplasia.html#dataset-massive-msv000100818"]},{"id":"dataset:metabolights:mtbls10743","accession":"metabolights:MTBLS10743","repository":"Metabolights","accession_url":"https://www.ebi.ac.uk/metabolights/MTBLS10743","title":"Metabolomic Changes in Idiopathic and GBA1 Parkinson’s Disease","alternate_titles":[],"description":"Mass spectrometry metabolomics comparing idiopathic Parkinson's disease and GBA1-associated Parkinson's disease cohorts with controls.","alternate_descriptions":[],"data_types":["METABOLOMICS"],"data_type_labels":["Metabolite profiling"],"data_type_label":"Metabolite profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":["idiopathic Parkinson's disease","GBA1-associated Parkinson's disease","healthy controls"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[{"statement":"Metabolomic signatures differ between GBA1-PD and idiopathic PD in sebum and serum with good specificity and sensitivity.","evidence":[{"reference":"metabolights:MTBLS10743","reference_url":"https://www.ebi.ac.uk/metabolights/MTBLS10743","reference_title":"Metabolomic Changes in Idiopathic and GBA1 Parkinson's Disease","supports":"SUPPORT","evidence_source":null,"snippet":"Differences in metabolomic signatures were seen between ... GBA1-PD and iPD in sebum and serum with good specificity and sensitivity.","explanation":"The dataset description reports discriminative metabolomic signatures between GBA1-PD and idiopathic PD."}]},{"statement":"Serum pathways implicated include sphingolipid metabolism, amino sugar metabolism and amino acid pathways, while sebum features are hypothesised to be lipid degradation products.","evidence":[{"reference":"metabolights:MTBLS10743","reference_url":"https://www.ebi.ac.uk/metabolights/MTBLS10743","reference_title":"Metabolomic Changes in Idiopathic and GBA1 Parkinson's Disease","supports":"SUPPORT","evidence_source":null,"snippet":"Significant pathways in serum included sphingolipid metabolism, amino sugar metabolism and amino acid pathways, whereas significant features between groups in sebum are hypothesised to be lipid degradation products.","explanation":"The dataset description lists pathway-level differences in serum and hypothesized lipid degradation products in sebum."}]}],"findings_text":["Metabolomic signatures differ between GBA1-PD and idiopathic PD in sebum and serum with good specificity and sensitivity.","Serum pathways implicated include sphingolipid metabolism, amino sugar metabolism and amino acid pathways, while sebum features are hypothesised to be lipid degradation products."],"evidence":[{"reference":"metabolights:MTBLS10743","reference_url":"https://www.ebi.ac.uk/metabolights/MTBLS10743","reference_title":"Metabolomic Changes in Idiopathic and GBA1 Parkinson's Disease","supports":"SUPPORT","evidence_source":null,"snippet":"Here, we use mass spectrometry based metabolomics to analyse serum and sebum samples from 50 genotyped participants and find differences in lipid and sugar regulation, oxidative stress and the production of amino acids and neurotransmitters which distinguish ... GBA1-PD from iPD.","explanation":"Establishes the dataset's serum and sebum metabolomics design distinguishing GBA1-PD from idiopathic PD."},{"reference":"metabolights:MTBLS10743","reference_url":"https://www.ebi.ac.uk/metabolights/MTBLS10743","reference_title":"Metabolomic Changes in Idiopathic and GBA1 Parkinson's Disease","supports":"SUPPORT","evidence_source":null,"snippet":"Differences in metabolomic signatures were seen between ... GBA1-PD and iPD in sebum and serum with good specificity and sensitivity.","explanation":"The dataset description reports discriminative metabolomic signatures between GBA1-PD and idiopathic PD."},{"reference":"metabolights:MTBLS10743","reference_url":"https://www.ebi.ac.uk/metabolights/MTBLS10743","reference_title":"Metabolomic Changes in Idiopathic and GBA1 Parkinson's Disease","supports":"SUPPORT","evidence_source":null,"snippet":"Significant pathways in serum included sphingolipid metabolism, amino sugar metabolism and amino acid pathways, whereas significant features between groups in sebum are hypothesised to be lipid degradation products.","explanation":"The dataset description lists pathway-level differences in serum and hypothesized lipid degradation products in sebum."}],"notes":["Preprint dataset describing metabolic changes in idiopathic vs GBA1 PD."],"contexts":[{"id":"disorder:Parkinsons_Disease","name":"Parkinson's Disease","kind":"Disorder","source_path":"kb/disorders/Parkinsons_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Parkinsons_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Parkinson's_Disease.html#dataset-metabolights-mtbls10743"}],"context_names":["Parkinson's Disease"],"disease_names":["Parkinson's Disease"],"disease_name":"Parkinson's Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Parkinsons_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Parkinsons_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Parkinson's_Disease.html#dataset-metabolights-mtbls10743"]},{"id":"dataset:metabolights:mtbls2266","accession":"metabolights:MTBLS2266","repository":"Metabolights","accession_url":"https://www.ebi.ac.uk/metabolights/MTBLS2266","title":"Metabolomics of sebum reveals lipid dysregulation in Parkinson's disease","alternate_titles":[],"description":"LC-MS sebum metabolomics in Parkinson's disease, including drug-naive and medicated cohorts, compared with well-matched controls to identify lipid pathway alterations.","alternate_descriptions":[],"data_types":["METABOLOMICS"],"data_type_labels":["Metabolite profiling"],"data_type_label":"Metabolite profiling","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[274],"sample_count":274,"conditions":["Parkinson's disease","drug-naive Parkinson's disease","medicated Parkinson's disease","healthy controls"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:33707447"],"publication_contexts":[{"context_id":"disorder:Parkinsons_Disease","publication":"PMID:33707447"}],"publication":"PMID:33707447","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/33707447","publication_status":"Publication recorded","findings":[{"statement":"Sebum metabolomics in PD shows alterations in lipid metabolism pathways, including the carnitine shuttle, sphingolipid metabolism, arachidonic acid metabolism and fatty acid biosynthesis.","evidence":[{"reference":"metabolights:MTBLS2266","reference_url":"https://www.ebi.ac.uk/metabolights/MTBLS2266","reference_title":"Metabolomics of sebum reveals lipid dysregulation in Parkinson's disease","supports":"SUPPORT","evidence_source":null,"snippet":"Pathway enrichment analysis shows alterations in lipid metabolism related to the carnitine shuttle, sphingolipid metabolism, arachidonic acid metabolism and fatty acid biosynthesis.","explanation":"The dataset description reports lipid pathway alterations detected in sebum metabolomics for PD."}]},{"statement":"LC-MS profiling of 274 participants detected metabolites predictive of PD phenotype.","evidence":[{"reference":"metabolights:MTBLS2266","reference_url":"https://www.ebi.ac.uk/metabolights/MTBLS2266","reference_title":"Metabolomics of sebum reveals lipid dysregulation in Parkinson's disease","supports":"SUPPORT","evidence_source":null,"snippet":"We used liquid chromatography-mass spectrometry (LC-MS) to analyse 274 samples from participants (80 drug naïve PD, 138 medicated PD and 56 well matched control subjects) and detected metabolites that could predict PD phenotype.","explanation":"The dataset description specifies LC-MS profiling and the PD/control cohort sizes."}]}],"findings_text":["Sebum metabolomics in PD shows alterations in lipid metabolism pathways, including the carnitine shuttle, sphingolipid metabolism, arachidonic acid metabolism and fatty acid biosynthesis.","LC-MS profiling of 274 participants detected metabolites predictive of PD phenotype."],"evidence":[{"reference":"metabolights:MTBLS2266","reference_url":"https://www.ebi.ac.uk/metabolights/MTBLS2266","reference_title":"Metabolomics of sebum reveals lipid dysregulation in Parkinson's disease","supports":"SUPPORT","evidence_source":null,"snippet":"Here, we use a metabolomics profiling approach to identify changes to lipids in PD observed in sebum, a non-invasively available biofluid.","explanation":"Establishes that the dataset focuses on PD sebum metabolomics."},{"reference":"metabolights:MTBLS2266","reference_url":"https://www.ebi.ac.uk/metabolights/MTBLS2266","reference_title":"Metabolomics of sebum reveals lipid dysregulation in Parkinson's disease","supports":"SUPPORT","evidence_source":null,"snippet":"Pathway enrichment analysis shows alterations in lipid metabolism related to the carnitine shuttle, sphingolipid metabolism, arachidonic acid metabolism and fatty acid biosynthesis.","explanation":"The dataset description reports lipid pathway alterations detected in sebum metabolomics for PD."},{"reference":"metabolights:MTBLS2266","reference_url":"https://www.ebi.ac.uk/metabolights/MTBLS2266","reference_title":"Metabolomics of sebum reveals lipid dysregulation in Parkinson's disease","supports":"SUPPORT","evidence_source":null,"snippet":"We used liquid chromatography-mass spectrometry (LC-MS) to analyse 274 samples from participants (80 drug naïve PD, 138 medicated PD and 56 well matched control subjects) and detected metabolites that could predict PD phenotype.","explanation":"The dataset description specifies LC-MS profiling and the PD/control cohort sizes."}],"notes":["Metabolomics profiling of sebum as a non-invasive biofluid for PD."],"contexts":[{"id":"disorder:Parkinsons_Disease","name":"Parkinson's Disease","kind":"Disorder","source_path":"kb/disorders/Parkinsons_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Parkinsons_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Parkinson's_Disease.html#dataset-metabolights-mtbls2266"}],"context_names":["Parkinson's Disease"],"disease_names":["Parkinson's Disease"],"disease_name":"Parkinson's Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Parkinsons_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Parkinsons_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Parkinson's_Disease.html#dataset-metabolights-mtbls2266"]},{"id":"dataset:metabolomics_workbench:st000020","accession":"metabolomics_workbench:ST000020","repository":"Metabolomics Workbench","accession_url":"https://www.metabolomicsworkbench.org/data/DRCCMetadata.php?Mode=Study&StudyID=ST000020","title":"Biomarker Discovery in Knee Osteoarthritis (I)","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from metabolomics_workbench. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Osteoarthritis\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Osteoarthritis","name":"Osteoarthritis","kind":"Disorder","source_path":"kb/disorders/Osteoarthritis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Osteoarthritis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Osteoarthritis.html#dataset-metabolomics-workbench-st000020"}],"context_names":["Osteoarthritis"],"disease_names":["Osteoarthritis"],"disease_name":"Osteoarthritis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Osteoarthritis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Osteoarthritis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Osteoarthritis.html#dataset-metabolomics-workbench-st000020"]},{"id":"dataset:metabolomics_workbench:st000133","accession":"metabolomics_workbench:ST000133","repository":"Metabolomics Workbench","accession_url":"https://www.metabolomicsworkbench.org/data/DRCCMetadata.php?Mode=Study&StudyID=ST000133","title":"1H NMR Metabolomics Study of Metastatic Melanoma in C57BL/6J Mouse Spleen","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":["METABOLOMICS"],"data_type_labels":["Metabolite profiling"],"data_type_label":"Metabolite profiling","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from metabolomics_workbench. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Metastatic Melanoma\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Cutaneous_Melanoma","name":"Cutaneous Melanoma","kind":"Disorder","source_path":"kb/disorders/Cutaneous_Melanoma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cutaneous_Melanoma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Cutaneous_Melanoma.html#dataset-metabolomics-workbench-st000133"}],"context_names":["Cutaneous Melanoma"],"disease_names":["Cutaneous Melanoma"],"disease_name":"Cutaneous Melanoma","same_context_model_ids":["model:kb/disorders/Cutaneous_Melanoma.yaml:Xmrk-activated melanocytes in three-dimensional dermal collagen"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Cutaneous_Melanoma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Cutaneous_Melanoma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Cutaneous_Melanoma.html#dataset-metabolomics-workbench-st000133"]},{"id":"dataset:metabolomics_workbench:st000199","accession":"metabolomics_workbench:ST000199","repository":"Metabolomics Workbench","accession_url":"https://www.metabolomicsworkbench.org/data/DRCCMetadata.php?Mode=Study&StudyID=ST000199","title":"IDH1 and Glioma knockdown idh1 (part II)","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from metabolomics_workbench. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Glioma\"). Retrieved 2026-08-02."],"contexts":[{"id":"disorder:Glioma","name":"Glioma","kind":"Disorder","source_path":"kb/disorders/Glioma.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Glioma.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Glioma.html#dataset-metabolomics-workbench-st000199"}],"context_names":["Glioma"],"disease_names":["Glioma"],"disease_name":"Glioma","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Glioma.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Glioma.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Glioma.html#dataset-metabolomics-workbench-st000199"]},{"id":"dataset:metabolomics_workbench:st000218","accession":"metabolomics_workbench:ST000218","repository":"Metabolomics Workbench","accession_url":"https://www.metabolomicsworkbench.org/data/DRCCMetadata.php?Mode=Study&StudyID=ST000218","title":"Role of Microbiome in Psoriatic Arthritis (SCFA in PsA)","alternate_titles":[],"description":null,"alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[],"organism_labels":[],"organism_label":null,"sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Located via OmicsDI, which aggregates across omics repositories; this record comes from metabolomics_workbench. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title (\"Psoriatic Arthritis\"). 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Pathway analyses showed significant enrichment for mitochondrial processes, innate immunity, chronic inflammation, and cell cycle. 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This spaceflight multi-omics study identifying mitochondrial stress as a central hub connects spaceflight biology to HCM-relevant mechanisms."}],"notes":[],"contexts":[{"id":"disorder:Hypertrophic_Cardiomyopathy","name":"Hypertrophic Cardiomyopathy","kind":"Disorder","source_path":"kb/disorders/Hypertrophic_Cardiomyopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hypertrophic_Cardiomyopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy.html#dataset-osdr-osd-488"}],"context_names":["Hypertrophic Cardiomyopathy"],"disease_names":["Hypertrophic Cardiomyopathy"],"disease_name":"Hypertrophic Cardiomyopathy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hypertrophic_Cardiomyopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hypertrophic_Cardiomyopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy.html#dataset-osdr-osd-488"]},{"id":"dataset:osdr:osd-530","accession":"osdr:OSD-530","repository":"OSDR","accession_url":"https://osdr.nasa.gov/bio/repo/data/studies/OSD-530","title":"NASA Twins Study multidimensional analysis of year-long human spaceflight","alternate_titles":[],"description":"Integrated multi-omics dataset from the NASA Twins Study comparing one identical twin astronaut during 1-year ISS mission to his ground-based twin. Cardiovascular findings included carotid artery distension and increased intima-media thickness. 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These systemic cardiovascular effects provide context for understanding how spaceflight stress may interact with HCM susceptibility and cardiac remodeling pathways."}],"notes":[],"contexts":[{"id":"disorder:Hypertrophic_Cardiomyopathy","name":"Hypertrophic Cardiomyopathy","kind":"Disorder","source_path":"kb/disorders/Hypertrophic_Cardiomyopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hypertrophic_Cardiomyopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy.html#dataset-osdr-osd-530"}],"context_names":["Hypertrophic Cardiomyopathy"],"disease_names":["Hypertrophic Cardiomyopathy"],"disease_name":"Hypertrophic Cardiomyopathy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hypertrophic_Cardiomyopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hypertrophic_Cardiomyopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy.html#dataset-osdr-osd-530"]},{"id":"dataset:osdr:osd-557","accession":"osdr:OSD-557","repository":"OSDR","accession_url":"https://osdr.nasa.gov/bio/repo/data/studies/OSD-557","title":"RR-9 Mouse Retina Bioimaging: MicroCT, Immunostaining, and Oxidative Stress Markers After 35-Day ISS Spaceflight","alternate_titles":[],"description":"Bioimaging dataset from NASA Rodent Research 9 (SpaceX CRS-12) comprising micro-computed tomography, H&E histology, peanut agglutinin (PNA) immunostaining of cone photoreceptors, and 4-hydroxynonenal (4-HNE) oxidative stress immunofluorescence in retinas of C57BL/6 mice flown aboard the ISS for 35 days. Flight mice showed significant RPE and choroid thinning, cone photoreceptor degradation, and elevated lipid peroxidation markers, paralleling the oxidative RPE injury pathway in Stargardt disease.","alternate_descriptions":[],"data_types":["MULTI_OMICS_PERTURBATION"],"data_type_labels":["Multi Omics Perturbation"],"data_type_label":"Multi Omics Perturbation","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[{"id":"UBERON:0000966","label":"retina","display_label":"retina","url":"http://purl.obolibrary.org/obo/UBERON_0000966"}],"sample_type_labels":["retina"],"sample_counts":[],"sample_count":null,"conditions":["spaceflight (35-day ISS mission)","ground control","vivarium 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spaceflight.","explanation":"Structural thinning of RPE and choroid layers after spaceflight parallels the RPE atrophy seen in ABCA4-deficient retinas."}]},{"statement":"Spaceflight-induced retinal gene expression changes overlap with retinitis pigmentosa-associated genes, suggesting shared photoreceptor vulnerability pathways.","evidence":[{"reference":"PMID:31527661","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/31527661","reference_title":"Spaceflight influences gene expression, photoreceptor integrity, and oxidative stress-related damage in the murine retina.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"Twelve DEGs were associated with retinitis pigmentosa, characterized by dystrophy of the photoreceptor layer rods and cones.","explanation":"Convergence between spaceflight retinal DEGs and inherited photoreceptor dystrophy genes links spaceflight oxidative stress to genetic retinal degeneration mechanisms."}]}],"findings_text":["Spaceflight causes RPE and choroid thinning with elevated oxidative stress markers in mouse retina, mirroring the RPE injury pathway in Stargardt disease.","Spaceflight-induced retinal gene expression changes overlap with retinitis pigmentosa-associated genes, suggesting shared photoreceptor vulnerability pathways."],"evidence":[{"reference":"PMID:31527661","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/31527661","reference_title":"Spaceflight influences gene expression, photoreceptor integrity, and oxidative stress-related damage in the murine retina.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"RNA sequencing detected 600 differentially expressed genes (DEGs) in murine spaceflight retinas, which were enriched for genes related to visual perception, the phototransduction pathway, and numerous retina and photoreceptor phenotype categories.","explanation":"This ISS mouse retina dataset identified 600 DEGs enriched for visual and phototransduction pathways, providing a spaceflight-specific transcriptomic resource relevant to retinal degeneration research including Stargardt disease."},{"reference":"PMID:31527661","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/31527661","reference_title":"Spaceflight influences gene expression, photoreceptor integrity, and oxidative stress-related damage in the murine retina.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"Twelve DEGs were associated with retinitis pigmentosa, characterized by dystrophy of the photoreceptor layer rods and cones.","explanation":"The overlap between spaceflight-induced retinal gene expression changes and inherited photoreceptor dystrophy genes supports this dataset as relevant to understanding environmental modulation of retinal degeneration pathways shared with ABCA4-related disease."},{"reference":"PMID:31527661","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/31527661","reference_title":"Spaceflight influences gene expression, photoreceptor integrity, and oxidative stress-related damage in the murine retina.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"Total retinal, retinal pigment epithelium, and choroid layer thickness were significantly lower after spaceflight.","explanation":"Structural thinning of RPE and choroid layers after spaceflight parallels the RPE atrophy seen in ABCA4-deficient retinas."}],"notes":[],"contexts":[{"id":"disorder:Stargardt_Disease","name":"Stargardt Disease","kind":"Disorder","source_path":"kb/disorders/Stargardt_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Stargardt_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Stargardt_Disease.html#dataset-osdr-osd-557"}],"context_names":["Stargardt Disease"],"disease_names":["Stargardt Disease"],"disease_name":"Stargardt Disease","same_context_model_ids":["model:kb/disorders/Stargardt_Disease.yaml:Patient-derived retinal organoid model","model:kb/disorders/Stargardt_Disease.yaml:STGD1 iPSC-derived RPE disease-in-a-dish model"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Stargardt_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Stargardt_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Stargardt_Disease.html#dataset-osdr-osd-557"]},{"id":"dataset:osdr:osd-568","accession":"osdr:OSD-568","repository":"OSDR","accession_url":"https://osdr.nasa.gov/bio/repo/data/studies/OSD-568","title":"RR-9 Mouse Retina Proteomics: Blood-Retinal Barrier Disruption and Ocular Adaptations After 35-Day ISS Spaceflight","alternate_titles":[],"description":"Proteomic and immunohistochemical dataset from NASA Rodent Research 9 (SpaceX CRS-12) characterizing blood-retinal barrier integrity, apoptosis, and protein expression changes in retinas of C57BL/6 mice after 35-day ISS spaceflight. Key findings include increased aquaporin-4 expression indicating BRB disturbance, elevated PECAM-1, decreased ZO-1 tight junction protein, and significant retinal vascular endothelial apoptosis, with relevance to RPE barrier dysfunction in Stargardt disease.","alternate_descriptions":[],"data_types":["PROTEOMICS"],"data_type_labels":["Protein expression profiling"],"data_type_label":"Protein expression profiling","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[{"id":"UBERON:0000966","label":"retina","display_label":"retina","url":"http://purl.obolibrary.org/obo/UBERON_0000966"}],"sample_type_labels":["retina"],"sample_counts":[],"sample_count":null,"conditions":["spaceflight (35-day ISS mission)","ground control","vivarium control"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:31160660"],"publication_contexts":[{"context_id":"disorder:Stargardt_Disease","publication":"PMID:31160660"}],"publication":"PMID:31160660","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/31160660","publication_status":"Publication recorded","findings":[{"statement":"Spaceflight disrupts blood-retinal barrier integrity through altered tight junction and adhesion molecule expression, with potential relevance to RPE barrier dysfunction in Stargardt disease.","evidence":[{"reference":"PMID:31160660","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/31160660","reference_title":"Characterization of mouse ocular response to a 35-day spaceflight mission: Evidence of blood-retinal barrier disruption and ocular adaptations.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"Immunohistochemical analysis of the retina revealed that an increased expression of aquaporin-4 (AQP-4) in the flight mice compared to controls gave strong indication of disturbance of BRB integrity.","explanation":"AQP-4 upregulation and BRB disruption after spaceflight provide a model for studying RPE barrier compromise relevant to lipofuscin-driven RPE injury in Stargardt disease."}]}],"findings_text":["Spaceflight disrupts blood-retinal barrier integrity through altered tight junction and adhesion molecule expression, with potential relevance to RPE barrier dysfunction in Stargardt disease."],"evidence":[{"reference":"PMID:31160660","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/31160660","reference_title":"Characterization of mouse ocular response to a 35-day spaceflight mission: Evidence of blood-retinal barrier disruption and ocular adaptations.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"Flight group had significant apoptosis in the retina and retinal vascular endothelial cells compared to control groups","explanation":"Retinal vascular endothelial apoptosis after spaceflight demonstrates BRB compromise relevant to understanding RPE barrier dysfunction in inherited retinal dystrophies."},{"reference":"PMID:31160660","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/31160660","reference_title":"Characterization of mouse ocular response to a 35-day spaceflight mission: Evidence of blood-retinal barrier disruption and ocular adaptations.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"Immunohistochemical analysis of the retina revealed that an increased expression of aquaporin-4 (AQP-4) in the flight mice compared to controls gave strong indication of disturbance of BRB integrity.","explanation":"AQP-4 upregulation and BRB disruption after spaceflight provide a model for studying RPE barrier compromise relevant to lipofuscin-driven RPE injury in Stargardt disease."}],"notes":[],"contexts":[{"id":"disorder:Stargardt_Disease","name":"Stargardt Disease","kind":"Disorder","source_path":"kb/disorders/Stargardt_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Stargardt_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Stargardt_Disease.html#dataset-osdr-osd-568"}],"context_names":["Stargardt Disease"],"disease_names":["Stargardt Disease"],"disease_name":"Stargardt Disease","same_context_model_ids":["model:kb/disorders/Stargardt_Disease.yaml:Patient-derived retinal organoid model","model:kb/disorders/Stargardt_Disease.yaml:STGD1 iPSC-derived RPE disease-in-a-dish model"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Stargardt_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Stargardt_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Stargardt_Disease.html#dataset-osdr-osd-568"]},{"id":"dataset:osdr:osd-574","accession":"osdr:OSD-574","repository":"OSDR","accession_url":"https://osdr.nasa.gov/bio/repo/data/studies/OSD-574","title":"Transcriptomic effects on the mouse heart following 30 days on the ISS","alternate_titles":[],"description":"RNA sequencing from hearts of female C57BL/6J mice flown on ISS for 30 days. 1,147 transcripts significantly regulated with activation of MAPK, PI3K-Akt, and GPCR signaling pathways. Cytoskeleton reorganization transcripts were upregulated. Relevant to HCM as MAPK and PI3K-Akt are key hypertrophic signaling pathways in cardiomyopathy.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[{"id":"UBERON:0000948","label":"heart","display_label":"heart","url":"http://purl.obolibrary.org/obo/UBERON_0000948"}],"sample_type_labels":["heart"],"sample_counts":[],"sample_count":null,"conditions":["spaceflight","ground control"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:36830740"],"publication_contexts":[{"context_id":"disorder:Hypertrophic_Cardiomyopathy","publication":"PMID:36830740"}],"publication":"PMID:36830740","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/36830740","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:36830740","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/36830740","reference_title":"Transcriptomic Effects on the Mouse Heart Following 30 Days on the International Space Station.","supports":"SUPPORT","evidence_source":"MODEL_ORGANISM","snippet":"Our analyses showed that 1147 transcripts were significantly regulated after spaceflight. The MAPK, PI3K-Akt, and GPCR signaling pathways were predicted to be activated. Transcripts related to cytoskeleton breakdown and organization were upregulated","explanation":"MAPK and PI3K-Akt signaling pathway activation during spaceflight directly overlaps with known hypertrophic signaling cascades in HCM. Cytoskeletal reorganization is also a hallmark of cardiomyocyte remodeling in HCM."}],"notes":[],"contexts":[{"id":"disorder:Hypertrophic_Cardiomyopathy","name":"Hypertrophic Cardiomyopathy","kind":"Disorder","source_path":"kb/disorders/Hypertrophic_Cardiomyopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hypertrophic_Cardiomyopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy.html#dataset-osdr-osd-574"}],"context_names":["Hypertrophic Cardiomyopathy"],"disease_names":["Hypertrophic Cardiomyopathy"],"disease_name":"Hypertrophic Cardiomyopathy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hypertrophic_Cardiomyopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hypertrophic_Cardiomyopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy.html#dataset-osdr-osd-574"]},{"id":"dataset:osdr:osd-580","accession":"osdr:OSD-580","repository":"OSDR","accession_url":"https://osdr.nasa.gov/bio/repo/data/studies/OSD-580","title":"Transcriptional profiling of heart tissue from mice flown on the RRRM-2 mission","alternate_titles":[],"description":"Bulk RNA-seq from right ventricle tissue of C57BL/6NTac mice flown on ISS for 55-58 days (RRRM-2 mission). Includes old and young mice with flight, ground control, vivarium, and basal groups. 160 female mice total with half euthanized on-orbit. Provides long-duration spaceflight cardiac transcriptome data relevant to age-dependent cardiac remodeling.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[{"id":"UBERON:0002080","label":"heart right ventricle","display_label":"heart right ventricle","url":"http://purl.obolibrary.org/obo/UBERON_0002080"}],"sample_type_labels":["heart right ventricle"],"sample_counts":[],"sample_count":null,"conditions":["spaceflight","ground control","vivarium control","basal"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["DOI: 10.26030/RRQ0-WV29. 160 female mice; half euthanized on-orbit after 55-58 days, half returned live. Includes age as a variable (young vs old mice)."],"contexts":[{"id":"disorder:Hypertrophic_Cardiomyopathy","name":"Hypertrophic Cardiomyopathy","kind":"Disorder","source_path":"kb/disorders/Hypertrophic_Cardiomyopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hypertrophic_Cardiomyopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy.html#dataset-osdr-osd-580"}],"context_names":["Hypertrophic Cardiomyopathy"],"disease_names":["Hypertrophic Cardiomyopathy"],"disease_name":"Hypertrophic Cardiomyopathy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hypertrophic_Cardiomyopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hypertrophic_Cardiomyopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy.html#dataset-osdr-osd-580"]},{"id":"dataset:osdr:osd-737","accession":"osdr:OSD-737","repository":"OSDR","accession_url":"https://osdr.nasa.gov/bio/repo/data/studies/OSD-737","title":"Heart-on-a-chip spaceflight RNA-seq from engineered human heart tissues on ISS","alternate_titles":[],"description":"RNA sequencing from automated heart-on-a-chip engineered human heart tissues (EHTs) flown on ISS for ~1 month. Spaceflight EHTs exhibited reduced twitch forces, increased arrhythmias, sarcomere disruption, and mitochondrial damage. Transcriptomic analyses showed up-regulation of heart failure and oxidative stress pathways with down-regulation of contractility and calcium signaling genes. Relevant to HCM as a model for microgravity-induced cardiac dysfunction including hypertrophic signaling.","alternate_descriptions":[],"data_types":["BULK_RNA_SEQ"],"data_type_labels":["Bulk RNA sequencing"],"data_type_label":"Bulk RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0000948","label":"heart","display_label":"heart","url":"http://purl.obolibrary.org/obo/UBERON_0000948"}],"sample_type_labels":["heart"],"sample_counts":[],"sample_count":null,"conditions":["spaceflight microgravity","ground control"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39312653"],"publication_contexts":[{"context_id":"disorder:Hypertrophic_Cardiomyopathy","publication":"PMID:39312653"}],"publication":"PMID:39312653","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39312653","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:39312653","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/39312653","reference_title":"Spaceflight-induced contractile and mitochondrial dysfunction in an automated heart-on-a-chip platform.","supports":"SUPPORT","evidence_source":"IN_VITRO","snippet":"Spaceflight EHTs exhibited significantly reduced twitch forces, increased incidences of arrhythmias, and increased signs of sarcomere disruption and mitochondrial damage. Transcriptomic analyses showed an up-regulation of genes and pathways associated with metabolic disorders, heart failure, oxidative stress, and inflammation, while genes related to contractility and calcium signaling showed significant down-regulation.","explanation":"Automated EHT platform flown on ISS demonstrates that microgravity induces cardiac dysfunction phenotypes overlapping with HCM pathophysiology, including sarcomere disruption, mitochondrial damage, and altered calcium signaling."}],"notes":["Part of NIH NCATS Tissue Chips in Space program. DOI: 10.26030/t9v3-gx23."],"contexts":[{"id":"disorder:Hypertrophic_Cardiomyopathy","name":"Hypertrophic Cardiomyopathy","kind":"Disorder","source_path":"kb/disorders/Hypertrophic_Cardiomyopathy.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hypertrophic_Cardiomyopathy.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy.html#dataset-osdr-osd-737"}],"context_names":["Hypertrophic Cardiomyopathy"],"disease_names":["Hypertrophic Cardiomyopathy"],"disease_name":"Hypertrophic Cardiomyopathy","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Hypertrophic_Cardiomyopathy.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Hypertrophic_Cardiomyopathy.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Hypertrophic_Cardiomyopathy.html#dataset-osdr-osd-737"]},{"id":"dataset:osdr:osd-804","accession":"osdr:OSD-804","repository":"OSDR","accession_url":"https://osdr.nasa.gov/bio/repo/data/studies/OSD-804","title":"37-Day microgravity exposure in 16-Week female C57BL/6J mice during NASA RR-1 -- bone loss at weight-bearing sites","alternate_titles":[],"description":"MicroCT analysis of femur and vertebrae from mice on the RR-1 NASA Validation Flight (SpaceX-4). Demonstrates significant cancellous and cortical bone loss in femur but not L2 vertebrae after 37 days of microgravity.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:10090","label":"Mus musculus","display_label":"mouse","url":"http://purl.obolibrary.org/obo/NCBITaxon_10090"}],"organism_labels":["Mus musculus"],"organism_label":"Mus musculus","sample_types":[],"sample_type_labels":[],"sample_counts":[],"sample_count":null,"conditions":["spaceflight microgravity","ground control"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":[],"publication_contexts":[],"publication":null,"publication_url":null,"publication_status":"No publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":[],"contexts":[{"id":"disorder:Osteoporosis","name":"Osteoporosis","kind":"Disorder","source_path":"kb/disorders/Osteoporosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Osteoporosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Osteoporosis.html#dataset-osdr-osd-804"}],"context_names":["Osteoporosis"],"disease_names":["Osteoporosis"],"disease_name":"Osteoporosis","same_context_model_ids":["model:kb/disorders/Osteoporosis.yaml:3D bone organoid with coupled osteoblast-osteoclast remodeling","model:kb/disorders/Osteoporosis.yaml:IDG-SW3 osteoblast-to-osteocyte differentiation line","model:kb/disorders/Osteoporosis.yaml:MLO-Y4 osteocyte-like cell line"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Osteoporosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Osteoporosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Osteoporosis.html#dataset-osdr-osd-804"]},{"id":"dataset:pmid:12110406","accession":"PMID:12110406","repository":"PMID","accession_url":"http://www.ncbi.nlm.nih.gov/pubmed/12110406","title":"Osteogenesis imperfecta type VII: an autosomal recessive form of brittle bone disease.","alternate_titles":[],"description":"Foundational clinical, radiological, and histological cohort describing eight individuals with osteogenesis imperfecta type VII from an isolated First Nations community in northern Quebec.","alternate_descriptions":[],"data_types":["PHENOPACKETS"],"data_type_labels":["GA4GH Phenopacket collection (case-level phenotype data)"],"data_type_label":"GA4GH Phenopacket collection (case-level phenotype data)","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[],"sample_type_labels":[],"sample_counts":[8],"sample_count":8,"conditions":["Osteogenesis imperfecta type VII"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:12110406"],"publication_contexts":[{"context_id":"disorder:Osteogenesis_Imperfecta_Type_VII","publication":"PMID:12110406"}],"publication":"PMID:12110406","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/12110406","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:12110406","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/12110406","reference_title":"Osteogenesis imperfecta type VII: an autosomal recessive form of brittle bone disease.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"We report the clinical, radiological, and histological features of four children (age 3.9-8.6 years at last follow-up; all girls) and four adults (age 28-33 years; two women) with a novel form of autosomal recessive OI living in an isolated First Nations community in northern Quebec.","explanation":"Supports this publication as the defining eight-person human phenotype cohort for OI type VII."},{"reference":"PMID:12110406","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/12110406","reference_title":"Osteogenesis imperfecta type VII: an autosomal recessive form of brittle bone disease.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"Histomorphometric analyses of iliac crest bone samples revealed findings similar to OI type I, with decreased cortical width and trabecular number, increased bone turnover, and preservation of the birefringent pattern of lamellar bone.","explanation":"Confirms that the cohort includes structured bone histology data in addition to clinical and radiographic characterization."}],"notes":[],"contexts":[{"id":"disorder:Osteogenesis_Imperfecta_Type_VII","name":"Osteogenesis Imperfecta Type VII","kind":"Disorder","source_path":"kb/disorders/Osteogenesis_Imperfecta_Type_VII.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Osteogenesis_Imperfecta_Type_VII.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Osteogenesis_Imperfecta_Type_VII.html#dataset-pmid-12110406"}],"context_names":["Osteogenesis Imperfecta Type VII"],"disease_names":["Osteogenesis Imperfecta Type VII"],"disease_name":"Osteogenesis Imperfecta Type VII","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Osteogenesis_Imperfecta_Type_VII.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Osteogenesis_Imperfecta_Type_VII.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Osteogenesis_Imperfecta_Type_VII.html#dataset-pmid-12110406"]},{"id":"dataset:pmid:16222184","accession":"PMID:16222184","repository":"PMID","accession_url":"http://www.ncbi.nlm.nih.gov/pubmed/16222184","title":"Clinical manifestations of superior semicircular canal dehiscence","alternate_titles":[],"description":"Clinical cohort dataset from 65 SCDS patients including symptom triggers, audiometric air-bone gaps, VEMP thresholds, and postsurgical outcomes for canal plugging versus resurfacing.","alternate_descriptions":[],"data_types":[],"data_type_labels":[],"data_type_label":null,"organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"Homo 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combine data from the Anorexia Nervosa Genetics Initiative (ANGI)8,9 and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci.","explanation":"The publication reports 72,517 total analyzed cases and controls."},{"reference":"PMID:31308545","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/31308545","reference_title":"Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass 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The original study is a mixed murine + human atlas; only the human lung subset is cited here (evidence_source HUMAN_CLINICAL)."],"contexts":[{"id":"disorder:Idiopathic_Pulmonary_Fibrosis","name":"Idiopathic Pulmonary Fibrosis","kind":"Disorder","source_path":"kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Idiopathic_Pulmonary_Fibrosis.html#dataset-scea-e-curd-126"}],"context_names":["Idiopathic Pulmonary Fibrosis"],"disease_names":["Idiopathic Pulmonary Fibrosis"],"disease_name":"Idiopathic Pulmonary Fibrosis","same_context_model_ids":["model:kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml:Immune-cell-free AT2-lineage and fibroblast organoids","model:kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml:Microengineered alveolar array lung-on-chip with breathing mechanics"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Idiopathic_Pulmonary_Fibrosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Idiopathic_Pulmonary_Fibrosis.html#dataset-scea-e-curd-126"]},{"id":"dataset:scea:e-geod-180759","accession":"scea:E-GEOD-180759","repository":"SCEA","accession_url":"https://www.ebi.ac.uk/gxa/sc/experiments/E-GEOD-180759","title":"Single-nucleus RNA-seq of the demyelinated white-matter lesion edge in chronic active multiple sclerosis","alternate_titles":[],"description":"EBI Single Cell Expression Atlas harmonized re-analysis (194,181 nuclei) of the Absinta et al. 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Defines \"microglia inflamed in MS\" (MIMS) and \"astrocytes inflamed in MS\" glial states with neurodegenerative programming at the chronically inflamed lesion rim, and implicates complement component 1q (C1q) as a mediator of MIMS activation — single-cell resolution of the compartmentalized, smouldering inflammation that underlies progression independent of relapse activity.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"human","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0002316","label":"white matter","display_label":"white matter","url":"http://purl.obolibrary.org/obo/UBERON_0002316"}],"sample_type_labels":["white matter"],"sample_counts":[],"sample_count":null,"conditions":["chronic active multiple sclerosis lesion edge","demyelinated white matter"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["single-nucleus RNA-seq (10x Genomics)"],"platform":"single-nucleus RNA-seq (10x Genomics)","publications":["PMID:34497421"],"publication_contexts":[{"context_id":"disorder:Multiple_Sclerosis","publication":"PMID:34497421"}],"publication":"PMID:34497421","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/34497421","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:34497421","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/34497421","reference_title":"A lymphocyte-microglia-astrocyte axis in chronic active multiple sclerosis.","supports":"SUPPORT","evidence_source":"HUMAN_CLINICAL","snippet":"MRI-informed single-nucleus RNA sequencing to profile the edge of demyelinated white matter lesions at various stages of inflammation","explanation":"Human single-nucleus RNA-seq of the chronic active lesion edge (harmonized as SCEA E-GEOD-180759) resolves the disease-specific microglial (MIMS) and astrocytic states driving compartmentalized inflammation at the paramagnetic rim, a leading mechanism of non-relapsing MS progression."}],"notes":["Aggregator provenance: the harmonized re-analysis is hosted by the EBI Single Cell Expression Atlas (accession E-GEOD-180759); the primary deposit is GEO GSE180759 and the underlying study is Absinta et al., Nature 2021 (PMID:34497421, DOI:10.1038/s41586-021-03892-7). The study additionally used a mouse EAE model for C1q validation; only the human lesion snRNA-seq is cited here (evidence_source HUMAN_CLINICAL)."],"contexts":[{"id":"disorder:Multiple_Sclerosis","name":"Multiple Sclerosis","kind":"Disorder","source_path":"kb/disorders/Multiple_Sclerosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Multiple_Sclerosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Multiple_Sclerosis.html#dataset-scea-e-geod-180759"}],"context_names":["Multiple Sclerosis"],"disease_names":["Multiple Sclerosis"],"disease_name":"Multiple Sclerosis","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Multiple_Sclerosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Multiple_Sclerosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Multiple_Sclerosis.html#dataset-scea-e-geod-180759"]},{"id":"dataset:sra:srp058536","accession":"sra:SRP058536","repository":"SRA","accession_url":"https://www.ncbi.nlm.nih.gov/sra/SRP058536","title":"Whole-genome capture sequences from 25 Babesia microti isolates","alternate_titles":[],"description":"Multiplex hybrid-capture sequence data from 25 B. microti isolates obtained from Ixodes scapularis and human blood across U.S. sampling sites, used to characterize genome-wide diversity and northeastern population structure.","alternate_descriptions":[],"data_types":["WGS"],"data_type_labels":["Whole genome sequencing"],"data_type_label":"Whole genome sequencing","organisms":[{"id":"NCBITaxon:5868","label":"Babesia microti","display_label":"Babesia microti","url":"http://purl.obolibrary.org/obo/NCBITaxon_5868"}],"organism_labels":["Babesia microti"],"organism_label":"Babesia microti","sample_types":[{"id":"NCBITaxon:6945","label":"Ixodes scapularis","display_label":"Ixodes scapularis-derived Babesia microti isolate","url":"http://purl.obolibrary.org/obo/NCBITaxon_6945"},{"id":"UBERON:0000178","label":"blood","display_label":"human-blood-derived Babesia microti isolate","url":"http://purl.obolibrary.org/obo/UBERON_0000178"}],"sample_type_labels":["Ixodes scapularis","blood"],"sample_counts":[25],"sample_count":25,"conditions":["Tick-derived Babesia microti","Human-infecting Babesia microti"],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":["Multiplexed hybrid capture and genome sequencing"],"platform":"Multiplexed hybrid capture and genome sequencing","publications":["PMID:27821055"],"publication_contexts":[{"context_id":"disorder:Babesiosis","publication":"PMID:27821055"}],"publication":"PMID:27821055","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/27821055","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[{"reference":"PMID:27821055","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/27821055","reference_title":"Babesia microti from humans and ticks hold a genomic signature of strong population structure in the United States.","supports":"SUPPORT","evidence_source":"OTHER","snippet":"we used multiplexed hybrid capture of 25 B. microti isolates obtained from I. scapularis and human blood.","explanation":"The publication directly states the dataset design, isolate count, and sources."},{"reference":"PMID:27821055","reference_url":"http://www.ncbi.nlm.nih.gov/pubmed/27821055","reference_title":"Babesia microti from humans and ticks hold a genomic signature of strong population structure in the United States.","supports":"SUPPORT","evidence_source":"OTHER","snippet":"Metadata and sequence data of each sample in this study were submitted to NCBI Short Read Archive","explanation":"The data-availability statement supports public SRA deposition."}],"notes":[],"contexts":[{"id":"disorder:Babesiosis","name":"Babesiosis","kind":"Disorder","source_path":"kb/disorders/Babesiosis.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Babesiosis.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Babesiosis.html#dataset-sra-srp058536"}],"context_names":["Babesiosis"],"disease_names":["Babesiosis"],"disease_name":"Babesiosis","same_context_model_ids":["model:kb/disorders/Babesiosis.yaml:Continuous Babesia duncani culture in human erythrocytes"],"candidate_model_ids":[],"association_basis":"Same disease entry as a NAM","nam_disease_context":"Same disease entry as a NAM","source_paths":["kb/disorders/Babesiosis.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Babesiosis.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Babesiosis.html#dataset-sra-srp058536"]},{"id":"dataset:synapse:syn26223298","accession":"synapse:syn26223298","repository":"Synapse","accession_url":"https://www.synapse.org/#!Synapse:syn26223298","title":"SEA-AD (Seattle Alzheimer's Disease Brain Cell Atlas)","alternate_titles":[],"description":"Multimodal atlas of 84 aged donors spanning the full range of Alzheimer neuropathology, with single-nucleus RNA-seq, ATAC-seq and multiome, MERFISH spatial transcriptomics, and quantitative neuropathology, resolved to 139 molecular cell types across middle temporal gyrus and Brodmann area 9.","alternate_descriptions":[],"data_types":["MULTI_OMICS"],"data_type_labels":["Multi Omics"],"data_type_label":"Multi Omics","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"Homo sapiens","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0016538","label":"temporal cortex","display_label":"temporal cortex","url":"http://purl.obolibrary.org/obo/UBERON_0016538"},{"id":"UBERON:0001870","label":"frontal cortex","display_label":"frontal cortex","url":"http://purl.obolibrary.org/obo/UBERON_0001870"}],"sample_type_labels":["temporal cortex","frontal cortex"],"sample_counts":[84],"sample_count":84,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:39402379"],"publication_contexts":[{"context_id":"disorder:Alzheimer_Disease","publication":"PMID:39402379"}],"publication":"PMID:39402379","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/39402379","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Access is split, and the distinction matters for anyone planning an analysis: the raw FASTQs are controlled (Sage/Synapse data use agreement), but the nuclei-by-gene matrices are openly downloadable and are also served through CELLxGENE and the Allen Brain Cell Atlas. `synapse:` accessions have no open per-record metadata API, so `just verify-datasets` reports this one as UNSUPPORTED rather than OK — that is the expected result, not a failure. This is the only human dataset here with enough nuclei per glial class to give the astrocyte, microglia and oligodendrocyte-progenitor senescence hypotheses a fair test against the excitatory-neuron claim."],"contexts":[{"id":"disorder:Alzheimer_Disease","name":"Alzheimer Disease","kind":"Disorder","source_path":"kb/disorders/Alzheimer_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alzheimer_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Alzheimer_Disease.html#dataset-synapse-syn26223298"}],"context_names":["Alzheimer Disease"],"disease_names":["Alzheimer Disease"],"disease_name":"Alzheimer Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Alzheimer_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alzheimer_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Alzheimer_Disease.html#dataset-synapse-syn26223298"]},{"id":"dataset:synapse:syn60084804","accession":"synapse:syn60084804","repository":"Synapse","accession_url":"https://www.synapse.org/#!Synapse:syn60084804","title":"PsychAD_NPS","alternate_titles":[],"description":"PsychAD single-nucleus RNA-seq of dorsolateral prefrontal cortex from 1,494 donors (about 6.3 million nuclei, 27 cell subclasses and 65 subtypes), with donor-level annotation of Alzheimer diagnosis, Braak stage, clinical dementia rating, cognitive resilience and neuropsychiatric symptoms including depression and agitation. PMID:42778763 analysed the 584 donors carrying Alzheimer-related phenotypes to score phenotype-associated cells.","alternate_descriptions":[],"data_types":["SINGLE_CELL_RNA_SEQ"],"data_type_labels":["Single-cell RNA sequencing"],"data_type_label":"Single-cell RNA sequencing","organisms":[{"id":"NCBITaxon:9606","label":"Homo sapiens","display_label":"Homo sapiens","url":"http://purl.obolibrary.org/obo/NCBITaxon_9606"}],"organism_labels":["Homo sapiens"],"organism_label":"Homo sapiens","sample_types":[{"id":"UBERON:0009834","label":"dorsolateral prefrontal cortex","display_label":"dorsolateral prefrontal cortex","url":"http://purl.obolibrary.org/obo/UBERON_0009834"}],"sample_type_labels":["dorsolateral prefrontal cortex"],"sample_counts":[1494],"sample_count":1494,"conditions":[],"exposure_terms":[],"exposures":[],"gene_terms":[],"genes":[],"platforms":[],"platform":null,"publications":["PMID:42778763"],"publication_contexts":[{"context_id":"disorder:Alzheimer_Disease","publication":"PMID:42778763"}],"publication":"PMID:42778763","publication_url":"http://www.ncbi.nlm.nih.gov/pubmed/42778763","publication_status":"Publication recorded","findings":[],"findings_text":[],"evidence":[],"notes":["Distributed through the AD Knowledge Portal under its data use requirements. The title is the Synapse project name as registered (DataCite 10.7303/syn60084804). As with SEA-AD, `synapse:` accessions have no open per-record metadata API, so `just verify-datasets` reports this one as UNSUPPORTED. Unlike SEA-AD it carries neuropsychiatric-symptom annotation, which makes it the dataset here that can separate depression-associated cell states from the Alzheimer signal within the same donors."],"contexts":[{"id":"disorder:Alzheimer_Disease","name":"Alzheimer Disease","kind":"Disorder","source_path":"kb/disorders/Alzheimer_Disease.yaml","source_yaml_url":"https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alzheimer_Disease.yaml","source_page_url":"https://dismech.monarchinitiative.org/pages/disorders/Alzheimer_Disease.html#dataset-synapse-syn60084804"}],"context_names":["Alzheimer Disease"],"disease_names":["Alzheimer Disease"],"disease_name":"Alzheimer Disease","same_context_model_ids":[],"candidate_model_ids":[],"association_basis":"No association recorded","nam_disease_context":"No association recorded","source_paths":["kb/disorders/Alzheimer_Disease.yaml"],"source_yaml_urls":["https://github.com/monarch-initiative/dismech/blob/775267873aa70936cd42ec5e3eca5fefacebe8df/kb/disorders/Alzheimer_Disease.yaml"],"source_page_urls":["https://dismech.monarchinitiative.org/pages/disorders/Alzheimer_Disease.html#dataset-synapse-syn60084804"]}]}